Novel benzodioxols

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of benzodioxol of the formula (I): wherein R1, R2, R3, R4, R5, R6, R7 and X are given in the description and the invention claim, and to their pharmaceutically acceptable salts. Also, invention relates to pharmaceutical compositions based on compounds of the formula (I) and their using for preparing medicinal agents used in treatment and/or prophylaxis of diseases associated with modulation of CB1 receptors.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

19 cl, 279 ex

 

The present invention relates to new derivatives of benzodioxole, their receipt containing their pharmaceutical compositions and their use as medicines. Active compounds of the present invention are useful for the treatment of obesity and other diseases.

In particular, the present invention relates to compounds of formula (I):

where

R1and R2independently represent unsubstituted phenyl or phenyl which is mono-, di - or tizamidine, independently, hydroxy, lower alkyl, lower alkoxy, PERFLUORO-lower alkyl, PERFLUORO-lower alkoxy, alkanoyl, cyano, nitro or halogen; or R1and R2together with the carbon atom to which they are attached, form a residue 10',11'-dihydro-2,5'-[5H]dibenzo[a,d]cycloheptene;

R3and R4independently represent hydrogen, halogen, hydroxy, lower alkyl, lower alkoxy, PERFLUORO-lower alkyl, alkanoyl or cyano;

R5represents hydrogen, lower alkyl, lower alkylsulfonyl, cycloalkyl-lower alkyl or hydroxy-lower alkyl;

R6is a Y-R8, lower alkyl, lower alkoxy, hydroxy-lower alkyl, lower alkoxy-lower alkyl, lower alkylaminocarbonyl-lower alkyl, heterocyclyl, cycloalkyl, phenyl - or vanillasky alkyl, defenily group may be optionally mono-, di - or tizamidine, independently, lower alkyl, lower alkoxy, halogen, PERFLUORO-lower alkyl, hydroxy, alkanoyl or cyano; or

R6represents hydrogen, when X represents-C(O)- or-SO2-;

or

R5and R6together with the nitrogen atom to which they are attached, form a 4-, 5-, 6 - or 7-membered monocyclic or 8-, 9-, 10 -, or 12-membered bicyclic, saturated or unsaturated heterocyclic ring which may optionally contain one or two other heteroatoms independently selected from O, N and S, where the aforementioned heterocyclic ring optionally is mono-, di - or tizamidine, independently, lower alkyl, lower alkoxycarbonyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, di-lower allylcarbamate, carbamoyl, lower alkylcarboxylic, oxo, dioxo, alkanoyl, amino-lower alkyl, hydroxy, lower alkoxy, halogen, PERFLUORO-lower alkyl, cyano, heteroaryl or phenyl or phenyl-lower alkyl, where the phenyl group may be optionally mono-, di - or tizamidine, independently, lower alkyl, lower alkoxy, halogen, PERFLUORO-lower alkyl, hydroxy, alkanoyl or cyano;

R7represents hydrogen, halogen, lower alkyl or cyano;

R8represents phenyl, cycloalkyl, heterotic the silt or heteroaryl;

X represents a single bond, -CH2-, -C(O)-, -SO2- or-SO2NH-;

Y represents-CH2-, -C(O)-, -NH - or-SO2-;

and their pharmaceutically acceptable salts.

Was allocated to two different subtypes of cannabinoid receptors (CB1and ST2), and both belong to the family of receptor-associated G-protein. Was also described alternative splicing form CB1, CB1Abut she did not show other properties in respect of binding ligand and activation of the receptor compared with CB1(D. Shire, S. Carrillon, M. Kaghad, V. Calandra, M. Rinaldi-Carmona, G. Le Fur, D. Caput, P. Ferrara, J. Biol. Chem. 270 (8) (1995) 3726-31). CB1the receptor is mainly concentrated in the brain, whereas SV2the receptor is predominantly distributed in the peripheral system, primarily in the spleen and cells of the immune system (S. Munro, K.L. Thomas, M. Abu-Shaar, Nature 365 (1993) 61-61). Therefore, to eliminate the side effects required CB1-selective compounds.

Δ9-tetrahydrocannabinol (Δ9-THC) is the main psychoactive compound in the number of cannabis (Y. Gaoni and R. Mechoulam, J. Am. Chem. Soc., 86 (1964) 1646), canabis savita (marijuana), which has long been used in medicine (R. Mechoulam (Ed.) "Cannabinoids as therapeutic Agents", 1986, pp.1-20, CRC Press). Δ9-THC is a non-selective agonist CB1/2receptor and known in the U.S. as dronabinol (arinol ®) for the treatment of vomiting induced by cancer chemotherapy (CIE), and cessation of weight loss in patients with AIDS, by stimulating appetite. In the UK, nablidon (LY-109514, Cesamet®), a synthetic analogue Δ9-THC, is used against CIE (R.G. Pertwee, Pharmaceut. Sci. 3 (11) (1997) 539-545, E.M. Williamson, F.J. Evans, Drugs 60 (6) (2000) 1303-1314).

Anandamide (arachidonoylethanolamide) was discovered as an endogenous ligand (agonist) for CB1(R.G.Pertwee, Curr. Med. Chem., 6 (8) (1999) 635-664; W.A. Devane, L. Hanus, A. Breuer, R.G. Pertwee, L.A. Stevenson, G. Griffin, D. Gibson, A. Mandelbaum, A. Etinger, R. Mechoulam, Science 258 (1992) 1946-9). Anandamide and 2-arachidonoylglycerol (2-AG) modulate negative terminal adenylate cyclase presynaptic nerve and dependent voltage and CA2+channels and activate the internal state of+channel (V. Di Marzo, D.Melck, T. Bisogno, L. De Petrocellis, Trends in Neuroscience 21 (12) (1998) 521-8), thereby affecting the release and/or action of the neurotransmitter, reducing the release of neurotransmitter (A.S. Porter, S. Felder, Pharmacol. Ther., 90 (1) (2001) 45-60).

Anandamide Δ9-THC also increases the need for food using CB1receptor-mediamoo mechanism. CB1selective antagonists block the increasing need for food, associated with the introduction of anandamide (S.M. Williams, T.C. Kirkham, Psychopharmacology 143 (3) (1999) 315-317; S. Felder, E.M. Briley, J. Axelrod, J.. Simpson, K. Mackie, W.A. Devane, Proc. Natl. Acad. Sci. U.S.A.90 (16) (1993) 7656-60), and cause appetite suppression and weight loss (G. Colombo, R. Agabio, G. Diaz, .Lobina, R.Reali, G.L.Gessa, Life Sci. 63 (8) (1998) L113-PL117).

Leptin is the primary signal, by which the hypothalamus perceives hunger and modulates food intake and energy balance. After a temporary food restrictions, mouse entered CB1 receptor is less consumed food in comparison with normal individuals, and the CB1 antagonist SR141716A reduced food intake in normal mice, but not in treated mice. In addition, improper transfer of leptin is associated with elevated levels in the hypothalamus, but not in the cerebral cortex, endocannabinoids in obese db/db and ob/ob mice and Zucker rats. Treatment with leptin in normal rats and ob/ob mice reduces the levels of anandamide and 2-arachidonoylglycerol in the hypothalamus. This discovery showed that endocannabinoids in the hypothalamus may be toning activate SW receptors to maintain food intake and form part of the neural circuitry regulating leptin (V.Di Marzo, S.. Goparaju, L. Wang, J. Liu, S. Bitkai, Jarai Z., F. Fezza, G.I. Miura, R.D. Palmiter, T. Sugiura, G.Kunos, Nature 410 (6830) 822-825).

SR-141716A, a selective CB1 antagonist/inverse agonist is currently undergoing phase III clinical trials for the treatment of obesity. In a double-blind placebo-controlled study, doses of 5, 10 and 20 mg / day, SR 141716 significantly reduces body weight compared with placebo (F. Barth, M. Rinadi-Carmona, M. Arnone, H. Heshmati, G. Le Fur, "cannabinoid chemistry antagonists: From research tools to potential new drugs." Abstracts of Papers, 222nd ACS National Meeting, Chicago, IL, United States, August 26-30, 2001).

Other compounds that can be proposed as antagonists SW receptor and, accordingly, inverse agonists, are aminoalkylindole (AAI; M. Pacheco, S.R. Childers, R. Arnold, F. Casiano, S.J. Ward, J. Pharmacol. Exp. Ther. 257 (1) (1991) 170-183), such as 6-bromo-(WIN54661; F.M. Casiano, R. Arnold, D. Haycock, J. Kuster, S.J. Ward, NIDA Res. Monogr. 105 (1991) 295-6) or 6-improvathon (AM, Hosohata, K., R. Quock, R. Hosohata, T.H.Burkey, A. Makriyannis, P. Consroe, W.R. Roeske, H.I.Yamamura, Life Sci. 61 (1997) 115-118; R. Pertwee, G. Griffin, S. Fernando, X. Li, A. Hill, A. Makriyannis, Life Sci. 56 (23-24) (1995) 1949-55).

Ailment[b]thiophene and benzo[b]furan (LY320135, S. Felder, CA Joyce, E.M. Briley, M. Glass, K.R. Mackie, .J. Fahey, G.J. Cullinan, D.. Hunden, D.W. Johnson, M.O. Chaney, G.A. Koppel, M. Brownstein, J. Pharmacol. Exp. Ther. 284 (1) (1998) 291-7), described in WO 9602248, US 5596106, 3-alkyl-(5,5-diphenyl)imidazolidinedione (M. Kanyonyo, S.J. Govaerts, E., Hermans, J.H. Poupaert, D.M. Lambert, Bioorg. Med. Chem. Lett. 9 (15) (1999) 2233-2236), a 3-alkyl-5-aryleneethynylene (F. Ooms, J. Wouters, O. Oscaro, T.Happaerts, G. Bouchard, P.-A. Carrupt, B. Testa, D.M. Lambert, J. Med. Chem. 45 (9) (2002) 1748-1756), are known to be antagonists CB1receptor, respectively acting as an inverse agonist on the hCB1the receptor. WO 0015609 (FR 2783246-A1), WO 0164634 (FR 2805817-A1), WO 0228346, WO 0164632 (FR 2805818-A1), WO 0164633 (FR 2805810-A1) discloses substituted derivatives of 1-bis(aryl)methyl-azetidine as antagonists CB1. In WO 0170700 described derivative of 4,5-dihydro-1H-piraso is as CB 1antagonists. Some of the patents described bridge and namashikaye 1,5-diphenyl-3-pyrazolecarboxylate derivatives as CB1antagonists/inverse agonists (WO 0132663, WO 0046209, WO 9719063, EP 658546, EP 656354, US 5624941, EP 576357, US 3940418). Have recently been described, various other structural classes as modulators of ST receptor (WO 0158869, WO 0224630).

The aim of the present invention is the provision of a selective, direct antagonists and accordingly inverse agonists SW receptor. Such antagonists/inverse agonists are useful in medicine, especially for treating and/or preventing diseases that are associated with the modulation SW receptors.

Unless otherwise stated, the following definitions illustrate and define the meaning and scope of various terms used to describe the invention.

In this description, the term "lower" denotes the group consisting of from one to six, preferably one to four carbon atoms.

The term "halogen" denotes fluorine, chlorine, bromine and iodine, preferably chlorine, fluorine and bromine, most preferably chlorine and fluorine.

The term "alkyl", alone or in combination with other groups, denotes a branched or linear monovalent saturated aliphatic hydrocarbon radical with one to twenty carbon atoms, preferably with one-pole is adatu carbon atoms, more preferably one to six carbon atoms.

The term "lower alkyl", alone or in combination with other groups, denotes a branched or linear monovalent alkyl radical with one to six carbon atoms, preferably one to four carbon atoms. This term is represented by radicals such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, 3-methylbutyl, n-hexyl, 2-ethylbutyl and the like.

The term "cycloalkyl" refers to a monovalent carbocyclic radical of three to six, preferably three to five carbon atoms. This term is represented by radicals, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.

The term "lower alkylsulfonyl" refers to the group R'-SO2-where R' is a lower alkyl.

The term "lower alkylaryl" refers to the group R'-CO-, where R' is a lower alkyl.

The term "alkoxy" denotes a group R'-O-, where R' represents alkyl. The term "lower alkoxy" denotes a group R'-O-, where R' is a lower alkyl. Examples of the lower alkoxygroup are, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, hexyloxy, where methoxy is particularly preferred.

The term "lower alkoxycarbonyl" refers to the group R'-O-C(O)- where R' is a lower alkyl.

The term "PERFLUORO-lower alkyl" denotes a lower alkyl group, where all the hydrogen atoms of the lower alkyl groups substituted with fluorine. Preferred PERFLUORO-lower alkyl groups are trifluoromethyl, pentafluoroethyl and hexaferrites where trifluoromethyl is particularly preferred.

The term "alkanoyl" refers to a group C(O)-R, where R represents hydrogen or lower alkyl. Examples of alkanoglu are formyl, acetyl, propionyl and the like.

The term "phenyl-lower alkyl" denotes a phenyl group which is attached to the remainder of the molecule through the lower alkylenes group such as methylene, ethylene, propylene or butylene, preferably methylene and ethylene. Preferred phenyl-lower alkyl residues are benzyl and 1-phenylethyl.

The term "amino-lower alkyl" denotes a lower alkyl radical, a substituted amino group.

The term "heterocyclyl" denotes a 5 - or 6-membered saturated heterocyclic residue containing one or two heteroatoms selected from nitrogen, oxygen and sulfur. Examples heterocyclyl residues are morpholino, tetrahydrofuranyl, pyrrolidinyl, piperidinyl and azepane.

The term "heteroaryl" refers to an aromatic monovalent mono - or polycarbocyclic radical having at least one heteroatom selected from N,O and S. Examples of heteroaryl groups are pyridinyl, pyrazinyl and pyrimidinyl. Such heteroaryl residues may be optionally mono-, di - or tizamidine, independently, lower alkoxy, lower alkyl, PERFLUORO-lower alkyl, cyano and alkanols, preferably halogen and PERFLUORO-lower alkyl.

The term "pharmaceutically acceptable salt" includes salts of compounds of formula (I) with inorganic or organic acids, such as hydrochloric acid, Hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, citric acid, formic acid, maleic acid, acetic acid, fumaric acid, succinic acid, tartaric acid, methanesulfonate acid, salicylic acid, p-toluensulfonate acid and the like, which are not toxic to living organisms. The preferred salts with acids are the formats, maleate, citrates, hydrochloride, hydrobromide and salt methanesulfonic acid, where hydrochloride are particularly preferred.

In one embodiment, the present invention relates to compounds of formula (I):

where

R1and R2independently represent unsubstituted phenyl or phenyl which is mono-, di - or tizamidine, independently, hydroxy, lower alkalo is, lower alkoxy, PERFLUORO-lower alkyl, alkanoyl, cyano or halogen;

R3and R4independently represent hydrogen, halogen, hydroxy, lower alkyl, lower alkoxy, PERFLUORO-lower alkyl, alkanoyl or cyano;

R5represents hydrogen or lower alkyl;

R6represents phenyl or phenyl-lower alkyl, where the phenyl group may be optionally mono-, di - or tizamidine, independently, lower alkyl, lower alkoxy, halogen, PERFLUORO-lower alkyl, hydroxy, alkanoyl or cyano; or

R5and R6together with the nitrogen atom to which they are attached, form a 5-, 6 - or 7-membered monocyclic or 9 - or 10-membered bicyclic, saturated or unsaturated heterocyclic ring which may optionally contain one or two other heteroatoms independently selected from O, N and S, where the aforementioned heterocyclic ring is optionally mono-, di - or tizamidine, independently, lower alkyl, lower alkoxycarbonyl, hydroxy-lower alkyl, alkanoyl, amino-lower alkyl, hydroxy, lower alkoxy, halogen, PERFLUORO-lower alkyl, cyano, heteroaryl or phenyl or phenyl-lower alkyl, where the phenyl group may be optionally mono-, di - or tizamidine, independently, lower alkyl, lower alkoxy, halogen, PERFLUORO-issim-alkyl, hydroxy, alkanoyl or cyano;

X represents-CH2-, -C(O)- or-SO2-;

and their pharmaceutically acceptable salts.

In one embodiment, R1and R2represent unsubstituted phenyl. In another embodiment, R1and R2independently represent phenyl, which is mono-, di - or tizamidine, preferably mono - or disubstituted, independently, by hydroxy, lower alkyl, such as methyl, lower alkoxy such as methoxy, PERFLUORO-lower alkyl, such as trifluoromethyl, PERFLUORO-lower alkoxy, such as triptoreline, alkanoyl, cyano, nitro or halogen, such as chlorine, fluorine and bromine.

In another embodiment, R1and R2independently represent unsubstituted phenyl or phenyl which is mono-, di - or tizamidine, preferably mono - or disubstituted, independently, by lower alkyl, such as methyl, lower alkoxy such as methoxy, PERFLUORO-lower alkyl, such as trifluoromethyl, PERFLUORO-lower alkoxy, such as triptoreline, cyano, nitro or halogen, such as chlorine, fluorine and bromine.

In another embodiment, the present invention relates to the compound of formula (I)as described above, where R1and R2independently represent phenyl, which is mono-, di - or tizamidine, n is dependent, hydroxy, lower alkyl, lower alkoxy, PERFLUORO-lower alkyl, alkanoyl, cyano or halogen; preferred substituents of the phenyl residues R1and R2are lower alkyl, such as methyl, lower alkoxy such as methoxy, halogen, such as fluorine and chlorine. Preferably R1and R2independently represent phenyl, which is mono - or disubstituted, independently, by halogen, preferably fluorine, chlorine or bromine, more preferably fluorine or chlorine, or lower alkoxy, preferably methoxy.

Substituted phenyl residues R1and R2preferably substituted, as described above, in the ortho and/or para-position, more preferably in the para-position.

In another embodiment, R1and R2together with the carbon atom to which they are attached, form a residue 10',11'-dihydro-2,5'-[5H]dibenzo[a,d]cycloheptene.

In one embodiment, the present invention relates to the compound of formula (I)as described above, where R3and R4independently represent hydrogen, halogen, hydroxy, lower alkyl, lower alkoxy, PERFLUORO-lower alkyl, alkanoyl or cyano. Preferred residues halogen, R3and R4are fluorine, chlorine and bromine, where fluorine is particularly preferred. Preferred lower alkylene the remainder in R 3and R4represents methyl. Preferred lower alkoxylates in R3and R4represents methoxy. Preferred PERFLUORO-lower alkyl residue in R3and R4represents trifluoromethyl.

In another preferred embodiment, the present invention relates to the compound of formula (I)as described above, where R3and R4independently represent hydrogen, hydroxy or halogen, such as fluorine, chlorine or bromine. Preferred substituents R3and R4are hydrogen and fluorine, where hydrogen is especially preferred.

In one embodiment, the present invention relates to compounds of formula (I)as described above, where R5and R6together with the nitrogen atom to which they are attached, form a 4-, 5-, 6 - or 7-membered monocyclic or 8-, 9-, 10 -, or 12-membered bicyclic, saturated or unsaturated heterocyclic ring which may optionally contain one or two other heteroatoms independently selected from O, N and S, where the aforementioned heterocyclic ring is optionally mono-, di - or tizamidine, preferably mono - or disubstituted, independently, by lower alkyl, lower alkoxycarbonyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, di-lower alkylcarboxylic, what ervamoira, lower alkylcarboxylic, oxo, alkanoyl, amino-lower alkyl, hydroxy, lower alkoxy, halogen, PERFLUORO-lower alkyl, cyano, heteroaryl or phenyl or phenyl-lower alkyl, where the phenyl group may be optionally mono-, di - or tizamidine, preferably mono - or disubstituted, independently, by lower alkyl, lower alkoxy, halogen, PERFLUORO-lower alkyl, hydroxy, alkanoyl or cyano.

In another embodiment, the present invention relates to the compound of formula (I)as described above, where R5and R6together with the nitrogen atom to which they are attached, form a 5-, 6 - or 7-membered monocyclic or 9 - or 10-membered bicyclic, saturated or unsaturated heterocyclic ring which may optionally contain one or two other heteroatoms independently selected from O and N, where the aforementioned heterocyclic ring is optionally mono - or disubstituted, independently, by lower alkyl, lower alkoxycarbonyl, hydroxy-lower alkyl, alkanoyl, hydroxy or phenyl or phenyl-lower alkyl, where the phenyl group may be optionally mono - or disubstituted, independently, lower alkyl, lower alkoxy, halogen or PERFLUORO-lower alkyl.

In the following a preferred embodiment, the present invention relates to connection of the structure of formula (I), as described above, where R5and R6together with the nitrogen atom to which they are attached, form a 5 - or 6-membered monocyclic saturated heterocyclic ring which may optionally contain one other heteroatom selected from O and S, where the aforementioned heterocyclic ring is optionally mono - or disubstituted, independently, by hydroxy or by halogen, such as fluorine.

In one embodiment, the preferred heterocyclic rings obtained from R5and R6together with the nitrogen atom to which they are attached, are piperazinil, morpholino, piperidinyl, piperidine-4-one, pyrrolidinyl, thiomorpholine, azepane, 1,2,3,4-tetrahydro-ethenolysis, 1,2,3,6-tetrahydro-pyridinyl, [1,4]-diazepan, 1,4-dioxa-8-Aza-Spiro[4.5]Dec-8-yl, 2,3,5,6-tetrahydro-[1,2']bipyridinyl-4-yl and 3-hydroxy-8-Aza-bicyclo[3,2,1.]Oct-8-yl, optionally substituted as indicated above, preferably mono-, di - or tizamidine, preferably mono - or disubstituted, independently, by lower alkyl, such as methyl and isopropyl; lower alkoxycarbonyl, such as etoxycarbonyl; hydroxy-lower alkyl, such as hydroxymethyl; lower alkoxy-lower alkyl, such as methoxymethyl; di-lower alkylcarboxylic, such as dimethylcarbamoyl; carbamoyl; lower alkylcarboxylic, such as acetylamino; oxo; di the CSR; alkanoyl, such as formyl; hydroxy; lower alkoxy, such as methoxy, ethoxy; halogen, such as fluorine, PERFLUORO-lower alkyl, such as trifluoromethyl; heteroaryl, such as the unsubstituted pyrazinyl, unsubstituted pyridinyl, pyridinyl, disubstituted by chlorine and/or trifluoromethyl; or phenyl or fininished-alkyl, such as benzyl, where the phenyl group may be optionally mono-, di - or tizamidine, preferably mono - or disubstituted, independently, by lower alkyl, such as methyl, lower alkoxy such as methoxy, halogen, such as chlorine and fluorine, or PERFLUORO-lower alkyl, such as trifluoromethyl.

In another embodiment, preferred heterocyclic rings obtained from R5and R6together with the nitrogen atom to which they are attached, are piperazinil, morpholino, piperidinyl, piperidine-4-one, pyrrolidinyl, 1,2,3,4-tetrahydro-ethenolysis, 1,2,3,6-tetrahydro-pyridinyl, [1,4]-diazepan and 1,4-dioxa-8-Aza-Spiro[4.5]Dec-8-yl, where piperazinil, morpholino and piperidinyl are particularly preferred. In another preferred embodiment, the heterocyclic ring obtained from R5and R6together with the nitrogen atom to which they are attached, is piperidinyl.

Other preferred heterocyclic rings obtained from R5 and R6together with the nitrogen atom to which they are attached, are piperidinyl, morpholino, thiomorpholine and pyrrolidinyl, optionally substituted as indicated above, preferably optionally mono - or disubstituted, independently, by hydroxy or by halogen, such as fluorine. Preferred heterocyclic ring obtained from R5and R6together with the nitrogen atom to which they are attached, is morpholino.

In one embodiment, the heterocyclic ring obtained from R5and R6together with the nitrogen atom to which they are attached, are unsubstituted.

In another embodiment, the heterocyclic ring obtained R5and R6together with the nitrogen atom to which they are attached, are mono-, di - or tizamidine, preferably mono - or disubstituted, independently, by lower alkyl, such as methyl and isopropyl; lower alkoxycarbonyl, such as etoxycarbonyl; hydroxy-lower alkyl, such as hydroxymethyl; lower alkoxy-lower alkyl, such as methoxymethyl; dignissim allylcarbamate, such as dimethylcarbamoyl; carbamoyl; lower alkylcarboxylic, such as acetylamino; oxo; dioxo; alkanoyl, such as formyl; hydroxy; lower alkoxy, such as methoxy, ethoxy; halogen such as fluorine, PERFLUORO-lower alkyl,such as trifluoromethyl; heteroaryl, such as the unsubstituted pyrazinyl, unsubstituted pyridinyl, pyridinyl, disubstituted by chlorine and/or trifluoromethyl; or phenyl or phenyl-lower alkyl, such as benzyl, where the phenyl group may be optionally mono-, di - or tizamidine, preferably mono - or disubstituted, independently, by lower alkyl, such as methyl, lower alkoxy such as methoxy, halogen, such as chlorine and fluorine, or PERFLUORO-lower alkyl, such as trifluoromethyl.

In another embodiment, the heterocyclic ring obtained from R5and R6together with the nitrogen atom to which they are attached, are preferably mono - or disubstituted, independently, stands, propylene, etoxycarbonyl, hydroxymethyl, formyl, hydroxy, unsubstituted pyrazinium, unsubstituted pyridinyl, pyridinyl, disubstituted by chlorine and/or trifluoromethyl; or phenyl or vinylmation, where the phenyl group may be optionally mono - or disubstituted, independently, stands, methoxy, chlorine, fluorine and/or trifluoromethyl.

In a preferred embodiment, the heterocyclic ring obtained from R5and R6together with the nitrogen atom to which they are attached, are optionally mono - or disubstituted, independently, by hydroxy or by halogen, such as fluorine.

Substituted 6-membered, heterotic the practical ring, obtained from R5and R6together with the nitrogen atom to which they are attached, are preferably substituted in position 4 of the ring; substituted 5-membered ring is preferably substituted at position 3 of the ring.

In one embodiment, the present invention relates to compounds of formula (I)as described above, where R5represents hydrogen, lower alkyl, lower alkylsulfonyl, cycloalkyl-lower alkyl or hydroxy-lower alkyl. Preferable lower alkyl residues R5are methyl and ethyl, where methyl is particularly preferred. Preferred lower alkylsulfonyl the remainder R5is n-butylsulfonyl. Preferred cycloalkenyl lower alkyl residue R5is cyclopropylmethyl. Preferred hydroxy-lower alkyl residue R5is 2-hydroxyethyl.

In one embodiment, the present invention relates to compounds of formula (I)as described above, where R6is a Y-R8, lower alkyl, lower alkoxy, hydroxy-lower alkyl, lower alkoxy-lower alkyl, lower allylcarbamate-lower alkyl, heterocyclyl, cycloalkyl, phenyl or phenyl-lower alkyl, where the phenyl group may be optionally mono-, di - or tizamidine, preferably mono - or disa is pregnant independently, lower alkyl, lower alkoxy, halogen, PERFLUORO-lower alkyl, hydroxy, alkanoyl or cyano.

In another embodiment, the present invention relates to compounds of formula (I)as described above, where R6represents lower alkyl, lower alkoxy, hydroxy-lower alkyl, lower alkoxy-lower alkyl, lower allylcarbamate-lower alkyl, heterocyclyl, cycloalkyl, phenyl or phenyl-lower alkyl, where the phenyl group may be optionally mono-, di - or tizamidine, preferably mono - or disubstituted, independently, by lower alkyl, lower alkoxy, halogen, PERFLUORO-lower alkyl, hydroxy, alkanoyl or cyano.

Preferable lower alkyl residues R6are ethyl, n-propyl and isopropyl. Preferred lower alkoxylated R6are tert-butoxy and methoxy. Preferred hydroxy-lower alkyl residue R6is 2-hydroxyethyl. Preferred lower alkoxy-lower alkyl residue R6is methoxyethyl. Preferred heterocyclyl residues R6are morpholino, tetrahydrofuranyl and pyrrolidinyl. Heterocyclyl residues R6preferably pyrrolidinyl the remainder R6may be optionally mono-substituted lower alkoxy-lower alkyl, such as metox is methyl. Preferred cycloalkenyl residues R6are cyclopropyl, cyclobutyl, cyclopentyl and cycloheptyl. Preferred phenyl lower alkyl residues R6are benzyl and phenylethyl. Phenyl groups of the residues phenyl-lower alkyl, R6preferably phenylethylene the remainder R6may be optionally mono-substituted lower alkoxy, such as methoxy. Preferred lower allylcarbamate-lower alkyl residue R6is 2,2-dimethyl-1-methylcarbamoylmethyl.

In another embodiment, the present invention relates to compounds of formula (I)as described above, where R6is a Y-R8.

In another embodiment, the present invention relates to compounds of formula (I)as described above, where R6represents hydrogen, when X represents-C(O)- or-SO2-.

In one embodiment, the present invention relates to the compound of formula (I)as described above, where R7represents hydrogen, cyano, halogen, such as fluorine, or lower alkyl, such as methyl. In another embodiment, R7represents cyano, halogen, such as fluorine, or lower alkyl, such as methyl. In another embodiment, the present invention relates to the compound of formula (I), campisano above, where R7represents hydrogen. Preferably, R7is a halogen, where fluorine is particularly preferred.

In another embodiment, the present invention relates to the compound of formula (I)as described above, where R8represents phenyl, cycloalkyl, heterocyclyl or heteroaryl.

Preferred cycloalkenyl the remainder R8is cyclohexyl. Preferable lower alkyl residues R8are n-propyl, for example, when Y represents-C(O)-, methyl and n-butyl (for example, when Y represents-SO2-). Preferred heterocyclyl residues R8are morpholino, piperidinyl and azepane. Preferred heteroaryl residue R8is pyridinyl.

In a preferred embodiment, R8represents heterocyclyl residue, such as morpholino, piperidinyl and azepane where piperidinyl is especially preferred.

In one embodiment, the present invention relates to compounds of formula (I)as described above, where X represents a single bond, -CH2, -C(O)-, -SO2- or-SO2NH-.

In another embodiment, the present invention relates to compounds of formula (I)as described above, where X is odinary the second link, R3, R4and R7represent hydrogen and R1, R2, R5and R6are as described above.

In a preferred embodiment, the present invention relates to the compound of formula (I)as described above, where X represents-C(O)- or-SO2-where-C(O)- is especially preferred.

In another embodiment, the present invention relates to the compound of formula (I)as described above, where Y represents-CH2-, -C(O)-, -NH - or-SO2-. Preferably, Y is-CH2- or-NH-.

In a preferred embodiment, the present invention relates to compounds of formula (I), where R1and R2independently represent phenyl, which is mono - or disubstituted, independently, by lower alkoxy, such as methoxy, or preferably by halogen, such as fluorine, chlorine and bromine; R3and R4each represents hydrogen; R5and R6together with the nitrogen atom to which they are attached, form a 5 - or 6-membered monocyclic saturated heterocyclic ring which may optionally contain one other heteroatom selected from O and S, such as piperidinyl, morpholino, thiomorpholine and pyrrolidinyl, where the aforementioned heterocyclic ring is optionally mono - or disa is emenim, independently, hydroxy or halogen, such as fluorine; R7is a halogen, such as fluorine; X represents-C(O)-; and their pharmaceutically acceptable salts.

Preferred compounds of General formula (I) selected from the group consisting of:

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-piperidine,

1-(4-chloro-phenyl)-4-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-piperazine,

1-(2,3-dimethyl-phenyl)-4-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-piperazine,

1-(2,4-dichloro-phenyl)-4-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-piperazine,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(4-fluoro-phenyl)-piperazine,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(3-chloro-phenyl)-piperazine,

4-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-morpholine,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-phenyl-piperazine,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-pyrrolidin,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(3-methoxy-phenyl)-piperazine,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(4-methoxy-phenyl)-piperazine,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(2-methoxy-phenyl)-piperazine,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(2-chloro-phenyl)-piperazine,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(2-fluoro-phenyl)-piperazine,

phenethyl-amide 2,2-diphenyl-benzo[1,3]dioxol-5-sulfonic acid,

1-benzo[1,3]dioxol-5-yl-4-(2,2-diphenyl-benzo[1,3]is oxol-5-sulfonyl)-piperazine,

4-benzyl-1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-piperidine,

2-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-1,2,3,4-tetrahydro-isoquinoline,

benzyl-methyl-amide 2,2-diphenyl-benzo[1,3]dioxol-5-sulfonic acid,

benzylated 2,2-diphenyl-benzo[1,3]dioxol-5-sulfonic acid,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-methyl-[1,4]diazepan,

1-(3-chloro-5-trifluoromethyl-pyridine-2-yl)-4-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-[1,4]diazepan,

phenylamide 2,2-diphenyl-benzo[1,3]dioxol-5-sulfonic acid,

[2-(4-methoxy-phenyl)-ethyl]-amide 2,2-diphenyl-benzo[1,3]dioxol-5-sulfonic acid,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-methyl-piperazine,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(4-fluoro-phenyl)-1,2,3,6-tetrahydro-pyridine,

4-(4-chloro-phenyl)-1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-1,2,3,6-tetrahydro-pyridine,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-phenyl-1,2,3,6-tetrahydro-pyridine,

racemic 1-[2-(2-chloro-phenyl)-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

racemic 1-[2-(2-chloro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

racemic 1-[2-(2-chloro-phenyl)-2-p-tolyl-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

racemic 1-[2-(4-chloro-phenyl)-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

racemic 1-[2-(4-chloro-phenyl)-2-p-tolyl-benzo[1,3]dioxol-5-sulfonyl]-piperidin is,

1-[2,2-bis-(4-chloro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

racemic 1-[2-(4-fluoro-phenyl)-2-phenyl-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

racemic 1-[2-(4-methoxy-phenyl)-2-phenyl-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

racemic 1-[2-(4-chloro-phenyl)-2-p-tolyl-benzo[1,3]dioxol-5-sulfonyl]-4-(4-fluoro-phenyl)-1,2,3,6-tetrahydro-pyridine,

racemic 1-[2-(4-chloro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

racemic 1-[2-(2,4-dichloro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

1-[2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

racemic 1-[2-(3-chloro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

racemic 1-[2-(4-chloro-phenyl)-2-(2-chloro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

racemic (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(3-hydroxy-pyrrolidin-1-yl)-methanon,

4-(2,2-diphenyl-benzo[1,3]dioxol-5-carbonyl)-piperazine-1-carbaldehyde,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-hydroxymethyl-piperidine-1-yl)-methanon,

(1,4-dioxa-8-Aza-Spiro[4.5]Dec-8-yl)-(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-methanon,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanon,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-methyl-piperazine-1-yl)-methanon,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-isopropyl-piperazine-1-yl)-methanon,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-carbonyl)-piperidine--he,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-hydroxy-piperidine-1-yl)-methanon,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-pyrrolidin-1-yl-methanon,

racemic ethyl ester 1-(2,2-diphenyl-benzo[1,3]dioxol-5-carbonyl)-piperidine-3-carboxylic acid,

[4-(5-chloro-2-methoxy-phenyl)-piperazine-1-yl]-(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-methanon,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-m-tolyl-piperazine-1-yl)-methanon,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanon,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-o-tolyl-piperazine-1-yl)-methanon,

racemic ethyl ester 1-(2,2-diphenyl-benzo[1,3]dioxol-5-carbonyl)-piperidine-2-carboxylic acid,

[4-(2,3-dichloro-phenyl)-piperazine-1-yl]-(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-methanon,

[4-(4-chloro-3-trifluoromethyl-phenyl)-piperazine-1-yl]-(2,2-diphenyl-benzo [1,3]dioxol-5-yl)-methanon,

racemic (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(3-hydroxymethyl-piperidine-1-yl)-methanon,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(2,3,5,6-tetrahydro-[1,2']bipyridinyl-4-yl)-methanon,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-pyridin-2-yl-piperazine-1-yl)-methanon,

(4-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-methyl-piperazine-1-yl)-methanon,

(4-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanon,

(4-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanon,

(4,7-dichloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanon,

(4,7-dichlor,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanon,

(4,7-dichloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-methyl-piperazine-1-yl)-methanon,

(7-bromo-4-chloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-methyl-piperazine-1-yl)-methanon,

(7-bromo-4-chloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanon,

(7-bromo-4-chloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanon,

(7-hydroxy-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanon,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-[4-(4-fluoro-phenyl)-3,6-dihydro-2H-pyridine-1-yl]-methanon,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-ylmethyl)-4-(4-fluoro-phenyl)-1,2,3,6-tetrahydro-pyridine

and their pharmaceutically acceptable salts.

Other preferred compounds of General formula (I) are compounds selected from the following groups:

N-(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-benzosulfimide,

N,N-bis(methylsulphonyl)-2,2-diphenyl-1,3-benzodioxol-5-amine,

N,N-bis(butylsulfonyl)-2,2-diphenyl-1,3-benzodioxol-5-amine,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-amide cyclohexanecarbonyl acid,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-amide butane-1-sulfonic acid,

N-(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-butyramide,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-amide morpholine-4-carboxylic acid,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-amide piperidine-1-sulfonic acid,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-amide piperidine-1-carboxylic acid,

[2-(4-chloro-phenyl)-2-(2-fluoro-4-methoxy-dryer is l)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

4-[2-(4-chloro-phenyl)-2-(2-fluoro-4-methoxy-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-morpholine,

[2-(4-methoxy-phenyl)-2-(3-nitro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

4-[2-(4-methoxy-phenyl)-2-(3-nitro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-morpholine,

4-[2-(4-methoxy-phenyl)-5-(morpholine-4-carbonyl)-benzo[1,3]dioxol-2-yl]-benzonitrile,

4-[2-(4-methoxy-phenyl)-5-(morpholine-4-sulfonyl)-benzo[1,3]dioxol-2-yl]-benzonitrile,

[2-(2-fluoro-4-methoxy-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

4-[2-(2-fluoro-4-methoxy-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-morpholine,

(6-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[6-fluoro-2-(4-fluoro-phenyl)-2-phenyl-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2-(2-chloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

(6-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanon,

[6-fluoro-2-(4-fluoro-phenyl)-2-phenyl-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2-(2-chloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

(6-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-[4-(4-fluoro-phenyl)-piperazine-1-yl]-methanon,

[6-fluoro-2-(4-fluoro-phenyl)-2-phenyl-benzo[1,3]dioxol-5-yl]-[4-(4-fluoro-phenyl)-piperazine-1-yl]-methanon,

[2-(2-chloro-phenyl)-6-fluoro-2-(4-methoxy-f the Nile)-benzo[1,3]dioxol-5-yl]-[4-(4-fluoro-phenyl)-piperazine-1-yl]-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-[4-(4-fluoro-phenyl)-piperazine-1-yl]-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

(6-methyl-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanon,

[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

(6-bromo-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanon,

(+)-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

(-)-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2-(2,4-dichloro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2-(2,4-dichloro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

(6-chloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanon,

(6-chloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanon,

ethyl-methyl-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

methyl-propyl-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(2-methyl-pyrrolidin-1-the l-methanon,

azepin-1-alamid 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

azetidin-1-yl-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-methanon,

azepin-1-yl-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-methanon,

(2,2-dimethyl-1-methylcarbamoyl-propyl)-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(2S-methoxymethyl-pyrrolidin-1-yl)-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(2R-hydroxymethyl-pyrrolidin-1-yl)-methanon,

dimethylamide 1-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carbonyl]-pyrrolidin-2R-carboxylic acid,

cyclobutylamine 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

morpholine-4-alamid 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(2,3,5,6-tetrahydro-[1,2']bipyridinyl-4-yl)-methanon,

amide 1-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carbonyl]-pyrrolidin-2S-carboxylic acid,

tert-butoxy-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

cyclopentylamine 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid is,

(tetrahydro-furan-2-ylmethyl)-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-thiomorpholine-4-yl-methanon,

isopropylated 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

pyrrolidin-1-alamid 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

methoxy-methyl-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(3R-hydroxy-pyrrolidin-1-yl)-methanon,

bis-cyclopropylmethyl-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-fluoro-piperidine-1-yl)-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(1,4-dioxa-8-Aza-Spiro[4.5]Dec-8-yl)-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-hydroxymethyl-piperidine-1-yl)-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-hydroxy-4-methyl-piperidine-1-yl)-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-pyrrolidin-1-yl-methanon,

N-{1-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carbonyl]-pyrrolidin-3S-yl}-acetamide", she

cycloheptylamine 2(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

N'-pyridin-2-yl-hydrazide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

(2S-methoxymethyl-pyrrolidin-1-yl)-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(1,1-dioxo-thiomorpholine-4-yl)-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(3-hydroxy-8-Aza-bicyclo[3,2,1]Oct-8-yl)-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(2R-methoxymethyl-pyrrolidin-1-yl)-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(3S-hydroxy-pyrrolidin-1-yl)-methanon,

N-{1-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carbonyl]-pyrrolidin-3R-yl}-acetamide", she

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(2S-hydroxymethyl-pyrrolidin-1-yl)-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-retention,

[2-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

6-(morpholine-4-carbonyl)-2,2-diphenyl-benzo[1,3]dioxol-5-carbonitril,

[2-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-pyrrolidin-1-yl-methanon,

[2,2-bis-(2,4-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methane is h,

[2,2-bis-(2,4-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-pyrrolidin-1-yl-methanon,

[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2,2-bis-(4-bromo-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

4-[2,2-bis-(4-cyano-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carbonyl]-morpholine,

4-[2-(4-bromo-phenyl)-5-fluoro-6-(morpholine-4-carbonyl)-benzo[1,3]dioxol-2-yl]-benzonitrile,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(4-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[6-chloro-2,2-bis-(2,4-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2-(2-chloro-4-fluoro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

4-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-morpholine,

4-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-morpholine,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4,4-debtor-piperidine-1-yl)-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-trifluoromethyl-piperidine-1-yl)-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-yl]-(3S-ethoxy-pyrrolidin-1-yl)-methanon,

(1R-phenyl-ethyl)-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(1-oxo-thiomorpholine-4-yl)-methanon,

[2,2-bis-(2-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[6-fluoro-2,2-bis-(4-trifluoromethyl-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[6-fluoro-2,2-bis-(3-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2-(2-chloro-4-fluoro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(3,4-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2,2-bis-(3,4-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(3-hydroxy-pyrrolidin-1-yl)-methanon,

[2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(4-hydroxy-piperidine-1-yl)-methanon,

ethyl-methyl-amide 2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid,

bis-(2-hydroxy-ethyl)-amide 2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid,

[2,2-bis-(4-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2,2-bis-(4-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-pyrrolidin-1-yl-methanon,

[2,2-bis-(2-chloro-4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2,2-bis-(3,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-2,5-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(2-chloro-4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(2-chloro-4-fluoro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[6-chloro-2,2-bis-(2-chloro-4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

[2,2-bis-(4-bromo-2-fluoro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(3,4-CIS-dihydroxy-pyrrolidin-1-yl)-methanon,

[2,2-bis-(2,3-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[6-fluoro-2,2-bis-(4-triptoreline-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(2-chloro-4,5-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

4-[2,2-bis-(2-chloro-4-fluoro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-morpholine,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(4-fluoro-piperidine-1-yl)-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(4,4-debtor-piperidine-1-yl)-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(4-trifluoromethyl-piperidine-1-yl)-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(4-hydroxy-piperidine-1-yl)-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-thiomorpholine-4-yl-m is the Thanon beach,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-pyrrolidin-1-yl-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(3S-hydroxy-pyrrolidin-1-yl)-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(2S-hydroxymethyl-pyrrolidin-1-yl)-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(2S-methoxymethyl-pyrrolidin-1-yl)-methanon,

(6-chloro-2,2-di-p-tolyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanon,

4-[{6-chloro-10',11'-dihydro-Spiro[1,3-benzodioxole-2,5'-[5H]dibenzo[a,d]cyclohepten]-5-yl}carbonyl]-morpholine,

[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-fluoro-piperidine-1-yl)-methanon,

(4,4-debtor-piperidine-1-yl)-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-methanon,

[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-trifluoromethyl-piperidine-1-yl)-methanon,

[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-thiomorpholine-4-yl-methanon,

(3S-ethoxy-pyrrolidin-1-yl)-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-methanon,

[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-[(S)-(2-methoxymethyl-pyrrolidin-1-yl)]-methanon,

[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-[(S)-2-hydroxymethyl-pyrrolidin-1-yl]-methanon,

[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-[(S)-3-hydroxy-pyrrolidin-1-yl]-methanon,

[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-hydroxy-piperidine-1-yl)-methanon,

4-[2,2-bis(2-chloro-4,5-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-morpholine,

(2,2-di-p-tolyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanon,

(2,2-di-p-tolyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanon,

4-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-morpholine,

4-(6-fluoro-2,2-di-p-tolyl-benzo[1,3]dioxol-5-sulfonyl)-morpholine,

1-{6-fluoro-10',11'-dihydrospiro[1,3-benzodioxole-2,5'-[5H]dibenzo[a,d]cyclohepten]-5-yl}sulfonyl]-piperidine,

4-{6-fluoro-10',11'-dihydrospiro[1,3-benzodioxole-2,5'-[5H]dibenzo[a,d]cyclohepten]-5-yl}sulfonyl]-morpholine,

4-[{10',11'-dihydro-Spiro[1,3-benzodioxole-2,5'-[5H]dibenzo[a,d]cyclohepten]-5-yl}carbonyl]-morpholine,

1-[{10',11'-dihydro-Spiro[1,3-benzodioxole-2,5'-[5H]dibenzo[a,d]cyclohepten]-5-yl}carbonyl]-piperidine,

[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(3-methoxy-piperidine-1-yl)-methanon,

1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-pyrrolidin,

1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

4-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-thiomorpholine,

1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

1-[2,2-bis-(2-chloro-4-fluoro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-pyrrolidin,

1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-4-fluoro-piperidine,

1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-4,4-iftar-piperidine,

1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-4-trifluoromethyl-piperidine,

4-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-thiomorpholine,

1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-2S-methoxymethyl-pyrrolidine,

(2S-methoxymethyl-pyrrolidin-1-yl)-amide 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonic acid,

{1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-pyrrolidin-2S-yl}-methanol,

1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-pyrrolidin-3S-ol,

1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-piperidine-4-ol,

1-[2,2-bis-(2-chloro-4,5-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

4-[{6-fluoro-10',11'-dihydro-Spiro[1,3-benzodioxole-2,5'-[5H]dibenzo[a,d]cyclohepten]-5-yl}-carbonyl]-morpholine,

(6-fluoro-2,2-di-p-tolyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanon,

1-(6-fluoro-2,2-di-p-tolyl-benzo[1,3]dioxol-5-sulfonyl)-piperidine,

[6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-hydroxy-piperidine-1-yl)-methanon,

4-fluoro-1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

4,4-debtor-1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-4-trifluoromethyl-Pipa is one,

1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-2-methoxymethyl-pyrrolidin,

1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-pyrrolidin-3S-ol,

1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine-4-ol,

[2,2-bis-(3-chloro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2,2-bis-(4-cyano-2-fluoro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(3,5-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2,2-bis-(3,5-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

6-fluoro-[2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-[(S)-3-hydroxy-pyrrolidin-1-yl)]-methanon,

ethyl-methyl-amide 6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

(2-methoxy-ethyl)-methyl-amide 6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

[2,2-bis-(3,5-dichloro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2,2-bis-(3,5-dichloro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(3-bromo-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[6-fluoro-2,2-bis-(3-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(3-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2,2-bis-(3-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-metano

and their pharmaceutically acceptable salts.

Particularly preferred compounds of the General formula (I) are compounds selected from the following groups:

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

(+)-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

(-)-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-thiomorpholine-4-yl-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-fluoro-piperidine-1-yl)-methanon,

[2-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-pyrrolidin-1-yl-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4,4-debtor-piperidine-1-yl)-methanon,

[2,2-bis-(4-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2,2-bis-(4-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-pyrrolidin-1-yl-IU the anon

[2,2-bis-(4-bromo-2-fluoro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(4,4-debtor-piperidine-1-yl)-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(4-hydroxy-piperidine-1-yl)-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(3S-hydroxy-pyrrolidin-1-yl)-methanon,

and their pharmaceutically acceptable salts.

The present invention also relates to a method for producing compounds of formula (I)described above. The compounds of formula (I) can be obtained by the methods described below, by the methods provided in the examples or by analogous methods. Suitable reaction conditions for a particular reaction stages are known to the person skilled in the art. Starting materials are either commercially available or can be obtained by methods similar to the methods described below or shown in the examples, or by methods known from the prior art.

The compound of formula (I), where R1-R7and X is defined above, can be obtained using the General methods presented in scheme 1, as described below.

In accordance with scheme 1 from the intermediate compounds catechol of the formula And can be obtained ketal using bis-substituted derivative dichloromethane f is rmula In an inert solvent (for example, toluene or pyridine) or without solvent, in the presence of a base or without it (e.g., pyridine) at elevated temperature (e.g., >100° (C) obtaining product I. Alternatively, the compound of formula (I) can be obtained by the reaction of intermediate compounds catechol of the formula And with the ketone of formula at an elevated temperature (e.g., >150° (C) without solvent or in an inert solvent (e.g. toluene), with removal of water by distillation or by azeotropic distillation or by adding drying agents (for example, molecular sieves or 2,2-dimethoxypropane), by methods known from the prior art (see, for example, .R. Kelly, A. Szabados, Y.-J. Lee, J. Org. Chem. 62 (2) (1997) 428).

Alternatively, the compound of formula (I) can be obtained by the reaction of intermediate compounds catechol of the formula And thioketones formula (C') without solvent or in an inert solvent (e.g. acetonitrile), in the presence of a base or without it (for example, triethylamine), salt of the metal (for example, CuI), by methods known from the prior art (see, for example, I. Shibuya, E. Katoh, Y. Gama, A. Oishi, Y. Taguchi, and T. Tsuchiya, Heterocycles, 43 (1996) 851). The compounds of formula (I), where X represents-CH2-can also be obtained by reduction of the corresponding compounds of formula (I), where X represents-CO-, in a way known from the prior art.

Bis-substituted derivatives of dichloromethane formulas can be easily obtained by methods known from the prior art, from the corresponding ketone by reaction with thionyl chloride in the presence of DMF or other N-formuliruiutsia agent, by reaction with pentachloride phosphorus at elevated temperatures (e.g., >100° (C) in the presence of a suitable solvent or without solvent (for example, chloride oxides of phosphorus), electrophilic aromatic substitution derivative trifloromethyl E with a benzene derivative of formula D in the presence of a Lewis acid (for example, trichloride aluminum) in an inert solvent (for example 1,2-dichloroethane) (for example, R.. Ramchandani, R.D. Wakharkar, A. Sudalai, Tetrahedron Lett. 37 (23) (1996) 4063), the chlorination derived bisaillon (for example, US 5578737 or W. Deuschel, Helv. Chim. Acta 34 (1951) 2403) or, in the case of symmetric bis-substituted derivatives of dichloromethane formulas, electrophilic aromatic substitution of benzene derivative with carbon tetrachloride in the presence of a Lewis acid (for example, AlCl3) in an inert solvent (for example 1,2-dichloroethane) (see, for example, J.P. Picard, C. Kearns, Can. J. Res. 28 (1950) 56).

Category formula And can be easily obtained from the corresponding diphenylmethylsilane ketals of formula (Ia) by treatment with an acid (for example, triperoxonane acid) in fitting the m inert solvent (for example, the methylene chloride or by treatment with an acid (for example, triperoxonane acid) in the presence of a suitable reducing agent (for example, triethylsilane), without solvent or in a suitable inert solvent (e.g. methylene chloride). Alternatively, the catechol of the formula And can be easily obtained from the corresponding bis-benzylamino of catechol of the formula (A') recovery (for example, by hydrogenation in the presence of a suitable catalyst (e.g. palladium on coal)) in the manner known from the prior art. Alternatively, a derivative of catechol of formula F may be condensed with an appropriate amine in a suitable inert solvent (such as DMF, methylene chloride, pyridine or THF) in the presence of a base (e.g. triethylamine). Or the corresponding acid chlorides (X=CO, Z=Cl), or the corresponding sulphonylchloride (X=SO2, Z=Cl), or the corresponding carboxylic acids (X=CO, Z=OH) after activation of a suitable condensing agent (for example, carbonyl diimidazol) are used to receive catecholo formulas And methods known from the prior art. The compounds of formula (A), in which X represents-CH2-can be obtained by reduction of the corresponding compounds of formula (A), in which X represents-CO-, in a way known from the prior art.

The compounds of formula G can be condensed with an appropriate amine in a suitable inert solvent (such as DMF, methylene chloride, pyridine or THF) in the presence of a base (e.g. triethylamine) to produce benzodioxole formula (I). Or the corresponding acid chlorides (X=CO, Z=Cl), or the corresponding sulphonylchloride (X=SO2, Z=Cl), or the corresponding carboxylic acids (X=CO, Z=OH) after activation of a suitable condensing agent (for example, carbonyl diimidazol) are used to receive benzodioxole formula (I) by methods known from the prior art.

Benzodioxole formula (I)in which X represents a single bond, can be obtained in accordance with scheme 5, above, by condensation of an aniline of formula J with the compound of the formula in a suitable inert solvent (such as DMF, methylene chloride, pyridine or THF) in the presence of a base (e.g. triethylamine) to produce benzodioxole formula (Ia). Benzodioxole formula (Ia) can then be condensed with the compound of the formula' in a suitable inert solvent (such as DMF, methylene chloride, pyridine or THF) in the presence of a base (e.g. triethylamine) to produce benzodioxole formula (Ib). Compounds of formulas K and K' can be any suitable the mi chlorides of the acids, or relevant sulphonylchloride, or relevant carbamylcholine, or relevant sulfhemoglobinemia, or the corresponding carboxylic acids R5and R6accordingly, after the activation of an appropriate condensing agent (for example, carbonyl diimidazol).

The invention also relates to compounds of formula (I)described above, obtained in the ways described.

Some compounds of formula (I) may have asymmetric centers and therefore, can exist in more than one stereoisomeric form. The invention thus also relates to compounds, essentially, pure isomeric form relative to one or more asymmetric centers, and mixtures, including racemic mixtures. Such isomers can be obtained by asymmetric synthesis, for example using chiral intermediate compounds, or mixtures can be split into the isomers by conventional methods, for example by chromatography (chromatography with a chiral adsorbent or eluent), or using splitting agents.

It is clear that the compounds of General formula (I) in the present invention can be derivationally functional groups to obtain derivatives that are capable of transforming back to the original compound in vivo.

As described above, the connection fo the formula (I) or their pharmaceutically acceptable salts can be used as medicines for the treatment and/or prevention of diseases, related modulation SW receptors.

Further, the invention also relates to pharmaceutical compositions comprising a compound as defined above, and a pharmaceutically acceptable carrier and/or adjuvant.

Further, the invention relates to compounds as described above for use as therapeutic active substances, particularly as therapeutic active substances for the treatment and/or prevention of diseases associated with the modulation SW receptors.

In another embodiment, the invention relates to a method of treatment and/or prevention of diseases associated with the modulation SW receptors, which includes the introduction of compounds as defined above, a person or an animal.

The invention also relates to the use of compounds as defined above for the treatment and/or prevention of diseases associated with the modulation SW receptors.

In addition, the invention relates to the use of compounds as defined above, to obtain drugs for the treatment and/or prevention of diseases associated with the modulation SW receptors. Such medicines include compound, as defined above.

In this sense, the expression ' diseases associated with the modulation SW receptor"refers to diseases that can be treated and/or predot Amati by modulating SW receptors. Such diseases include, but are not limited to, mental illness, particularly anxiety, and diseases associated with anxiety, psychosis, schizophrenia, depression, drug abuse, including the abuse of psychotropic substances, such as abuse and/or dependence on substances, including alcohol dependence and nicotine dependence, neuropathy, migraine, stress, epilepsy, dyskinesia, Parkinson's disease, amnesia, impaired memory and attention, senile dementia, Alzheimer's disease, eating disorders, obesity, diabetes type II or ainsliezubaida diabetes (NIDD), gastrointestinal diseases, vomiting, diarrhea diseases of the urinary system, cardiovascular disease, infertility, inflammation, infectious diseases, cancer, diseases associated with demyelination, neurospine, in particular atherosclerosis, or syndrome Gillian-Barre, viral encephalitis, cerebral vascular damage and cranial trauma.

In a preferred aspect, the expression ' diseases associated with the modulation SW receptor"refers to nutritional disorders, obesity, diabetes type II or ainsliezubaida diabetes (NIDD), neuronophagia, diarrhea, abuse and/or dependence on substances, including alcohol dependence and nicotine dependence. In a more preferred aspect upon what does the term is associated with eating disorders, obesity, diabetes type II or ainsliezubaida diabetes (NIDD), abuse and/or dependence on substances, including alcohol dependence and nicotine dependence, where obesity is particularly preferred.

As the preferred object is a method of treatment or prevention of diabetes type II (ainsliezubaida diabetes mellitus (NIDDM) in humans, which includes the introduction of therapeutically effective amounts of compounds of formula (I) in combination or mixture with a therapeutically effective amount of a lipase inhibitor, particularly, when the lipase inhibitor is orlistat. It is also an object of the invention is a method as described above for the simultaneous, separate or sequential introduction of the compound of formula (I) and lipase inhibitor, particularly tetrahydrolipstatin.

Another preferred object is a method of treatment or prevention of obesity and diseases associated with obesity, which includes the introduction of therapeutically effective amounts of compounds of formula (I) in combination or mixture with a therapeutically effective amount of other drugs for the treatment of obesity or eating disorders so that together they are an effective profile. Other suitable drugs include, but are not limited to, anorecti the mini-agents the lipase inhibitors and selective inhibitors of the capture of a serotonin (SSRI). Combinations or mixtures of the aforementioned agents may include separate, sequential or simultaneous administration.

A preferred lipase inhibitor is tetrahydrolipstatin.

Fit anorectics agents for use in combination with the compound of the present invention include, but are not limited to, Aminorex, amphora, amphetamine, benzphetamine, chlorphentermine, clobenzorex, klotrix, glominerals, clortermine, cilexetil, dexfenfluramin, dextroamphetamine, diethylpropion, diphemethoxidine, N-ethylamphetamine, fenbutrazate, fenfluramine, penetrex, fenproporex, fluorex, luminares, furfurylmercaptan, levamfetamine, levorotatory, mazindol, mefenorex, metamfepramone, methamphetamine, norpseudoephedrine, phenterex, phendimetrazine, phenmetrazine, phentermine, phenylpropanolamine, pillories and sibutramine and their pharmaceutically acceptable salts.

The most preferred anorectics agents are sibutramine and phentermine.

Suitable selective inhibitors of serotonin uptake for use in combination with the compound of the present invention include: fluoxetine, fluvoxamine, paroxetine and sertraline, and their pharmaceutically acceptable salts.

Illustration of additional biological whom their activities of compounds of the present invention can be demonstrated in in vitro tests, ex vivo and in vivo, which are well known from the prior art. For example, to illustrate the effectiveness of a pharmaceutical agent for the treatment of diseases associated with obesity, such as diabetes, syndrome X, or atherosclerosis and related diseases, such as hypertriglyceridemia and hypercholesteremia can be used in the following tests.

A method of measuring the glucose levels in the blood

In db/db mice (obtained from Jackson Laboratories, Bar Harbor, ME) the blood was collected (through eye or tail vein) and were grouped according to the equivalent average levels of glucose in the blood. They were administered orally (by introduction of a pharmaceutically acceptable carrier) test the connection once a day for 7 to 14 days. Through this time the animals again, the blood was collected through the eye or tail vein and determined the levels of glucose in the blood.

A method of measuring the levels of triglycerides

The hApoAl mice (obtained from Jackson Laboratories, Bar Harbor, ME) the blood was collected (through eye or tail vein) and were grouped according to the equivalent average levels of triglycerides in serum. They were administered orally (by introduction of a pharmaceutically acceptable carrier) test the connection once a day for 7 to 14 days. Then the animals again, the blood was collected through the eye or tail vein and determined the levels trigly is Eridu in serum.

A method of measuring the levels of HDL-cholesterol

To determine the levels of HDL-cholesterol in plasma hApoAl mice the blood was collected and grouped according to the equivalent average levels of HDL-cholesterol in the plasma. Mice was administered orally once daily media or test compound for 7 to 14 days, and then the blood was collected the next day. Plasma was analyzed for content of HDL-cholesterol.

In addition, to illustrate the activities on the Central nervous system of the compounds of the present invention can be used in the following tests in vivo.

Method of test tasks of recognition and spatial memory

Maze Morris Water in the usual way used to assess the tasks of recognition and spatial memory (Jaspers and others, Neurosci. Lett. 117: 149-153, 1990; Morris, J. Neurosci. Methods 11: 47-60, 1984). In this test, animals were placed in the pool, divided into sectors. One platform was hidden in one of the sectors. The animal was placed in the pool and waited for it to find the hidden platform within a predetermined time. During multiple training trials the animal studied the position of the platform and got out of the pool. Animal studied for many indicators in this task. Full length of the passage, the number of tests for detection platform, the waiting time for detection platform and swimming path is registrirovali for each animal. The learning ability of the animal was measured period of time or number of tests required to detect a hidden platform. Lack of memory or improvement was determined by the number of tests or waiting time for detection platform at a certain time delay after detection. Learning and memory can be measured by the number of times that the animal crossed the sector, where was located the platform, during the detection phase.

The way to test drug dependence

Samovodene animal drug is a potential predictor based on connections among people. Modifications of this procedure can also be used to identify compounds that prevent or block the reinforcing properties of drugs, which can cause dependence. Compound that neutralizes Samovodene medicines can prevent the abuse of this drug or dependence on it (Ranaldi and others, Psychopharmacol. 161: 442-448, 2002; Campbell et al., Exp. Clin. Psychopharmacol. 8: 312-25, 2000). In the test Samovodene animals were placed in the operating chamber containing active and inactive lever. Each response on the active lever were injected test compounds or drugs known to Samovodene. N is gatie on the inactive lever had no effect, but also were recorded. Animals were then trained to independently enter the compound/drug during the time when the availability of medicines in each daily session. Lighting camera signals the beginning of the session and the willingness of compounds/drugs. At the end of the session light cameras were off. Originally infusion of drugs occurs with each click of the active lever. As soon as the behavior of the pressing lever set, the number of clicks for works infusion of medicines has increased. After sustained Samovodene compounds/drugs, can be estimated effect of the second connection on the behavior depending on medication. The introduction of this second connection before the session can contribute to, neutralize or not to make any changes to the behavior of Samovodene.

The following tests were carried out to determine the activity of compounds of the formula (I).

The affinity of the compounds of the invention with cannabioids SW receptors was determined using the membrane structures of cells embryos human kidney (SOME), in which cannabioids SW receptor human quickly transfairusa using system virus Semliki Forest combined with [3H]-CP-55,940 as radioligand. After inkubirovanie the freshly prepared composition of cell membranes with [3H]-ligand, with the addition compounds according to the invention or without them, the separation of bound peroxidase and free ligand was carried out by filtration through filters made of glass fiber. The radioactivity on the filter was measured using a scintillation counter for liquids.

The affinity of the compounds of the invention with cannabioids SW receptors was determined using the membrane structures of cells embryos human kidney (SOME), in which cannabioids SW receptor human quickly transfairusa using system virus Semliki Forest combined with [3H]-CP-55,940 as radioligand. After incubation of freshly prepared composition of cell membranes with [3H]-ligand, with the addition compounds according to the invention or without them, the separation of bound peroxidase and free ligand was carried out by filtration through filters made of glass fiber. The radioactivity on the filter was measured using a scintillation counter for liquids.

Cannabioids SW antagonistic activity of the compounds according to the invention was determined by functional studies using Cho cells, in which cannabioids SW receptors man stably expressed (see M. Rinaldi-Carmona and others, J. Pharmacol. Exp. Ther. 278 (1996) 871). Stable expression of cannabioids receptor of human rights in cellular systems was first described in Nature 1990, 346, 561-564 (SW) and Nature 1993, 365, 61-65 (CB2) the COO is responsible. Adenylate cyclase was stimulated by Forskolin and measured the amount of accumulated cyclic AMP. Concomitant activation SW receptor agonists SW receptor (e.g., CP-55,940 or (R)-WIN-55212-2) can decrease caused by Forskolin accumulation of camp depending on the concentration. This response, mediarray SW receptor, can antagonisitic antagonists SW receptor, such as compounds of the present invention.

The compounds of formula (I) show high affinity with SW receptor, certain experimental techniques described Devane and other Mol. Pharmacol. 34 (1988) 605-613. Compounds of the present invention or their pharmaceutically acceptable salts are antagonists are selective for SW receptor with lower affinity IC50=2 μm, preferably from 1 nm to 100 nm. They are at least 10-fold selectivity for the CB2 receptor.

Table 1
Connection exampleIC50[µm]
39<2 μm
46<2 μm
18<2 μm
65<2 μm
4<2 μm
20<2 μm
22<2 μm/td>
75<2 μm
108<2 μm

Connection exampleIC50[MC]
164<2 μm
234<2 μm
271<2 μm

The action of the antagonist/inverse agonist SB receptor caused by CF 55,940 hypothermia in NMRI mice

Animals

This test used the male NMRI mice and obtained from Research Consulting Company Ltd (RCC) Füllinsdorf (Switzerland). This test used mice weighing 30-31, the ambient Temperature was maintained at a level of 20-21°C and a relative humidity of 55-65%. In the rooms provided a 12-hour light cycle in all the trials during the light phase. Access to water and food is free.

Way

All measurements were carried out between 12:00 and 17:00. Mice tolerated in this environment and taught for at least two hours prior to the experiment. They always had free access to food and water. For each dose used 8 mice. Measuring rectal body temperature was recorded using a rectal probe (RET2 Physitemp) and digital thermometer (Digi-sense n°8528-20 Cole Parmer, Chicago USA). The sample was inserted by 3.5 cm in each mouse.

Body temperature was measured sa min before the introduction of the media or the antagonist/inverse agonist SB receptor. After 30 or 90 min intraperitoneal or oral administration of this compound, respectively, were recorded rectal body temperature to assess any impact of the connection. Agonist ST receptor WED 55,940 (0.3 mg/kg) was immediately injected intravenously, then after 20 min after intravenous WED 55,940 again measured body temperature.

The activity of compounds of the formula (I) in vivo was assessed by their ability to regulate food intake by recording food intake in deprived of food animals.

Rats were provided with food for 2 hours a day and were deprived of food for 22 hours When they are accustomed to this schedule, the number of accepted food every day during these 2 h food intake remained constant from day to day.

To test the ability of compounds of the formula (I) to reduce food consumption used 8 animals in cross-examination. Rats were separately placed in Plexiglas chambers with a grid on the floor and put the paper below the floor of the cage to collect all waste. Feeder (becher) was filled with a pre-weighed amount of food for 2 hours At the end of the food intake of the rats were returned to their home cage. Each rat was weighed before the experiment and recorded the amount of food consumed during these 2 h food intake. Various doses of the test compounds or media type and orally 60 minutes before the 2-hour food intake. In the experiment included a positive control Rimonabant (SR141716). Analysis Anova with repeated measures was used with subsequent test Student-Neumann-Keuls.*P<0.05 compared with rats treated with Saline.

In addition, the suitability of the compounds of formula (I) for diseases or disorders may be shown on the disease models in animals, which have been described in the prior art. The following are examples of such disease models in animals: a) reduction of consumption of sweet in monkeys (Behavioural Pharm, 1998, 9,179-181); b) reduction in the consumption of sucrose and ethanol in mice (Psychopharm. 1997, 132, 104-106); C) increased motor activity and room conditions in rats (Psychopharm. 1998, 135, 324-332; Psychopharmacol 2000, 151: 25-30); d) direct locomotor activity in mice (J. Pharm. Exp. Ther. 1996, 277, 586-594); d) reducing opiate Samovodene in mice (Sci. 1999, 283, 401-404).

The compounds of formula (I) and/or their pharmaceutically acceptable salts can be used as medicines, for example, in the form of pharmaceutical compositions for enteral, parenteral or local administration. They can be entered, for example, orally, for example in the form of tablets, coated tablets, dragées, hard and soft gelatine capsules, solutions, emulsions or suspensions, rectally, e.g. in the form of suppositories, parenterally, e.g. in the form of injection solutions or solutions for vivani is, or topically, for example in the form of ointments, creams or oils. Oral introduction is preferred.

Obtaining pharmaceutical compositions can be performed in a manner known to any person skilled in the technical field, introducing the described compounds of formula (I) and/or their pharmaceutically acceptable salts, optionally in combination with other therapeutically valuable substances, herbal forms of introduction together with suitable non-toxic, inert, therapeutically compatible solid or liquid carriers and, if necessary, usual pharmaceutical adjuvants.

Suitable materials for the media are not only inorganic materials, media, and organic materials media. Thus, for example, as materials of the carrier for tablets, coated tablets, dragées and hard gelatin capsules can be used lactose, corn starch or its derivatives, talc, stearic acid or its salts. Suitable materials media for soft gelatine capsules are, for example, vegetable oils, waxes, fats and semi-solid and liquid polyols (depending on the nature of the active ingredient, however, carriers may not apply in the case of soft gelatin capsules). Suitable materials media for the production of solutions and syrups are, is, for example, water, polyols, saccharose, invert sugar and the like. Appropriate media materials for injection solutions are, for example, water, alcohols, polyols, glycerine and vegetable oils. Suitable materials media candles are, for example, natural or hardened oils, waxes, fats and semi-liquid or liquid polyols. Suitable materials media for local trains are glycerides, semi-synthetic and synthetic glycerides, hydrogenated oils, liquid waxes, liquid paraffins, liquid fatty alcohols, sterols, glycols and derivatives of cellulose.

As pharmaceutical adjuvants include conventional stabilizers, preservatives, moisturizing and emulsifiers agents, agents to improve the structure, agents enhance the flavor, salts for modifying the osmotic pressure, buffer substances, soljubilizatory, dyes and masking agents and antioxidants.

The dose of the compounds of formula (I) can vary within wide limits depending on treatable disease, age and individual condition of the patient and the route of administration, and will, of course, depend on the individual requirements in each particular case. For adult patients used a daily dose of from about 1 to 1000 mg, especially from approximately 1 to 100 mg depending on the severity C the disease and the precise pharmacokinetic profile of the compound may be injected into one or more of the daily dosage units, for example at 1 to 3 dosage units.

Pharmaceutical compositions typically contain about 1-500 mg, preferably 1-100 mg of the compounds of formula (I).

The following examples serve to further illustrate the present invention. However, they are not intended to limit the scope of the invention.

Examples

MS = mass spectroscopy, ISP = ion spray (positive ion), tPL= melting point, aq. = water, DMSO = dimethylsulfoxide, NMR = spectroscopy nuclear magnetic resonance, EDCI = hydrochloride N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide, HPLC = high performance liquid chromatography.

Example 1

Obtaining 1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-piperidine

2,2-Diphenyl-benzo[1,3]dioxol-5-sulphonylchloride (3,36 g, 9 mmol) was dissolved in dichloromethane (135 ml). At room temperature was added piperidine (1,33 ml, 13.5 mmol) and ethyldiethanolamine (2.3 ml, 13.5 mmol). The reaction mixture was stirred at room temperature overnight, washed with 1 N aqueous solution of HCl (twice), 1 N aqueous solution of NaOH (twice) and a saturated solution of sodium chloride (once). The organic fraction was dried over sodium sulfate, was filtered. The solvent was evaporated, and the residue was purified column chromatography, using as eluent a mixture (4/1 hexane/e is ylacetic). The selected product is suspended in diethyl ether and the precipitate was filtered, obtaining a white crystalline powder (1.98 g, 52%). tPL: 163-164°C.

Getting 2,2-diphenyl-benzo[1,3]dioxol-5-sulphonylchloride:

Derived sulphonylchloride was obtained according to the methods described in the prior art (WO 9218490, EP 544166).

Method And

Method a is a General method of obtaining 2,2-diphenyl-benzo[1,3]dioxol-5-sulfonamides proceeding from commercially available amines:

2,2-Diphenyl-benzo[1,3]dioxol-5-sulphonylchloride (93 mg, 0.25 mmol) was dissolved in pyridine (1 ml). Was added the appropriate amine (0.25 mmol) and the reaction mixture was heated to 60°With during the night. To the reaction mixture was added water, solid connections and oil separated. The aqueous fraction decantation, the residue was stirred in acetonitrile. The precipitate was filtered off, washed with a small amount of acetonitrile and dried on high vacuum.

The following examples were conducted using the General method is:

Example 2

Obtaining 1-(4-chloro-phenyl)-4-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-piperazine

Using as amine 4-(4-chlorophenyl)piperazine (49.2 mg, 0.25 mmol), specified in the title compound was obtained as a white powder (27 mg, 20%).

MS (ISP): 533,2 (M+N+, 100). NMR (300 MHz, DMSO-d6

Example 3

Obtaining 1-(2,3-dimethyl-phenyl)-4-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-piperazine

Using as amine hydrochloride 4-(2,3-dimetilfenil)piperazine (of 56.7 mg, 0.25 mmol), specified in the title compound was obtained as a white powder (8 mg, 6%).

MS (ISP): 527,2 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,45-of 7.60 (m, 5H), 7,47-of 7.55 (m, 5H), 7,46 (s, 1H), 7,38 (d, 1H), 7,31 (d, 1H), 7,01 (t, 1H), 6.89 in (m, 2H), 3.00 and-of 3.12 (m, 4H), 2,82-is 2.88 (m, 4H), 2,17 (s, 3H), 2,02 (s, 3H).

Example 4

Obtain 1-(2,4-dichloro-phenyl)-4-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-piperazine

Using the amine hydrochloride of 4-(2,4-dichlorophenyl)piperazine (66,9 mg, 0.25 mmol), specified in the title compound was obtained as a yellow powder (32 mg, 23%).

MS (ISP): 567,1 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,45-of 7.60 (m, 10H), 7,42 (s, 1H), 7,34-7,39 (m, 4H), 7,31 (d, 1H), 7,16 (d, 1H), 3.00 and-is 3.08 (m, 8H).

Example 5

Obtaining 1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(4-fluoro-phenyl)-piperazine

Using as amine 4-(4-forefeel)piperazine (45.1 mg, 0.25 mmol), specified in the title compound was obtained as a pale yellow powder (66,4 mg, 51%).

MS (ISP): from 517.2 (M+H+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,51-7,56 (m, 4H), 7,45-7,49 (m, 6N), 7,41 (s, 1H), 737 (d, 1H), 7,29 (d, 1H), 7,02 (t, 1H), 6.90 to-6,94 (m, 1H), 3,11 (m, 4H), 3,01 (m, 4H).

Example 6

Obtaining 1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(3-chloro-phenyl)-piperazine

Using as amine 4-(3-chlorophenyl)piperazine (49.2 mg, 0.25 mmol), specified in the title compound was obtained as a pale yellow powder (91,4 mg, 68%).

MS (ISP): 533,2 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: of 7.48-7,56 (m, 4H), 7,44-of 7.48 (m, 6N), 7,41 (s, 1H), was 7.36 (d, 1H), 7,29 (d, 1H), 7,19 (t, 1H), 6,91 (s, 1H), PC 6.82 (d, 1H), 6,79 (d, 1H), 3,23 (m, 4H), to 3.00 (m, 4H).

Example 7

Getting 4-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-research

Using as amine morpholine (21,8 mg, 0.25 mmol), specified in the title compound was obtained as a white powder (to 51.1 mg, 48%).

MS (ISP): 424,4 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,52-EUR 7.57 (m, 4H), 7,46-7,49 (m, 6N), 7,37 (s, 1H), 7,33 (d, 1H), 7,29 (d, 1H), 3,61 (m, 4H), of 2.86 (m, 4H).

Example 8

Obtaining 1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-phenyl-piperazine

Using as amine 4-phenylpiperazin (40,6 mg, 0.25 mmol), specified in the title compound was obtained as a pale yellow powder (to 78.7 mg, 63%).

MS (ISP): 499,3 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,52-7,56 (m, 4H), 7,44-of 7.48 (m, 6N), 7,41 (s, 1H), 7,35 (d, 1H), 7,30 (d, 1H), 7,19 (t, 2H), 6.89 in (d, 2H), 6,77 (t, 1H), 3,17 (m, 4H), to 3.02 (m, 4H).

Example 9

Obtaining 1-(2,2-diphenylene[1,3]dioxol-5-sulfonyl)-pyrrolidine

Using as the amine pyrrolidine (17,8 mg, 0.25 mmol), specified in the title compound was obtained as a white powder (67,8 mg, 67%).

MS (ISP): 408,3 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,53-EUR 7.57 (m, 4H), 7,43-7,49 (m, 7H), 7,39 (d, 1H), 7,25(d, 1H), 3,12 (m, 4H), of 1.64 (m, 4H).

Example 10

Obtaining 1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(3-methoxy-phenyl)-piperazine

Using as the amine dihydrochloride 4-(3-methoxyphenyl)piperazine (to 66.3 mg, 0.25 mmol), specified in the title compound was obtained as a white powder (75,9 mg, 58%).

MS (ISP): 529,3 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,52-7,56 (m, 4H), 7,44-of 7.48 (m, 6N), 7,41 (s, 1H), 7,37 (d, 1H), 7,29 (d, 1H), was 7.08 (t, 1H), 6.48 in (d, 1H), 6.42 per (s, 1H), 6,38 (d, 1H), 3,68 (s, 3H), 3,17 (m, 4H), 3,01 (m, 4H).

Example 11

Obtaining 1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(4-methoxy-phenyl)-piperazine

Using as the amine dihydrochloride 4-(4-methoxyphenyl)piperazine (to 66.3 mg, 0.25 mmol), specified in the title compound was obtained as a pale brown powder (78,9 mg, 60%).

MS (ISP): 529,2 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,52-EUR 7.57 (m, 4H), 7,45-of 7.48 (m, 6N), 7,38 (s, 1H), was 7.36 (d, 1H), 7,31 (d, 1H), 6,85 (d, 2H), 6,78 (d, 2H), 3,66 (s, 3H), 3,03 (m, 8H).

Example 12

Obtaining 1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(2-methoxy-phenyl)-piperazine

Using as amine 4-(2-methoxyphenyl)piperazine (48,1 mg, 0.25 mmol), specified in the title compound was obtained as a pale yellow powder (to 66.3 mg, 50%).

MS (ISP): 529,2 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,54-7,58 (m, 4H), 7,45-7,49 (m, 6N), 7,41 (s, 1H), 7,38 (d, 1H), 7,31 (d, 1H), 6,85-6,94 (m, 4H), 3,70 (s, 3H), 3,01 (m, 8H).

Example 13

Obtaining 1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(2-chloro-phenyl)-piperazine

Using as amine hydrochloride 4-(2-chlorophenyl)piperazine (58,3 mg, 0.25 mmol), specified in the title compound was obtained as a pale yellow powder (80.4 mg, 60%).

MS (ISP): 533,2 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,54-7,58 (m, 4H), 7,45-7,49 (m, 7H), the 7.43 (s, 1H), 7,38 (d, 1H), 7,32 (d, 1H), 7,30 (t, 1H), 7,15 (d, 1H), 7,06 (t, 1H), 3.04 from (m, 8H).

Example 14

Obtaining 1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(2-fluoro-phenyl)-piperazine

Using as amine 4-(2-fluoro-phenyl)piperazine (45.1 mg, 0.25 mmol), specified in the title compound was obtained as a pale yellow powder (92,8 mg, 72%).

MS (ISP): from 517.2 (M+H+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,54-EUR 7.57 (m, 4H), 7,45-7,49 (m, 6N), 7,42 (s, 1H), 7,37 (d, 1H), 7,31 (d, 1H), of 6.96-7,17 (m, 4H), 3,05 (m, 8H).

Example 15

Getting phenethylamine 2,2-diphenyl-benzo[1,3]dioxol-5-sulfonic acid

Using as amine feilet the Lamin (30,3 mg, 0.25 mmol), specified in the title compound was obtained as a white powder (46,0 mg, 40%).

MS (ISP): 458,4 (M+N+, 100), 475,3 (M+NH4+, 45). NMR (300 MHz, DMSO-d6) ppm: 7,44-7,56 (m, 11H), 7,33-7,21 (m, 2H), 7,10-7,21 (m, 6H), 2.95 and (q, 2H), 2,64 (t, 2H).

Example 16

Getting 1-benzo[1,3]dioxol-5-yl-4-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-piperazine

Using as amine hydrochloride 4-(3,4-dioxymethylene)piperazine (64,7 mg, 0.25 mmol), specified in the title compound was obtained as a brown powder (46.6 mg, 42%).

MS (ISP): 543,2 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,42-7,56 (m, 10H), 7,41 (s, 1H), was 7.36 (d, 1H), 7,29 (d, 1H), 6,74 (d, 1H), 6,63 (s, 1H), 6.30-in (d, 1H), 5,90 (s, 2H), to 3.02 (m, 8H).

Example 17

Getting 4-benzyl-1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-piperidine

Using as amine 4-benzylpiperidine (43,8 mg, 0.25 mmol), specified in the title compound was obtained as a white powder (37.6 mg, 29%).

MS (ISP): 512,3 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,52-7,56 (m, 4H), 7,45-of 7.48 (m, 6N), 7,08-to 7.32 (m, 8H), to 3.58 (m, 2H), 2,45 (m, 2H), 2,19 (m, 2H), 1,58 (m,3H)and 1.15(m, 1H).

Method B

Method B is a General method of obtaining 2,2-diphenyl-benzo[1,3]dioxol-5-sulfonamides proceeding from commercially available amines:

2,2-Diphenyl-benzo[1,3]dioxol-5-sulphonylchloride (93 mg, 0.25 mmol) was dissolved in pyridine (1 ml). EXT is ulali appropriate amine (0.25 mmol), and the reaction mixture was heated to 60°With during the night. To the reaction mixture were added water and solid connections, and the oil separated. The aqueous fraction decantation, the residue was stirred in acetonitrile. The resulting solution was subjected to preparative reverse-phase chromatography (eluent used a mixture of acetonitrile/water containing 0.1% formic acid), the product was isolated by evaporation of eluent and drying.

The following examples were conducted using General method B.

Example 18

Getting 2-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-1,2,3,4-tetrahydro-isoquinoline

Using as amine 1,2,3,4-tetrahydro-isoquinoline (33.3 mg, 0.25 mmol), specified in the title compound was obtained as a yellow powder (35 mg, 30%).

MS (ISP): 470,3 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,40-rate of 7.54 (m, N), from 7.24 (d, 1H), 7,05-7,13 (m, 4 H), 4,19 (s, 2H), 3,30 (t, 2H), 2,82 (m, 2H).

Example 19

Getting benzyl-methylamide 2,2-diphenyl-benzo[1,3]dioxol-5-sulfonic acid

Using as amine N-methylbenzylamine (30,3 mg, 0.25 mmol), specified in the title compound was obtained as a yellow powder (to 48.3 mg, 42%).

MS (ISP): 458,4 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,43-7,58 (m, N), 7,27-7,33 (m, 6H), of 4.13 (s, 2H), 2,53 (s, 3H).

Example 20

Getting benzylamine 2,2-d is phenyl-benzo[1,3]dioxol-5-sulfonic acid

Using as the amine benzylamine (to 26.8 mg, 0.25 mmol), specified in the title compound was obtained as a pale yellow powder (25.1 mg, 22%).

MS (ISN): 442,2 (M-N+, 100), 502,1 (M+SLA-, 20). NMR (300 MHz, DMSO-d6) ppm: 8,06 (Tr, 1H, NH), 7,46-7,56 (m, 11N), was 7.36 (d, 1H), 7,32 (s, 1H), 7,14-to 7.18 (m, 5H), of 3.97 (d, 2H).

Example 21

Obtaining 1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-methyl-[1,4]diazepan

Using as amine N-methylhomopiperazine (28.5 mg, 0.25 mmol), specified in the title compound was obtained as a pale brown powder (23,6 mg, 21%).

MC (ISP): 451,4 (M+H+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,45-7,56 (m, 10H), 7,41 (s, 1H), was 7.36 (d, 1H), 7.23 percent (s, 1H), 3,22-3,39 (m, 4H), of 2.50 (m, 4H, under DMSO peak), of 2.20 (s, 3H), 1,68-of 1.74 (m, 2H).

Example 22

Obtain 1-(3-chloro-5-trifluromethyl-pyridine-2-yl)-4-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-[1,4]diazepan

Using as amine 1-(3-chloro-5-trifluromethyl-pyridine-2-yl)-homopiperazin (69,8 mg, 0.25 mmol), specified in the title compound was obtained as a yellow powder (76,9 mg, 52%).

MS (ISP): 616,1 (M+H+, 100). NMR (300 MHz, DMSO-d6) ppm: scored 8.38 (s, 1H), 7,95 (s, 1H), 7,44-of 7.55 (m, 10H), 7,41 (s, 1H), 7,33 (d, 1H), 7,15 (s, 1H), 3,84 (Tr, 2H), 3,76 (Tr, 2H), 3,44 (Tr, 2H), 3,28 (Tr, 2H), 1,89 (m, 2H).

Example 23

Getting phenylamide 2,2-diphenyl-benzo[1,3]dioxol-5-sulphonic to the slots

Using as amine aniline (23,3 mg, 0.25 mmol), specified in the title compound was obtained as a pale yellow powder (18.2 mg, 17%).

MS (ISN): 428,3 (M-N+, 100). NMR (300 MHz, DMSO-d6) ppm: 10,19 (s, 1H, NH), 7,43-7,52 (m, 10H), 7,32-7,35 (m, 2H), 7,14-7,21 (m, 3H), 6,98-to 7.09 (m, 3H).

Example 24

Obtaining [2-(4-methoxy-phenyl)-ethyl]-amide 2,2-diphenyl-benzo[1,3]dioxol-5-sulfonate acid

Using as amine 2-(4-methoxyphenyl)ethylamine (of 37.8 mg, 0.25 mmol), specified in the title compound was obtained as a pale yellow powder (67,1 mg, 55%).

MS (ISN): 486,2 (M-N+, 100), 546,1 (M+SLA-, 35). NMR (300 MHz, DMSO-d6) ppm: 7,44-7,58 (m, 11N), 7,34-7,37 (m, 2H), 7,19 (d, 1H), 7,03 (d, 2H), 6,79 (d, 2H), 3,69 (s, 3H), 2,89 (kV, 2H), 2,58 (t, 2H).

Example 25

Obtaining 1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-methyl-piperazine

Using as amine N-methylpiperazine (25.0 mg, 0.25 mmol), specified in the title compound was obtained as a white powder (11 mg, 10%).

MS (ISP): 437,4 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,53-EUR 7.57 (m, 4H), 7,45-7,49 (m, 6N), was 7.36 (s, 1H), 7,32 (d, 1H), 7,29 (d, 1H), 2,87 (m, 4H), 2,33 (m, 4H), 2,11 (s, 3H).

Example 26

Obtaining 1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(4-fluoro-phenyl)-1,2,3,6-tetrahydro-pyridine

The hydrochloride of 4-(4-forefeel)-1,2,3,-tetrahydropyridine (2,56 g, 12 mmol) suspended in dichloromethane (150 ml). Added ethyldiethanolamine (4,2 ml, 25 mmol)and the solution was stirred at room temperature for 10 minutes was Added 2,2-diphenyl-benzo[1,3]dioxol-5-sulphonylchloride (and 3.72 g, 10 mmol), the reaction mixture was stirred at room temperature for 2 hours the Solvent was evaporated, and the residue was purified column chromatography on silica gel (100 g, eluent-dichloromethane). The obtained product was stirred in n-hexane, filtered and dried, obtaining the sulfonamide in the form of white crystals (3,86 g, 75%).

MS (ISP): 514,3 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,50-rate of 7.54 (m, 4H), 7,44-of 7.48 (m, 7H), was 7.36-7,40 (m, 3H), 7,26 (d, 1H), to 7.09 (t, 2H), 6,03 (m, 1H), 3,68 (m, 2H), 3,23 (t, 2H), 2,50 (s, 2H, under DMSO peak).

Example 27

Getting 4-(4-chloro-phenyl)-1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-1,2,3,6-tetrahydropyridine

The hydrochloride of 4-(4-chlorophenyl)-1,2,3,4-tetrahydropyridine (19,37 mg, 0.10 mmol) suspended in dichloromethane (2 ml). Added ethyldiethanolamine (or 0.035 ml, 0.20 mmol)and the solution was shaken for 10 min at room temperature. Added 2,2-diphenyl-benzo[1,3]dioxol-5-sulphonylchloride (37,28 mg, 0.10 mmol)and the reaction mixture was shaken at room temperature for 12 hours was Added an aqueous solution of HCl (0.1 N., 1.0 ml)and the mixture was shaken for 30 min, removed water fraction and organic the positive fraction was concentrated and was purified by the method of preparative reversed-phase HPLC (YMC, ODS-AQ filling; 20%→95% CH3CN/H2O)receiving the target sulfonamide (2.6 mg, 5%).

MS (ISP): 530,2 (M+N+, 100). NMR (500 MHz, DMSO-d6) ppm: 7,31-7,56 (m, N), 7,26 (d, 1H), 6,10 (m, 1H), 3,70 (m, 2H), 3,24 (m, 2H), 2,50 (m, 2H, under DMSO peak).

Example 28

Obtaining 1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-phenyl-1,2,3,6-tetrahydro-pyridine

Hydrochloride 4-phenyl-1,2,3,4-tetrahydropyridine (15,92 mg, 0.10 mmol) suspended in dichloromethane (2 ml). Added ethyldiethanolamine (or 0.035 ml, 0.20 mmol)and the solution was shaken for 10 min at room temperature. Added 2,2-diphenyl-benzo[1,3]dioxol-5-sulphonylchloride (37,28 mg, 0.10 mmol)and the reaction mixture was shaken for 12 h at room temperature. Was added an aqueous solution of HCl (0.1 N., 1.0 ml). and the mixture was shaken for 30 min, the aqueous fraction was removed, and the organic fraction was concentrated and was purified by the method of preparative reversed-phase HPLC (YMC, ODS-AQ filling; 20%→95% SN3CN/H2O)receiving the target sulfonamide (23,6 mg, 48%).

MS (ISP): 596,2 (M+N+, 100). NMR (500 MHz, DMSO-d6) ppm: 7,22-of 7.55 (m, 17H), the 6.06 (m, 1H), 3,70 (m, 2H), 3,24 (m, 2H), 2,50 (m, 2H, under DMSO peak).

Example 29

Obtaining racemic 1-[2-(2-chloro-phenyl)-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine

Method In

A solution of 4-(piperidine-1-sulfonyl)-benzo is -1,2-diol (60 mg, 0.2 mmol) and (4-methoxyphenyl)-(2-chlorophenyl)-dichloromethane (51 mg, 0.2 mmol) in toluene (2 ml) was boiled under reflux overnight. After cooling the reaction mixture to room temperature, the solvent was evaporated. The residue was dissolved in dichloromethane and was purified column chromatography on silica gel (dichloromethane as eluent). The product was obtained as a colourless powder (42 mg, 39%).

MS (ISP): 486,3 (M+N+, 100). NMR (300 MHz, CDCl3) ppm: 7,80-of 7.90 (m, 1H), 7,30-the 7.43 (m, 8H), 6,97 (d, 1H), 6.89 in (d, 1H), 3,82 (s, 3H), 2,98 (m, 4H), 1,60-1,70 (m, 4H), of 1.40-1.50 (m, 2H).

The following examples was performed according to General method:

Example 30

Obtaining racemic 1-[2-(2-chloro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine

Using as starting compound 4-forefeel-2-chlorophenyl-dichloromethane (57 mg, 0.2 mmol), specified in the title compound was obtained as a colourless foam (68 mg, 71%). Column chromatography was performed on silica gel (25 g, as eluent used dichloromethane).

MS (ISP): 474,2 (M+N+, 100). NMR (300 MHz, CDCl3) ppm: to 7.84 (m, 1H), 7,32-7,47 (m, 6N), 7,27 (d, 1H), was 7.08 (t, 2H), 6,99 (d, 1H), 2.95 and-a 3.01 (m, 4H), 1,60 by 1.68 (m, 4H), of 1.42 to 1.47 (m, 2H).

Example 31

Obtaining racemic 1-[2-(2-chloro-phenyl)-2-p-tolyl-benzo[1,3]dioxol-5-sulfonyl]-piperidine

Using as a source is about connections 4-were-2-chlorophenyl-dichloromethane (57 mg, 0.2 mmol)specified in the title compound was obtained as a pale yellow foam (46 mg, 44%). Column chromatography was performed on silica gel (25 g, as eluent used dichloromethane).

MS (ISP): 470,2 (M+N+, 100). NMR (300 MHz, CDCl3) ppm: 7,83 (m, 1H), 7,31-7,42 (m, 7H), 7,20 (d, 2H), 6,97 (d, 1H), 2,96-to 3.02 (m, 4H), 1,60 by 1.68 (m, 4H), 1,42 of 1.46 (m, 2H).

Example 32

Obtaining racemic 1-[2-(4-chloro-phenyl)-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine

Using as starting compound 4-methoxyphenyl-4-chlorophenyl-dichloromethane (60 mg, 0.2 mmol), specified in the title compound was obtained as a pale red powder (35 mg, 36%). Column chromatography was performed on silica gel (25 g, as eluent used dichloromethane).

MS (EI): 485,2 (M+, 65), 374,2 ([M-PhCl]+, 100). NMR (300 MHz, CDCl3) ppm 7,49 (d, 2H), 7,42 (d, 2H), 7,32 (d, 2H), 7,22 (s, 1H), 6,94 (d, 1H), 6.90 to (d, 2H), 2.95 and-2,99 (m, 4H), 1,60 by 1.68 (m, 4H), 1,40-of 1.44 (m, 2H).

Example 33

Obtaining racemic 1-[2-(4-chloro-phenyl)-2-p-tolyl-benzo[1,3]dioxol-5-sulfonyl]-piperidine

Using as starting compound 4-were-4-chlorophenyl-dichloromethane (85 mg, 0.3 mmol), specified in the title compound was obtained as a colourless foam (138 mg, 97%). Column chromatography was performed on silica gel (25 g, as eluent which the objects of study were a mixture 4/1 hexane/ethyl acetate).

MS (ISP): 470,2 (M+, 100). NMR (300 MHz, CDCl3) ppm: 7,49 (d, 2H), 7,40 (d, 2H), was 7.36 (d, 2H), 7,31 (d, 1H), 7.23 percent (d, 1H), 6,94 (d, 2H), 2.95 and-2,99 (m, 4H), 1,60 by 1.68 (m, 4H), 1,39 of 1.46 (m, 2H).

Example 34

Obtaining 1-[2,2-bis-(4-chloro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine

Using as starting compound bis-(4-chlorophenyl)-dichloromethane (61 mg, 0.2 mmol), specified in the title compound was obtained as a colourless powder (77 mg, 78%). Column chromatography was performed on silica gel (25 g, as eluent used dichloromethane).

MS (EI): 489,1 (M+, 30), 378,1 ([M-PhCl]+, 30), 231,1 (70), 84,3 (100). NMR (300 MHz, CDCl3) ppm: 7,47 (d, 4H), 7,37 (d, 4H), 7,33 (d, 1H), 7,25 (s, 1H), of 6.96 (d, 1H), 2.95 and 3.00 for (m, 4H), 1,60 by 1.68 (m, 4H), 1,40-of 1.46 (m, 2H).

Example 35

Obtaining racemic 1-[2-(4-fluoro-phenyl)-2-phenyl-benzo[1,3]dioxol-5-sulfonyl]-piperidine

Using as starting compound 4-forefeel-phenyl-dichloromethane (51 mg, 0.2 mmol), specified in the title compound was obtained after stirring the crude product in diethyl ether, filtration and drying in the form of white crystalline powder (66 mg, 75%). tPL: 125-126°C.

Example 36

Obtaining racemic 1-[2-(4-methoxy-phenyl)-2-phenyl-benzo[1,3]dioxol-5-sulfonyl]-piperidine

Using as starting compounds is of 4-methoxyphenyl-phenyl-dichloromethane (53 mg, 0.2 mmol)specified in the title compound was obtained as a white powder (56 mg, 62%). Column chromatography was performed on silica gel (25 g, as eluent used a mixture 4/1 hexane/ethyl acetate).

MS (ISP): 452,4 (M+, 100). NMR (300 MHz, CDCl3) ppm: 7,41-rate of 7.54 (m, 7H), 7,33 (s, 1H), 7,31 (d, 4H), of 7.23 (d, 1H), 7,00 (d, 2H), 3,76 (s, 3H), 2,87 (m, 4H), of 1.53 (m, 4H), of 1.35 (m, 2H).

Example 37

Obtaining racemic 1-[2-(4-chloro-phenyl)-2-p-tolyl-benzo[1,3]dioxol-5-sulfonyl]-4-(4-fluoro-phenyl)-1,2,3,6-tetrahydro-pyridine

Using as starting compounds 4-chlorophenyl-4-were-dichloromethane (57 mg, 0.2 mmol) and 4-[4-(4-fluoro-phenyl)-3,6-dihydro-2H-pyridine-1-sulfonyl]-benzene-1,2-diol (69 mg, 0.2 mmol), after placing the residue in a mixture of hexane/ethyl acetate (4/1), stirring for 10 minutes, filtering the precipitate and drying specified in the title compound was obtained as a colorless crystalline powder (90 mg, 80%).

MS (EI): 561,2 (M+, 10), 176,2 (100), 149,2 (50). NMR (300 MHz, CDCl3) ppm: 7,47 (d, 2H), 7.18 in-7,40 (m, 9H), of 6.99 (d, 2H), of 6.96 (d, 2H), of 5.89 (m, 1H, in), 3.75 (m, 2H), 3,32 (t, 2H), 2.57 m (m, 2H), a 2.36 (s, 3H).

Getting 4-[4-(4-fluoro-phenyl)-3,6-dihydro-2H-pyridine-1-sulfonyl]-benzene-1,2-diol.

1-(2,2-Diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(4-fluoro-phenyl)-1,2,3,6-tetrahydro-pyridine (3.2 g, 6.2 mmol) was dissolved in dichloromethane (100 ml). Was added dropwise triperoxonane acid (50 ml), and reacts the district and the mixture was stirred for 5 h at room temperature. The solvent was evaporated, and the residue was purified column chromatography on silica gel (100 g, as eluent used first dichloromethane, then ethyl acetate). After crystallization from a mixture of diethyl ether/hexane, the product was obtained as a white powder (2.1 g, 96%).

MS (ISN): 348,2 (M-N+, 100). NMR (300 MHz, DMSO-d6) ppm rating: 10.0 (br s, 1H, HE), 9,80 (br s, 1H, HE), 7,44 (d, 1H), 7,42 (d, 1H), 7,08-7,19 (m, 4H), 6,92 (d, 1H), 6,07 (br s, 1H)and 3.59 (br s, 2H), 3,13 (m, 2H), of 2.51 (m, 2H, under DMSO peak).

Example 38

Obtaining racemic 1-[2-(4-chloro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine

Using as starting compound 4-chlorophenyl-4-forefeel-dichloromethane (57 mg, 0.2 mmol), specified in the title compound was obtained as a colourless foam (77 mg, 81%). Column chromatography was performed on silica gel (25 g, eluent 4/1 hexane/ethyl acetate).

MS (EI): 473,2 (M+, 30), 215,2 (40), 84,3 (100). NMR (300 MHz, CDCl3) ppm: 7,46-7,53 (m, 4H), 7,32-7,39 (m, 3H), 7,24 (s, 1H), to 7.09 (t, 2H), of 6.96 (d, 1H), 2,96-3,00 (m, 4H), 1,60 by 1.68 (m, 4H), 1,40-of 1.46 (m, 2H).

Example 39

Obtaining racemic 1-[2-(2,4-dichloro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine

Using as starting compound 2,4-dichlorophenyl-4-forefeel-dichloromethane (65 mg, 0.2 mmol), specified in the title compound was obtained as colorless foams is (81 mg, 80%). Column chromatography was performed on silica gel (25 g, eluent 4/1 hexane/ethyl acetate).

MS (ISP): 508,2 (M+N+, 100). NMR (300 MHz, CDCl3) ppm: for 7.78 (d, 1H), 7,32-7,47 (m, 3H), 7,32-7,37 (m, 2H), 7,28 (s, 1H), was 7.08 (t, 2H), 6,99 (d, 1H), 2,97-3,00 (m, 4H), 1,61 by 1.68 (m, 4H), of 1.40 to 1.47 (m, 2H).

Example 40

Obtaining 1-[2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine

Using as starting compound bis-(4-forefeel)-dichloromethane (55 mg, 0.2 mmol), specified in the title compound was obtained as a colourless foam (75 mg, 82%). Column chromatography was performed on silica gel (25 g, eluent 4/1 hexane/ethyl acetate). tPL: 148-149°C.

Example 41

Obtaining racemic 1-[2-(3-chloro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine

Using as starting compound 3-chlorophenyl-4-forefeel-dichloromethane (58 mg, 0.2 mmol), specified in the title compound was obtained as a colourless viscous oil (82 mg, 86%). Column chromatography was performed on silica gel (25 g, eluent 4/1 hexane/ethyl acetate).

MS (ISP): 474,2 (M+N+, 100). NMR (300 MHz, CDCl3) ppm: 7,49-of 7.55 (m, 3H), 7,33-7,44 (m, 4H), 7,26 (s, 1H), to 7.09 (t, 2H), 6,97 (d, 1H), 2,96-3,00 (m, 4H), 1,60 by 1.68 (m, 4H), 1,40-of 1.46 (m, 2H).

Example 42

Obtaining racemic 1-[2-(4-chloro-phenyl)-2-(2-chloro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine

Using as starting compound 2-chlorophenyl-4-chlorophenyl-dichloromethane (61 mg, 0.2 mmol), specified in the title compound was obtained as a colourless powder (40 mg, 41%). Column chromatography was performed on silica gel (25 g, eluent dichloromethane).

MS (EI): 489,1 (M+, 30), 378,1 (35), 231,1 (60), 84,2 (100). NMR (300 MHz, CDCl3) ppm: 7,42-7,86 (m, 1H), 7,33-7,44 (m, 8H), 7,27 (d, 1H), 6,99 (d, 1H), 2,96-3,00 (m, 4H), 1,60 by 1.68 (m, 4H), of 1.42 to 1.47 (m, 2H).

Method G

Derivatives of bis-aryl-dichloromethane necessary for obtaining the above-described compounds were obtained according to the method of G, according to the methodology described in the prior art (R.. Ramchandani, R.D. Wakharkar, A. Sudalai, Tetrahedron Lett. 37 (23) (1996) 4063-4064).

Receive (4-methoxyphenyl)(2-chlorophenyl)-dichloromethane:

Trichloride aluminum (400 mg, 3 mmol) suspended in 1,2-dichloroethane (1.4 ml). At a temperature of 0°C in an atmosphere of argon was added 2-chlorobenzotrifluoride (180 mg, 1 mmol). To the resulting deep red solution was added anisole (108 mg, 1 mmol). The reaction mixture was stirred at a temperature of 0°C for 3 hours, the Reaction mixture was poured over ice, stirred for 5 min and twice was extracted with dichloromethane. The organic fractions were combined, washed with a saturated solution of sodium chloride, dried over sodium sulfate and was filtered. The solvent was evaporated, getting the product in the form of dark red Vaskov the oil (416 mg 138%), which without further purification was used in the subsequent stages of the synthesis.

Known bis-aryl-dichlormethane obtained by this method is:

4-Were-4-chlorophenyl-dichloromethane

Bis-(4-chlorophenyl)-dichloromethane

2-Chlorophenyl-4-chlorophenyl-dichloromethane

(4-Methoxyphenyl)(2-chlorophenyl)-dichloromethane

The following derivatives of bis-aryl-dichloromethane, not previously described in the prior art, obtained by the method of G, proceeding from commercially available starting compounds. Connections are not cleared, because some of them unstable when column chromatography, and used as crude products without purification in the subsequent stages of the synthesis.

Getting 4-forefeel-2-chlorophenyl-dichloromethane:

2-chlorobenzotrifluoride (180 mg, 1 mmol), AlCl3(400 mg, 3 mmol) and vorobtsova (96 mg, 1 mmol), light yellow oil (380 mg, 131% crude).

Getting 4-were-2-chlorophenyl-dichloromethane:

2-chlorobenzotrifluoride (180 mg, 1 mmol), AlCl3(400 mg, 3 mmol) and toluene (92 mg, 1 mmol), light yellow oil (345 mg, 120% crude).

Getting 4-methoxyphenyl-4-chlorophenyl-dichloromethane:

4-chlorobenzotrifluoride (180 mg, 1 mmol), AlCl3(400 mg, 3 mmol) and anisole (108 mg, 1 mmol), red powder (345 mg, 120% crude), contains benzophenone (approx. 30%).

Getting 4-chlorophenyl-4-forefeel-dichloromethane:

4-chlorobenzotrifluoride (180 mg, 1 mm is l), AlCl3(400 mg, 3 mmol) and vorobtsova (96 mg, 1 mmol), light yellow oil (382 mg, 131% crude).

Obtaining 2,4-dichlorophenyl-4-forefeel-dichloromethane:

From 2,4-dichlorobenzotrifluoride (215 mg, 1 mmol), AlCl3(400 mg, 3 mmol) and vorobtsova (96 mg, 1 mmol), light yellow oil (382 mg, 118% crude).

Obtaining 3-chlorophenyl-4-forefeel-dichloromethane:

3-chlorobenzotrifluoride (180 mg, 1 mmol), AlCl3(400 mg, 3 mmol) and vorobtsova (96 mg, 1 mmol), light yellow oil (384 mg, 132% crude).

Getting 4-forefeel-phenyl-dichloromethane:

From benzotrifluoride (146 mg, 1 mmol), AlCl3(400 mg, 3 mmol) and vorobtsova (96 mg, 1 mmol), light yellow oil (335 mg, 131% crude).

The following bis-aryl-dichlormethane known from the prior art, but their synthesis is not described. These compounds were obtained according to method G:

Obtaining bis-(4-forefeel)-dichloromethane (EP 96008).

4-forobulgaria (164 mg, 1 mmol), AlCl3(400 mg, 3 mmol) and vorobtsova (96 mg, 1 mmol), light yellow oil (377 mg, 138% crude).

Getting 4-methoxyphenyl-phenyl-dichloromethane (R. Laatikainen, V. Kral, J. Chem. Soc., Perkin Trans. 2 (8) (1985) 1091-1100; US 3824310):

From benzotrifluoride (146 mg, 1 mmol), AlCl3(400 mg, 3 mmol) and anisole (108 mg, 1 mmol), dark red viscous oil (352 mg, 132% crude).

Getting 4-(piperidine-1-sulfonyl)-benzene-1,2-diol:

1-(2,2-Diphenyl-benzo[1,3]dioxol-5-sulfonyl)-piperidine (1.92 g, 4,mmol) was dissolved in dichloromethane (69 ml). At room temperature was added triperoxonane acid (20.7 ml) and water (8 drops). The reaction mixture was stirred at room temperature for 24 h the solvent was Evaporated, the residue was transferred into n-pentane and evaporated to remove triperoxonane acid (the procedure was repeated three times). The residue was purified column chromatography on silica gel (100 g, was suirable dichloromethane, then with a mixture 1/19 methanol/dichloromethane). The product was besieged from a mixture of diethyl ether/n-pentane. The solvent was evaporated, and the residue was stirred with n-pentane. The precipitate was filtered and dried, obtaining the product as a white crystalline powder (1.13 g, 97%).

MS (ISN): 256,0 (M-N+, 100). NMR (300 MHz, DMSO-d6) ppm: 9,98(s, 1H, HE), RS 9.69 (s, 1H, HE), 7,05 (DD, 1H), 7,01 (DD, 1H), 6.90 to (d, 1H), 2,78-and 2.83 (m, 4H), 1.50 is by 1.68 (m, 4H), 1,30-1,40 (m, 2H).

Method D

Benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (87 mg, 0.2 mmol), corresponding amine (22 mg, 0.25 mmol) and ethyldiethanolamine (32 mg, 0.25 mmol) was dissolved in acetonitrile (2 ml) and stirred at room temperature for 3 hours was Added water (20 ml)and the reaction mixture was stirred at room temperature for 1 h the Precipitate was filtered, washed with water and dried on high vacuum, getting the product in the form of white crystalline powder.

Obtaining an activated ester, benzor the azole-1-silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid, described in the prior art (EP 544166).

The following examples were conducted according to method D:

Example 43

Obtaining racemic (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(3-hydroxy-pyrrolidin-1-yl)-methanone

From benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (87 mg, 0.2 mmol) and 3-pyrrolidinone (22 mg, 0.25 mmol), specified in the title compound was obtained as a white crystalline powder (73 mg, 94%). tPL: 106-107°C.

Example 44

Getting 4-(2,2-diphenyl-benzo[1,3]dioxol-5-carbonyl)-piperazine-1-carbaldehyde

From benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (87 mg, 0.2 mmol) and formyl-piperazine (32 mg, 90% purity, 0.25 mmol) specified in the title compound was obtained as a white crystalline powder (73 mg, 88%). tPL176-177°C.

Example 45

Receiving (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-hydroxymethyl-piperidine-1-yl)-methanone

From benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (87 mg, 0.2 mmol) and 4-(hydroxymethyl)-piperidine (29 mg, 0.25 mmol) specified in the title compound was obtained as a white crystalline powder (76 mg, 91%). tPL197-198°C.

Example 46

Receiving (1,4-dioxa-8-Aza-Spiro[4.5]the EC-8-yl)-(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-methanone

From benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (87 mg, 0.2 mmol) and 1,4-dioxa-8 azaspiro(4,5)decane (36 mg, 0.25 mmol) specified in the title compound was obtained as a white crystalline powder (74 mg, 83%). tPL150-151°C.

Example 47

Receiving (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanone

From benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (87 mg, 0.2 mmol) and research (22 mg, 0.25 mmol) specified in the title compound was obtained as a white crystalline powder (64 mg, 82%). tPL149-150°C.

Example 48

Receiving (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-methyl-piperazine-1-yl)-methanone

From benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (87 mg, 0.2 mmol) and 1-methylpiperazine (25 mg, 0.25 mmol) specified in the title compound was obtained as a white crystalline powder (72 mg, 90%). tPL115-116°C.

Example 49

Receiving (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-isopropyl-piperazine-1-yl)-methanone

From benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (87 mg, 0.2 mmol) and 1-(2-propyl)-piperazine (32 mg, 0.25 mmol) specified in C is the cylinder compound was obtained as a colourless foam (84 mg, 98%). Processing reaction: after adding water (20 ml) the reaction mixture was stirred for 1 h at room temperature. Added dichloromethane, and the mixture was stirred for 10 min. the Organic fraction was separated, washed with water, saturated sodium chloride solution and dried over sodium sulfate. After evaporation of the solvent the product was dried in high vacuum.

MS (ISP): 429,6 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,51-7,56 (m, 4H), 7,43-7,47 (m, 6N), was 7.08 (d, 1H), 7,07 (s, 1H), 6,92 (d, 1H), 3,3-3,6 (br m, 4H), 2,65 (Sept, 1H), 2,38-to 2.42 (br m, 4H), of 0.95 (d, 6N).

Example 50

Obtaining 1-(2,2-diphenyl-benzo[1,3]dioxol-5-carbonyl)-piperidine-4-it

From benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (87 mg, 0.2 mmol), monohydrate hydrochloride 4-piperidone (39 mg, 0.25 mmol) and ethyldiethanolamine (58 mg, 0.45 mmol) specified in the title compound was obtained as a pale yellow foam (75 mg, 94%). Processing reaction: after adding water (20 ml) the reaction mixture was stirred for 1 h at room temperature. Added dichloromethane, and the mixture was stirred for 10 min. the Organic fraction was separated, washed with water and dried over sodium sulfate. After evaporation of the solvent the product was dried in high vacuum.

MS (ISP): 400,5 (M+N+, 100), 417,3 (M+NH4+, 40), 799,3 (2M+the +, 20). NMR (300 MHz, DMSO-d6) ppm: 7,47-EUR 7.57 (m, 4H), 7,44-7,47 (m, 6H), 7,17 (s, 1H), 7,11 (d, 1H), 7,05 (d, 1H), 3,62-is 3.82 (br m, 4H), 2,39 is 2.44 (br m, 4H).

Example 51

Receiving (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-hydroxy-piperidine-1-yl)-methanone

From benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (87 mg, 0.2 mmol), hydrochloride 4-hydroxypiperidine (34 mg, 0.25 mmol) and ethyldiethanolamine (58 mg, 0.45 mmol) specified in the title compound was obtained as a colourless foam (73 mg, 91%). Processing reaction: after adding water (20 ml) the reaction mixture was stirred for 1 h at room temperature. Added dichloromethane, and the mixture was stirred for 10 min. the Organic fraction was separated, washed with water and dried over sodium sulfate. After evaporation of the solvent the product was dried in high vacuum.

MS (ISP): 402,5 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,51-7,56 (m, 4H), 7,43-7,49 (m, 6H), 7,07 (d, 1H), 7,05 (s, 1H), 6,91 (d, 1H), amounts to 4.76 (d, 1H, HE), 3,70 (m, 1H), 3,11-3,18 (m, 2H), of 2.51 (m, 2H, under DMSO peak), 1,63-to 1.79 (m, 2H), 1,25-of 1.39 (m, 2H).

Example 52

Receiving (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-pyrrolidin-1-yl-methanone

From benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (87 mg, 0.2 mmol), pyrrolidine (18 mg, 0.25 mmol) and ethyldiethanolamine (32 mg, 0.25 mmol) specified in the head of the compound was obtained as a pale yellow foam (75 mg, 91%). Processing reaction: after adding water (20 ml) the reaction mixture was stirred for 1 h at room temperature. Added dichloromethane, and the mixture was stirred for 10 min. the Organic fraction was separated, washed with water and dried over sodium sulfate. After evaporation of the solvent the product was dried in high vacuum.

MS (ISP): 372,3 (M+N+, 100), 743,3 (2M+H+, 80). NMR (300 MHz, DMSO-d6) ppm: of 7.48-7,56 (m, 4H), 7,43-of 7.48 (m, 6H), 7,18 (s, 1H), to 7.09 (d, 1H), 7,05 (d, 1H), 3,35-of 3.42 (m, 4H), 1.77 in-of 1.84 (m, 4H).

Example 53

Obtaining racemic ethyl ester 1-(2,2-diphenyl-benzo[1,3]dioxol-5-carbonyl)-piperidine-3-carboxylic acid

Method E

Benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (87 mg, 0.2 mmol), racemic Eternitate (36 mg, 0.25 mmol) and ethyldiethanolamine (32 mg, 0.25 mmol) was dissolved in acetonitrile (1 ml) and stirred at room temperature overnight. The reaction mixture was purified by the method of preparative HPLC (eluent acetonitrile/water with 0.1% formic acid as gradient)to give the product as a white powder (24,8 mg, 27%).

MS (ISP): 458,4 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,52-7,56 (m, 4H), 7,43-7,46 (m, 6N), was 7.08 (d, 1H), 7,07 (s, 1H), 6,92 (d, 1H), a 4.03 (m, 2H), 3,12 (m, 2H), 2,50 (m, 2H, under DMSO peak), with 1.92 (m, 1H), and 1.63 (m, 2H), USD 1.43 (m, 2H), 1,12 (m, 3H).

The following examples were performed according to described the WMD above method E:

Example 54

Obtain [4-(5-chloro-2-methoxy-phenyl)-piperazine-1-yl]-(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-methanone

From benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (87 mg, 0.2 mmol), hydrochloride of 1-(5-chloro-2-methoxy-phenyl)piperazine (66 mg, 0.25 mmol) and ethyldiethanolamine (64 mg, 0.50 mmol) specified in the title compound was obtained as a white powder (42.7 mg, 41%).

MS (ISP): 527,1 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,44-of 7.60 (m, 10H), 6.87 in-7,01 (m, 6N), of 3.78 (s, 3H), 3,06 (br m, 4H), 2,97 (br m, 4H).

Example 55

Receiving (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-m-tolyl-piperazine-1-yl)-methanone

From benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (87 mg, 0.2 mmol), hydrochloride of 1-(3-tolyl)piperazine (62 mg, 0.25 mmol) and ethyldiethanolamine (96 mg, 0.75 mmol) specified in the title compound was obtained as a pale yellow powder (14,0 mg, 15%).

MS (ISP): 477,3 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,53-EUR 7.57 (m, 4H), 7,44-of 7.48 (m, 6N), 7,09-7,13 (m, 3H), of 6.99 (d, 1H), 6.75 in (m, 2H), 6,62 (d, 1H), 3,60 (br m, 4H), of 3.12 (br m, 4H), 2,24 (s, 3H).

Example 56

Receiving (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-methanone

Method W

Benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (217 mg, 0.5 mmol), piperidine (46 is g, 0.55 mmol) and ethyldiethanolamine (0.1 ml, 0.6 mmol) was dissolved in dichloromethane (10 ml). The reaction mixture was stirred at room temperature for 4 h, and the solvent was evaporated. The residue was purified column chromatography on silica gel (20 g, eluent ethyl acetate)to give product as a white powder (135 mg, 70%).

MS (ISP): 386,4 (M+N+, 100), 771,3 (2M+H+, 25). NMR (300 MHz, DMSO-d6) ppm: 7,52-7,56 (m, 4H), 7,43-of 7.48 (m, 6N), 7,07 (d, 1H),? 7.04 baby mortality (s, 1H), 6.90 to (d, 1H), 3,40 (br m, 2H), 1,58 (br m, 2H), 1,48 (br m, 6N).

The following examples was carried out according to the method W:

Example 57

Receiving (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-o-tolyl-piperazine-1-yl)-methanone

From benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (87 mg, 0.2 mmol), hydrochloride of 1-(2-tolyl)piperazine (62 mg, 0.25 mmol) and ethyldiethanolamine (96 mg, 0.75 mmol) specified in the title compound was obtained as a pale yellow powder (1.1 mg, 1%).

MS (ISP): 477,3 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,53-EUR 7.57 (m, 4H), 7,44-7,47 (m, 6N), 7,09-7,14 (m, 4H), 6,91-7,03 (m, 3H), 3,61 (br m, 4H), 2,82 (br m, 4H), and 2.26 (s, 3H).

Example 58

Obtaining racemic ethyl ester 1-(2,2-diphenyl-benzo[1,3]dioxol-5-carbonyl)-piperidine-2-carboxylic acid

From benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (87 mg, 0.2 mmol), racemizes is ethylpiperidine (39 mg, 0.25 mmol) and ethyldiethanolamine (32 mg, 0.25 mmol) specified in the title compound was obtained as a white powder (to 22.6 mg, 24%).

MS (ISP): 458,4 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,53-7,56 (m, 4H), 7,43-7,49 (m, 6N), to 7.09 (d, 1H), 7,02 (s, 1H), 6,92 (d, 1H), 5,14 (br m, 1H), 4,16 (br kV, 2H), to 3.58 (br m, 1H), 3,12 (br m, 1H), 2,11 (br m, 1N), 1,18-to 1.63 (m, 9 H).

Example 59

Obtain [4-(2,3-dichloro-phenyl)-piperazine-1-yl]-(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-methanone

From benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (87 mg, 0.2 mmol), hydrochloride of 1-(2,3-dichlorophenyl)piperazine (66,9 mg, 0.25 mmol) and ethyldiethanolamine (64 mg, 0.50 mmol) specified in the title compound was obtained as a pale yellow powder (58,3 mg, 55%).

MC (ISP): 531,1 (M+H+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,53-EUR 7.57 (m, 4H), 7,44-of 7.48 (m, 6H), 7,31-7,33 (m, 2H). 7,11-7,14 (m, 2H), to 7.09 (d, 1H), 7,02 (d, 1H), 3,63 (br m, 4H), 2,98 (br m, 4H).

Example 60

Obtain [4-(4-chloro-3-trifluromethyl-phenyl)-piperazine-1-yl]-(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-methanone

From benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (87 mg, 0.2 mmol), 1-(4-chloro-3-trifluromethyl-phenyl)piperazine (66,2 mg, 0.25 mmol) and ethyldiethanolamine (32 mg, 0.25 mmol) specified in the title compound was obtained as a white powder (35,8 mg, 30%).

MS (ISP): 565,2 (M+N+, 100). NMR (300 MHz, LCA is-d 6) ppm: 7,52-7,58 (m, 4H), 7,44-7,49 (m, 7H), 7,27 (s, 1H), 7.23 percent (d, 1H), 7,13 (s, 1H), 7,10 (d, 1H), 7,00 (d, 1H), 3,60 (br m, 4H), of 3.28 (br m, 4H).

Example 61

Obtaining racemic (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(3-hydroxymethyl-piperidine-1-yl)-methanone

From benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (87 mg, 0.2 mmol), racemic 3-hydroxyethylpiperazine (28.8 mg, 0.25 mmol) and ethyldiethanolamine (32 mg, 0.25 mmol) specified in the title compound was obtained as a white powder (6.0 mg, 7%).

MS (ISP): 416,4 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,52-7,58 (m, 4H), 7,43-7,46 (m, 6H), 7,06 (d, 1H), 7,05 (s, 1H), 6,91 (d, 1H), 4,50 (br s, 1H, HE), of 3.32 (m, 2H), 2,45 (m, 2H), 1,10-of 1.78 (m, 7H).

Example 62

Receiving (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(2,3,5,6-tetrahydro-[1,2']bipyridinyl-4-yl)-methanone

From benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (87 mg, 0.2 mmol), 1-(2-pyrazinyl)piperazine (41,1 mg, 0.25 mmol) and ethyldiethanolamine (32 mg, 0.25 mmol) specified in the title compound was obtained as a white powder (19,0 mg, 20%).

MS (ISP): 465,3 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 8,31 (s, 1H), 8,13 (s, 1H), 7,86 (s, 1H), 7,53-EUR 7.57 (m, 4H), 7,44-of 7.48 (m, 6H), 7,14 (s, 1H), 7,11 (d, 1H), 7,01 (d, 1H), 3,61 (br m, 8H).

Example 63

Receiving (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-pyridin-2-yl-piperazine-1-yl)-methanone

From benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (87 mg, 0.2 mmol), 1-(2-pyridyl)piperazine (40,8 mg, 0.25 mmol) and ethyldiethanolamine (32 mg, 0.25 mmol) specified in the title compound was obtained as a white powder cases (53.2 mg, 57%).

MS (ISP): rub464.3 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 8,11 (m, 1H), 7,52-EUR 7.57 (m, 4H), 7,44-of 7.48 (m, 7H), 7,13 (s, 1H), 7,10 (d, 1H), 7,00 (d, 1H), PC 6.82 (d, 1H), only 6.64 (DD, 1H), 3,53 (br m, 8H).

Example 64

Receive (4-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-methyl-piperazine-1-yl)-methanone

Method Z.

4-Fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (336 mg, 1 mmol) was dissolved in dichloromethane (15 ml). Added EDCI (210 mg, 1.1 mmol) and 1-methyl-piperazine (220 mg, 2.2 mmol), the reaction mixture was stirred at room temperature for 5 hours the Reaction mixture was concentrated, and the residue was purified column chromatography on silica gel (20 g, eluent 5% methanol in dichloromethane)to give product as white crystals (150 mg, 37%).

MS (ISP): 419,4 (M+N+, 100), 460,5 (M+MeCN+H+, 70), 837,4 (2M+H+, 50). NMR (300 MHz, DMSO-d6) ppm: 7,52-7,58 (m, 4H), 7,46 is 7.50 (m, 6H), 7,01 (d, 1H), 6,92 (d, 1H), 3,60 (m, 2H), up 3.22 (m, 2H), 2,32 (m, 2H), 2,22 (m, 2H), 2,18 (s, 3H).

Getting 4-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid:

4-Fluoro-2,2-diphenyl-benzo[1,3]dioxol (5.8 g, 20 mmol) was dissolved in THF (40 ml). The reaction mixture was cooled to -78° C in argon atmosphere. Added TMEDA (2.9 ml, 20 mmol)was then added dropwise n-butyl lithium (12,5 ml of 1.6 n solution in hexane). The reaction mixture was stirred at a temperature of -78°C for 2 h Then at the same temperature was added carbon dioxide (20 g). The reaction mixture was left to warm up to the temperature 0°and poured into water (80 ml). The reaction mixture was twice extracted with ethyl acetate. The aqueous fraction was neutralized by adding 1 N. aqueous HCl solution was twice extracted with ethyl acetate. The organic fraction was washed with a saturated solution of sodium chloride, dried over sodium sulfate and was filtered. The solvent was evaporated, and the residue is suspended in n-hexane, stirred for 10 min, and the product was filtered, receiving acid as a white powder (4.0 g, 60%). tPL: 189-191°C.

Getting 4-fluoro-2,2-diphenyl-benzo[1,3]dioxole:

3-Formeterol (12,81 g, 100 mmol) and dichlorodiphenylmethane (23,71 g, 100 mol) was dissolved in toluene (250 ml), the reaction mixture is boiled under reflux during the night. The solvent was evaporated and the residue was purified by chromatography on silica gel (200 g, eluent 1/1 dichloromethane/n-hexane)to give ketal in the form of white crystalline powder (26,74 g, 91%). tPL: 65-67°C.

The following examples was performed using method C:

Example 65

Receive (4-fluoro-22-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanone

From 4-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (336 mg, 1 mmol), EDCI (210 mg, 1.1 mmol) and research (190 mg, 2.2 mmol) specified in the title compound was obtained as a white powder (183 mg, 46%). Chromatographic purification was performed on silica gel (20 g, eluent 5% methanol in dichloromethane).

MS (ISP): to 406.4 (M+N+, 100), 811,2 (2M+H+, 25). NMR (300 MHz, DMSO-d6) ppm: 7,54-7,58 (m, 4H), 7,46 is 7.50 (m, 6H), 7,01 (d, 1H), of 6.96 (d, 1H), 3,63 (m, 4H), 3,52 (m, 2H), 3.27 to (m, 2H).

Example 66

Receive (4-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanone

From 4-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (336 mg, 1 mmol), EDCI (210 mg, 1.1 mmol) and piperidine (187 mg, 2.2 mmol) specified in the title compound was obtained as a white powder (103 mg, 26%). Chromatographic purification was performed on silica gel (20 g, eluent 5% methanol in dichloromethane).

MC (ISP): 404,5 (M+H+, 100), 807,4 (2M+N+, 30). NMR (300 MHz, DMSO-d6) ppm: of 7.48-7,56 (m, 4H), 7,42-of 7.48 (m, 6H), 6,98 (d, 1H), 6.89 in (d, 1H), to 3.58 (m, 2H), 3,20 (m, 2H), 1,46-of 1.62 (m, 4H), 1,38 of 1.46 (m, 2H).

Example 67

Receiving (4,7-dichloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanone

From 4,7-dichloro-2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (154 mg, 0.4 mmol), EDCI (84 mg, 0.44 mmol) and piperidine (75 mg, 0.88 mmol) specified in the header is connected to the e was obtained as a white powder (27 mg, 15%). Chromatographic purification was performed on silica gel (20 g, eluent ethyl acetate).

MC (ISP): 454,4 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: of 7.48-of 7.55 (m, 10H), to 7.09 (s, 1H), to 3.58 (m, 2H), 3,14 (m, 2H), 1,48 is 1.60 (m, 4H), to 1.38 to 1.48 (m, 2H).

Getting 4,7-dichloro-2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid:

2,5-Dichloro-3,4-dihydroxybenzoic acid (1 g, 4,48 mmol) and dichlorodiphenylmethane (2,12 g, 9,96 mmol) was dissolved in toluene (40 ml), the reaction mixture is boiled under reflux for 24 hours After cooling, the reaction mixture was evaporated the solvent, the residue was purified column chromatography on silica gel (100 g, eluent dichloromethane, then 5% methanol in dichloromethane)to give the acid as white crystals (490 mg, 28%).

MC (ISN): 385,0 (M-N+, 100). NMR (300 MHz, DMSO-d6) ppm: 13,47 (br s, 1H, HE), to 7.59 (s, 1H), 7,54 (br m, 10 H).

Obtaining 2,5-dichloro-3,4-dihydroxybenzoic acid described in the prior art (EP 416410).

Example 68

Receiving (4,7-dichloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanone

From 4,7-dichloro-2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (154 mg, 0.4 mmol), EDCI (84 mg, 0.44 mmol) and research (77 mg, 0.88 mmol) specified in the title compound was obtained as a white powder (88 mg, 49%). Chromatographic purification was performed on silica gel (20 g, eluent ethyl acetate).

MS (ISP): 456,4 (M+N+, 100). NMR (300 MHz, the MCO-d 6) ppm: 7,52 (m, 10H), to 7.15 (s, 1H), 3,45-and 3.72 (m, 6H), 3,20 (m, 2H).

Example 69

Receiving (4,7-dichloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-methyl-piperazine-1-yl)-methanone

From 4,7-dichloro-2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (115 mg, 0.3 mmol), EDCI (63 mg, 0.33 mmol) and N-methylpiperazine (66 mg, 0.66 mmol) specified in the title compound was obtained as a white powder (28 mg, 20%). Chromatographic purification was performed on silica gel (20 g, eluent 5% methanol in dichloromethane).

MS (ISP): 469,1 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,52 (m, 10H), 7,10 (s, 1H), 3,44-3,68 (m, 2H), 3,18 (m, 2H), 2,20-2,40 (m, 4H), to 2.18 (s, 3H).

Example 70

Obtaining (7-bromo-4-chloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-methyl-piperazine-1-yl)-methanone

From 7-bromo-4-chloro-2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (100 mg, 0.23 mmol), EDCI (49 mg, 0.25 mmol) and N-methylpiperazine (50 mg, 0.50 mmol) was obtained from (7-bromo-4-chloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-methyl-piperazine-1-yl)-methanon in the form of a white powder (9 mg, 8%). Chromatographic purification was performed on silica gel (20 g, eluent 5% methanol in dichloromethane).

MS (ISP): 513,1 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,52 (m, 10H), 7,18 (s, 1H), 3,44-3,68 (m, 2H), 3,17 (m, 2H), 2,20-2,40 (m, 4H), of 2.09 (s, 3H).

Obtain 7-bromo-4-chloro-2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid:

Methyl ester of 7-bromo-4-chloro-2,2-define is-benzo[1,3]dioxol-5-Carboni acid (520 mg, to 1.16 mmol) was dissolved in THF (6 ml). Was added a solution of hydrate of lithium hydroxide (190 mg, with 4.64 mmol) in water (6 ml). After adding methanol (2 ml) the reaction mixture is boiled under reflux for 5 hours After cooling, the organic solvent was evaporated and the reaction mixture was diluted with water, acidified 1 N. aqueous solution of HCl and was extracted with ethyl acetate. Combined organic fractions were washed with a saturated solution of sodium chloride, dried over sodium sulfate and was filtered. The solvent was evaporated in vacuum. The residue was stirred with n-hexane. The product was precipitated as a white powder (350 mg, 70%)which was filtered and dried.

MS (ISP): 429,1 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 13,45 (br s, 1H, HE), 7,68 (s, 1H), 7,52 (m, 10H).

Obtain methyl ester of 7-bromo-4-chloro-2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid described in the prior art (EP 0544166).

Example 71

Obtaining (7-bromo-4-chloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanone

From 7-bromo-4-chloro-2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (100 mg, 0.23 mmol), EDCI (49 mg, 0.25 mmol) and piperidine (50 mg, 0.50 mmol) specified in the title compound was obtained as a white powder (7 mg, 7%). Chromatographic purification was performed on silica gel (20 g, eluent ethyl acetate).

MS (ISP): 498,1 (M+N+6) ppm: 7,52 (m, 10H), 7,17 (s, 1H), of 3.56 (m, 2H), 3,12 (m, 2H), 1,48 is 1.60 (m, 4H), 1,40-1,482,09 (m, 2H).

Example 72

Obtaining (7-bromo-4-chloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanone

From 7-bromo-4-chloro-2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (100 mg, 0.23 mmol), EDCI (49 mg, 0.25 mmol) and research (44 mg, 0.50 mmol) specified in the title compound was obtained as a white powder (47 mg, 39%). Chromatographic purification was performed on silica gel (20 g, eluent ethyl acetate).

MS (ISP): 500,1 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,52 (m, 10H), of 7.23 (s, 1H), 3,42-3,70 (m, 6H), 3,19 (m, 2H).

Example 73

Obtaining (7-hydroxy-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanone

Piperidine (0.3 ml, 2 mmol) and ethyldiethanolamine (0.5 ml, 3 mmol) was dissolved in dichloromethane (10 ml). At room temperature was added dropwise a solution of 7-hydroxy-2,2-diphenyl-benzo[1,3]dioxol-5-carbonylchloride (353 mg, 1 mmol) in dichloromethane (3 ml). The reaction mixture was stirred at room temperature for 24 h the solvent was Evaporated, and the residue was transferred into a mixture of ethyl acetate-water. The organic fraction was extracted with 1 N. aqueous solution of HCl, a saturated solution of sodium chloride, dried over sodium sulfate and was filtered. The solvent was evaporated, and the residue was purified Colo is face-to-face chromatography on silica gel (20 g, eluent 5% methanol in dichloromethane)to give phenol as a white powder (180 mg, 45%).

MS (ISP): 400,3 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 10,08 (s, 1H, HE), 7,52-of 7.55 (m, 4H), 7,41-of 7.48 (m, 6H), of 6.52 (s, 1H), 6,46 (s, 1H), 3,38 (br m, 4H), 1,59 (br m, 2H), 1,09 (br m, 4H).

Obtain 7-hydroxy-2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid described in the prior art (.S. Feldman, S.M. Ensel, J. Am. Chem. Soc. 115 (3) (1993) 1162-3).

Obtain 7-hydroxy-2,2-diphenyl-benzo[1,3]dioxol-5-carbonylchloride:

7-Hydroxy-2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (334 mg, 1 mmol) was dissolved in chloroform (5 ml). Added 1 drop of triethylamine. At a temperature of 45-50°C for 30 minutes was added thionyl chloride (0.33 ml, 4.5 mmol). The reaction mixture was stirred for 6 hours at a temperature of 70°C. the Excess thionyl chloride was removed by evaporation. The resulting crude 7-hydroxy-2,2-diphenyl-benzo[1,3]dioxol-5-carbonylchloride without further purification was used in the next stage of the synthesis.

Example 74

Obtaining 1-(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-carbonyl-4-(4-fluoro-phenyl)-1,2,3,6-tetrahydro-pyridine

The hydrochloride of 4-(4-forefeel)-1,2,3,4-tetrahydropyridine (106 mg, 0.5 mmol) suspended in dichloromethane (10 ml). Added ethyldiethanolamine (150 mg, 1.2 mmol) and then benzotriazol-1 silt ether of 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (150 mg, 0.5 mmol). The reaction mixture is eremetical at room temperature for 2 hours The solvent was evaporated, the residue was purified column chromatography on silica gel (20 g, eluent ethyl acetate). Amide was obtained as white crystals (177 mg, 75%).

MS (ISP): 478,4 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,53-EUR 7.57 (m, 4H), 7,44 is 7.50 (m, 8H), 7,17 (Tr, 2H), 7,15 (s, 1H), 7,10 (d, 1H), 7,01 (d, 1H), x 6.15 (br s, 1H), 4,15 (br s, CH2), 3,62 (m, 2H), 2,52 (m, 2H, under DMSO peak).

Example 75

Obtaining 1-(2,2-diphenyl-benzo[1,3]dioxol-5-yl-methyl)-4-(4-fluoro-phenyl)-1,2,3,6-tetrahydro-pyridine

Socialogical (13 mg, 0.36 mmol) suspended in THF (10 ml). In the atmosphere of argon at room temperature was added dropwise a solution of (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-[4-(4-fluoro-phenyl)-3,6-dihydro-2H-pyridine-1-yl]-methanone (104 mg, 0.22 mmol) in THF (1.5 ml). The reaction mixture is boiled under reflux for 2 hours was Added socialogical (50 mg)and the reaction mixture is boiled under reflux in an argon atmosphere overnight. Solution was added to lydialydia (0.3 ml, 1 M solution in THF)and the reaction mixture is boiled under reflux for 4 hours the Reaction mixture was cooled (ice bath) and in argon atmosphere was slowly added a mixture of water (0.4 ml) and THF (1.5 ml). The reaction mixture was stirred for 10 min, and added solid potassium carbonate (2 g). The reaction mixture was filtered and the mother liquor is concentrated is in vacuum. The residue was dissolved in ethyl acetate. The organic solution was dried over sodium sulfate, filtered and evaporated the solvent, obtaining the product as a colourless viscous oil (85 mg, 85%).

MS (ISP): 464,4 (M+N+, 100). NMR (300 MHz, DMSO-d6) ppm: 7,52-7,56 (m, 4H), 7,42-7,53 (m, 7H), 7,14 (Tr, 2H), 6,98 (m, 2H), 6.87 in (s, 1H), 6,83 (d, 1H), 6,09 (br s, 1H), 3,48 (s, CH2), a 3.01 (m, 2H), 2,59 (m, 2H), 2,52 (m, 2H).

Example 78

Obtaining N-(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-benzosulfimide

2,2-Diphenyl-1,3-benzodioxol-5-amine was dissolved in dichloromethane (5 ml). Was added N-ethyldiethanolamine (0.1 ml, 0.6 mmol) and benzosulphochloride (88 mg, 0.5 mmol). The reaction mixture was stirred for 5 h at room temperature. The reaction mixture was washed with cold 1 N. aqueous solution of HCl, 1 N. aqueous solution of NaOH and a saturated solution of sodium chloride. The organic fraction was dried over sodium sulfate, was filtered, and the solvent was evaporated in vacuum. The residue was purified column chromatography, as the eluent used dichloromethane. The product was led from hexane, obtaining N-(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-benzosulfimide in the form of white crystals (12 mg, 6%).

MS: 428,3 ([M-H]-).

NMR (300 MHz, DMSO-d6) ppm: of 10.05 (br, 1H, NH), of 7.69 (d, 2H), to 7.59 (d, 1H), 7,55 (d, 2H), 7,50-7,38 (m, 10H), 6.87 in (d, 1H), 6.73 x (s, 1H), 6,50 (d, 1H).

The following examples 79-86 (excluding the rising of Example 82) was performed according to the method, described in example 78:

Example 79

Obtaining N,N-bis(methylsulphonyl)-2,2-diphenyl-1,3-benzodioxol-5-amine

Specified in the title compound was obtained in accordance with the General procedure described in example 78, based on 2,2-diphenyl-1,3-benzodioxol-5-amine and methanesulfonanilide.

Colorless powder.

MS: m/e=KZT 446.4 ([M+H]+).

NMR (300 MHz, DMSO-d6) ppm: 7,44-7,58 (m, 10H), 7,28 (s, 1H), 7,13 (d, 1H), 7,06 (d, 1H), 3,49 (s, 6H).

Example 80

Obtaining N,N-bis(butylsulfonyl)-2,2-diphenyl-1,3-benzodioxol-5-amine

Specified in the title compound was obtained in accordance with the General procedure described in example 78, based on 2,2-diphenyl-1,3-benzodioxol-5-amine and butanesulfinamide.

MS: m/e=530,4 ([M+H]+).

NMR (300 MHz, DMSO-d6) ppm: 7,44-7,58 (m, 10H), 7,22 (s, 1H), 7,12 (d, 1H), 7,03 (d, 1H), 3.62 rubles (br, 4H), 1,71 (m, 4H), of 1.40 (m, 4H), to 0.88 (t, 6H).

Example 81

Receiving (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-amide cyclohexanecarbonyl acid

Specified in the title compound was obtained in accordance with the General procedure described in example 78, based on 2,2-diphenyl-1,3-benzodioxol-5-amine and acid chloride cyclohexanecarbonyl acid.

MS: m/e=400,5 ([M+H]+).

NMR (300 MHz, DMSO-d6) ppm: 9,71 (br, 1H, NH), 7,41-7,56 (m, 11N), 6,97 (d, 1H), 6,92 (d, 1H), 2,23 (br, 1H), 1.60-to 180 (m, 10H), 1,18-of 1.42 (m, 10H).

Example 82

Receiving (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-amide butane-1-sulfonic acid

N,N-Bis(butylsulfonyl)-2,2-diphenyl-1,3-benzodioxol-5-amine (example 80, 79 mg, 0.15 mmol) was dissolved in THF (4 ml). At room temperature was added dropwise a solution of tetrabutylammonium fluoride in THF (1 M, 0.16 ml, 0.16 mmol), the reaction mixture was stirred at room temperature overnight. The reaction mixture is boiled under reflux for 30 min, poured into water and was extracted twice with ethyl acetate. The organic fractions were combined, washed with saturated aqueous sodium chloride, dried over sodium sulfate, filtered and the solvent was evaporated in vacuum. The residue was purified column chromatography, using as eluent dichloromethane. After crystallization from hexane, the product was obtained as white crystals (45 mg, 74%).

ISN-MS: m/e=408,2 ([M+H]-, 100).

NMR (300 MHz, DMSO-d6) ppm: at 9.53 (br, 1H, NH), 7,55-7,42 (m, 10H), 6,98 (d, 1H), 6.90 to (s, 1H), 6,69 (d, 1H), 3,00 (m, 2H), 1,59 (m, 2H), 0,804 (t, 3H).

Example 83

Obtaining N-(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-butyramide

Specified in the title compound was obtained in accordance with the General procedure described in example 78, based on 2,2-diphenyl-1,3-benzodioxol-5-amine and chlorohydrination acid.

MS: m/e=360,3 ([M+H]+).

NMR (300 MHz, DMSO-d6) ppm: 9,78 (br, 1H, NH), 7,41-of 7.55 (m, 11H), 6,94 (m, 2H), 2,22 (t, 2H), 1,59 (m, 2H), 0,89 (t, 3H).

Example 84

Receiving (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-amide morpholine-4-carboxylic acid

Specified in the title compound was obtained in accordance with the General procedure described in example 78, based on 2,2-diphenyl-1,3-benzodioxol-5-amine and 4-morpholinylcarbonyl.

MS: m/e=403,4 ([M+H]+).

NMR (300 MHz, DMSO-d6) ppm: to 8.41 (br, 1H, NH), 7,40-of 7.55 (m, 10H), 7,21 (s, 1H), 6.89 in (d, 1H), 6,83 (d, 1H), to 3.58 (m, 4H), 3,37 (m, 4H).

Example 85

Receiving (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-amide piperidine-1-sulfonic acid

Specified in the title compound was obtained in accordance with the General procedure described in example 78, based on 2,2-diphenyl-1,3-benzodioxol-5-amine and piperidine-1-sulphonylchloride.

MS: m/e=435,3 ([M+H]+).

NMR (300 MHz, DMSO-d6) ppm: 9,62 (br, 1H, NH), 7,41-of 7.55 (m, 10H), 6,97 (d, 1H), 6.87 in (s, 1H), of 6.68 (d, 1H), 3.04 from (m, 4H), to 1.37 (m, 6H).

Example 86

Receiving (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-amide piperidine-1-carboxylic acid

Specified in the title compound was obtained in accordance with the General procedure described in example 78, based on 2,2-diphenyl-1,3-benzodioxol-5-amine and piperidinecarbonitrile.

MS: m/e=401,4 ([M+H] ).

NMR (300 MHz, DMSO-d6) ppm: 8,30 (br, 1H, NH), 7,40-of 7.55 (m, 10H), 7,22 (d, 1H), 6,84 (m, 2H), 3,36 (m, 2H), 1,45-of 1.56 (m, 6H).

Example 87

Obtaining [2-(4-chloro-phenyl)-2-(2-fluoro-4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

a) Obtaining (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanone

To a mixture of 1H-benzotriazol-1-yl-2,2-diphenyl-1,3-benzodioxol-5-carboxylate (300 mg, 0,689 mmol) in acetonitrile (2.0 ml) at a temperature of 0°With added morpholine (100 mg, 1.15 mmol, 1,67 EQ.). After 10 min remove the cooling bath and the reaction mixture was stirred at a temperature of 20°C for 3 hours, the Reaction mixture was transferred into a mixture of water-dichloromethane. The aqueous fraction was extracted with dichloromethane. The organic fractions were combined, washed with saturated aqueous sodium chloride, water, and then evaporated in vacuum, obtaining the product as a white powder (267 mg, quantitative yield).

MS: m/e=of 388.4 ([M+H]+).

1H-Benzotriazol-1-yl-2,2-diphenyl-1,3-benzodioxol-5-carboxylate was obtained as described in the prior art methods (EP 544166).

b) Receiving (3,4-dihydroxy-phenyl)-morpholine-4-yl-methanone

It cooled down to 0°With the solution of (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanone (270 mg, 0.7 mmol) in triperoxonane acid (4 ml) was added triethylsilane (160 mg, 1.38 mmol, 1,96 EQ.). The reaction mixture is stirred at a temperature of 0° For 20 minutes the Cooling bath was removed and the reaction mixture was stirred at room temperature for 4 hours the Solvent was evaporated. The residue was purified by the method of accelerated chromatography, getting mentioned in the title compound as a white powder (147 mg, 95%).

MS: m/e=to 220.3 ([M-H]-).

C) Getting (4-chloro-phenyl)-(2-fluoro-4-methoxy-phenyl)-methanone

It cooled down to 0°With nitrobenzene (450 ml) was added trichloride aluminum (144 g of 1.08 mol). Was slowly added a solution of 4-chlorobenzylchloride (128,5 ml, 1 mol) in nitrobenzene (200 ml), then was slowly added 3-Floransa (108,5 ml, 0.95 mol). The reaction mixture was stirred at a temperature of 20°during the night, then was transferred into a mixture of water with ice - ethyl acetate. The aqueous fraction was extracted with ethyl acetate, and the organic fractions were combined, washed with water, dried over sodium sulfate, filtered and concentrated in vacuum. The warm solution was poured into cyclohexane. The precipitation was filtered, washed with cyclohexane and dried in vacuum, obtaining mentioned in the title compound as colorless powder (104,5 g, 41%).

MS: m/e=264 ([M]+).

g) Receiving 4-chloro-2'-fluoro-4'-methoxy-dichlorodiphenylmethane

To a solution of (4-chloro-phenyl)-(2-fluoro-4-methoxy-phenyl)-methanone (106 mg, 0.4 mmol, 1 EQ.) in thionyl chloride (0.6 ml) was added N,N-dimetil is mamid (0,031 ml, 0.4 mmol, 1 EQ.). The reaction mixture under stirring was boiled under reflux for 18 h, and volatile components were removed in vacuum, obtaining mentioned in the title compound as an orange oil (135 mg, 87%).

NMR (300 MHz, CDCl3) ppm: of 7.82 (DD, 1H), 7,56 (d, 2H), 7,32 (DD, 2H), 6.73 x (DD, 1H), 6,63 (DD, 1H), 3,83 (s, 3H).

d) [2-(4-chloro-phenyl)-2-(2-fluoro-4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

A solution of (3,4-dihydroxy-phenyl)-piperidine-1-yl-methanone (of 37.7 mg, 0,169 mmol) and 2-fluoro-4-methoxy-4'-chlorodiphenylmethane (67.5 mg, 0,175 mmol) in toluene (1.7 ml) was boiled under reflux for 42 h, the Reaction mixture was cooled and adsorbing on silica gel. After purification by the method of accelerated chromatography indicated in the title compound was obtained as a yellow semi-solid powder (46 mg, 58%).

MS: m/e=470,2 ([M+H]+).

Example 88

Getting 4-[2-(4-chloro-phenyl)-2-(2-fluoro-4-methoxy-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-research

a) Obtaining 4-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-research

To a solution of [3,4-[(diphenylmethylene)dioxy]phenyl]sulphonylchloride (202 mg, 0.54 mmol) in THF (2 ml) was added morpholine (52 mg, 0,596 mmol, 1.1 EQ.) and tert-piperonyl potassium (73 mg, of 0.65 mmol, 1.2 EQ.). The reaction mixture was stirred at 20°C for 48 h, transferred into a mixture of dichloromethane - 1 N. in the hydrated solution of HCl. The aqueous fraction was extracted with dichloromethane. The organic fractions were combined, washed with aqueous sodium bicarbonate solution and saturated aqueous sodium chloride. After purification by the method of accelerated chromatography indicated in the title compound was obtained as a colourless powder (179 mg, 78%).

MS: m/e=424,5 ([M+H]+).

[3,4-[(Diphenylmethylene)dioxy]phenyl]sulphonylchloride was obtained as described in the prior art methods (EP 544166 and WO 9218490).

b) Obtaining 4-(morpholine-4-sulfonyl)-benzene-1,2-diol

Specified in the title compound was obtained in accordance with the General procedure described in example b on the basis of 4-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-research (example a). Colorless powder.

MS: m/e=257,9 ([M-H]).

C) Obtaining 4-[2-(4-chloro-phenyl)-2-(2-fluoro-4-methoxy-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-research

Specified in the title compound was obtained in accordance with the General procedure described in example d on the basis of 4-(morpholine-4-sulfonyl)-benzene-1,2-diol (example 88B) and 2-fluoro-4-methoxy-4'-chlorodiphenylmethane (example 87 g). White powder.

MS: m/e=506,9 ([M+H]+).

Example 89

Obtaining [2-(4-methoxy-phenyl)-2-(3-nitro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

a) Getting (4-methoxyphenyl)-(3-nitrophenyl)-methanone

To a cooled to the temperature 0° With a mixture of anisole (17,7 ml, rate £ 0.162 mol, 1.0 EQ.) and trichloride aluminum (26,9 g, 0,202 mol, 1.25 EQ.) in 1,2-dichloroethane (140 ml) was slowly added 3-nitrobenzoate (30 g, rate £ 0.162 mol). Removed the cooling bath and the reaction mixture was stirred at 20°C for 2 h, the Reaction mixture was poured into ice-cold water. Added concentrated hydrochloric acid (5 ml). The aqueous fraction was extracted with dichloromethane (2 times). The organic fractions were combined, dried over sodium sulfate, filtered, and volatile components were removed in vacuum. After purification by the method of accelerated chromatography indicated in the title compound was obtained as an orange powder (35.1 g, 84%), tPL: 88-89°C.

b) Obtaining 4-methoxy-3'-nitro-dichlorodiphenylmethane

Specified in the title compound was obtained in accordance with the General procedure described in example g on the basis of (4-methoxyphenyl)-(3-nitrophenyl)-methanone (example 89a). A yellow oil.

NMR (300 MHz, CDCl3) ppm: 8,53-charged 8.52 (m, 1H), 8,23 (DD, 1H), 7,95 (DD, 1H), to 7.59-to 7.50 (m, 3H), 6.89 in (d, 2H), 3,85 (s, 3H).

C) Obtaining [2-(4-methoxy-phenyl)-2-(3-nitro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example d on the basis of (3,4-dihydroxy-phenyl)-morpholine-1-yl-methanone (example b) and 4-methoxy-3'-nitro-dichlorodiphenylmethane (example 89 is). The white foam.

MS: m/e=463,3 ([M+H]+).

Example 90

Obtaining [4-[2-(4-methoxy-phenyl)-2-(3-nitro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-research

Specified in the title compound was obtained in accordance with the General procedure described in example 108b, on the basis of 4-(morpholine-4-sulfonyl)-benzene-1,2-diol (example 88B) and 4-methoxy-3'-nitro-dichlorodiphenylmethane (example b). Light yellow oil.

MS: m/e=499 ([M+H]+).

Example 91

Obtaining [4-[2-(4-methoxy-phenyl)-5-(morpholine-4-carbonyl)-benzo[1,3]dioxol-2-yl]-benzonitrile

a) Obtaining 4-(4-methoxy-benzoyl)-benzonitrile

Specified in the title compound was obtained in accordance with the General method described in example 87 g, on the basis of 4-(4-methoxy-benzoyl)-benzonitrile. A yellow oil.

NMR (300 MHz, CDCl3) ppm: 7,70-of 7.60 (m, 4H), 7,43 (d, 2H), PC 6.82 (d, 2H), of 3.77 (s, 3H).

b) Obtain 4-cyano-4-methoxy-dichlorodiphenylmethane

Specified in the title compound was obtained in accordance with the General procedure described in example g on the basis of 4-(4-methoxy-benzoyl)-benzonitrile (example a). A yellow oil.

MS: m/e=443,4 ([M+H+]).

C) Obtaining 4-[2-(4-methoxy-phenyl)-5-(morpholine-4-carbonyl)-benzo[1,3]dioxol-2-yl]-benzonitrile

Specified in the title compound was obtained in accordance with the General method described in the example d, on the basis of (3,4-dihydroxy-phenyl)-morpholine-1-yl-methanone (example b) and 4-cyano-4-methoxy-dichlorodiphenylmethane (example b). A yellow oil.

MS: m/e=443,4 ([M+H]+).

Example 92

Getting 4-[2-(4-methoxy-phenyl)-5-(morpholine-4-sulfonyl)-benzo[1,3]dioxol-2-yl]-benzonitrile

The compound was obtained in accordance with the General procedure described in example V on the basis of 4-(morpholine-4-sulfonyl)-benzene-1,2-diol (example 88B) and 4-cyano-4-methoxy-dichlorodiphenylmethane (example b). Colorless foam.

MS: m/e=479,3 ([M+H]+).

Example 93

Obtaining [2-(2-fluoro-4-methoxy-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

a) Getting (2-fluoro-4-methoxy-phenyl)-(4-fluoro-phenyl)-methanone

It cooled down to 5°With a mixture of trichloride aluminum (144 g of 1.08 mol, of 1.13 EQ.) in nitrobenzene (450 ml) was slowly added a solution of 4-forobulgaria (120 ml, 1 mol, of 1.05 equiv.) in nitrobenzene (200 ml). To the reaction mixture was slowly added 3-Floransa (108,5 ml, 0.95 mol). Removed the cooling bath and the reaction mixture was stirred at a temperature of 20°C for 3 h and poured into water with ice. The aqueous fraction was extracted with dichloromethane (twice). The organic fractions were combined, dried over sodium sulfate, filtered, and volatile components were removed in VA is uume. The crude mixture was led from cyclohexane, the precipitation was filtered and washed with cyclohexane. The precipitate was dried in vacuum, obtaining mentioned in the title compound as a white powder (57,78 g, 25%).

tPL: 89,7-90,1°C.

b) Obtain 2-fluoro-4-methoxy-4'-fluoro-dichlorodiphenylmethane

Specified in the title compound was obtained in accordance with the General procedure described in example g on the basis of (2-fluoro-4-methoxy-phenyl)-(4-fluoro-phenyl)-methanone (example 93A). Yellow semi-solid powder.

MS: m/e=304,2 ([M+H]+).

C) Obtaining [2-(2-fluoro-4-methoxy-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example d on the basis of (3,4-dihydroxy-phenyl)-morpholine-1-yl-methanone (example b) and 2-fluoro-4-methoxy-4'-fluoro-dichlorodiphenylmethane (example b). Brown butter.

MS: m/e=454,5 ([M+H]+).

Example 94

Getting 4-[2-(2-fluoro-4-methoxy-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-research

Specified in the title compound was obtained in accordance with the General procedure described in example V on the basis of 4-(morpholine-4-sulfonyl)-benzene-1,2-diol (example 88B) and 2-fluoro-4-methoxy-4'-fluoro-dichlorodiphenylmethane (example b). The white foam.

MS: m/e=490,3 ([M+H]+).

P the emer 95

Obtain (6-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanone

a) Obtaining 2-fluoro-4,5-dihydroxy-benzaldehyde

It cooled down to -78°With a solution of 6-forevertron aldehyde (2 g, 10.9 mmol) in dichloromethane (40 ml) was added a solution of tribromide boron in dichloromethane (1 M, 44 ml, 44 mmol, 4.0 EQ.). The reaction mixture was left to warm to room temperature and was stirred overnight. The reaction mixture was transferred into a mixture of diethyl ether - water with ice. The aqueous fraction was extracted with diethyl ether. The organic fractions were combined, washed with water, dried over sodium sulfate and was filtered. Volatile components were removed in vacuum. After purification by the method of accelerated chromatography indicated in the title compound was obtained as a dark powder (1,71 mg, quantitative yield).

MS: m/e=156,0 ([M]+).

b) Obtaining 4,5-bis-benzyloxy-2-fluoro-benzaldehyde

To a solution of 2-fluoro-4,5-dihydroxy-benzaldehyde (44,0 g, 282 mmol) in acetone (1 l) was added potassium carbonate (39,0 g, 0,282 mmol, 1.0 EQ.) and benzylbromide (33,5 ml, 0,282 mmol, 1.0 EQ.). The reaction mixture was stirred at 20°With during the night. The reaction mixture was filtered through a layer dicalite. After evaporation and purification by the method of accelerated chromatography specified in the header connect the tion was obtained as a white powder (5.34 g, 6%).

MS: m/e=336,1 ([M]).

C) Obtaining 4,5-bis-benzyloxy-2-fluoro-benzoic acid

To a cooled to 0°With a solution of 4,5-bis-benzyloxy-2-fluoro-benzaldehyde (2.15 g, to 6.39 mmol) in acetone (86,0 ml) was slowly added Jones reagent (4.3 ml). The reaction mixture was stirred at a temperature of 0°C for 19 h To the reaction mixture were added propanol (0,43 ml) and stirred at 20°C for 40 minutes the resulting crude mixture was filtered, washed with acetone and poured into water (50 ml). The precipitation was filtered, washed with water and dried in vacuum, obtaining mentioned in the title compound as a white powder (1,82 g, 81%).

MS: m/e=351,1 ([M-H]+),

The Jones reagent: to a cooled to 0°With a solution of chromium oxide (826 mg, 8.3 mmol) in water (1.3 ml) was slowly added concentrated sulfuric acid (0,86 ml). The resulting solution was diluted with water (2,15 ml).

g) Receiving (4,5-bis-benzyloxy-2-fluoro-phenyl)-piperidine-1-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example d on the basis of 4,5-bis-benzyloxy-2-fluoro-benzoic acid (example V) and piperidine. White powder.

MS: m/e=420,5 ([M+H]+).

d) Obtaining (2-fluoro-4,5-dihydroxy-phenyl)-piperidine-1-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in PR is as b, on the basis of (4,5-bis-benzyloxy-2-fluoro-phenyl)-piperidine-1-yl-methanone (example g). Colorless semi-solid powder.

MS: m/e=240,2 ([M+H]+).

e) Getting (6-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 108b, on the basis of (2-fluoro-4,5-dihydroxy-phenyl)-piperidine-1-yl-methanone (example d) and dichlorodiphenylmethane. Colorless semi-solid powder.

MS: m/e=404,3 ([M+H]+).

Example 96

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 108b, on the basis of (2-fluoro-4,5-dihydroxy-phenyl)-piperidine-1-yl-methanone (example d) and 2,4-dichloro-4'-fluoro-chlorodiphenylmethane (example b). White powder.

MS: m/e=404,3 ([M-C5H10N*]+).

Example 97

Obtaining [6-fluoro-2-(4-fluoro-phenyl)-2-phenyl-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

a) Obtaining 4-fortifiediron

Specified in the title compound was obtained in accordance with the General procedure described in example b based on benzotrifluoride and vorobtsova. A yellow oil.

NMR (300 MHz, CDCl3) ppm: 7,63-EUR 7.57 (m, 4H),7,38-7,35 (m, 3H), 7,06-7,00 (m, 2H).

b) Receiving [6-fluoro-2-(4-fluoro-phenyl)-2-phenyl-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 108b, on the basis of (2-fluoro-4,5-dihydroxy-phenyl)-piperidine-1-yl-methanone (example d) and 4-fortifiediron (example 97A). White powder.

MS: m/e=422,2 ([M+H]+).

Example 98

Obtaining [2-(2-chloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

a) Obtaining 2-chloro-4'-methoxy-diphenyldichlorosilane

Specified in the title compound was obtained in accordance with the General procedure described in example b, based on 2-chlorobenzotrifluoride and anisole. Brown butter.

NMR (300 MHz, CDCl3) ppm: 7,46-7,35 (m, 6H), 6,85 (d, 2H), 3,83 (s, 3H).

b) Receiving [2-(2-chloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 108b, on the basis of [2-(2-chloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone (example d) and 2-chloro-4'-methoxy-diphenyldichlorosilane (example 98A). White powder.

MS: m/e=468,1 ([M+H]+).

Example 99

Obtain (6-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanone

a) Obtaining (4,5-bis-benzyloxy-2-fluoro-phenyl)-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example d on the basis of 4,5-bis-benzyloxy-2-fluoro-benzoic acid (example V) and research. White powder.

MS: m/e=421,1 ([M+H]+).

b) Receiving (2-fluoro-4,5-dihydroxy-phenyl)-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example b on the basis of (4,5-bis-benzyloxy-2-fluoro-phenyl)-morpholine-4-yl-methanone (example 99a). White powder.

MS: m/e=242,2 ([M+H]+).

C) Getting (6-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 108b, on the basis of (2-fluoro-4,5-hydroxy-phenyl)-morpholine-4-yl-methanone (example b) and dichlorodiphenylmethane. White powder.

MS: m/e=406,2 ([M+H]+).

Example 100

Obtaining [6-fluoro-2-(4-fluoro-phenyl)-2-phenyl-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 108b, on the basis of (2-fluoro-4,5-dihydroxy-phenyl)-morpholine-4-yl-methanone (example b) and 4-fortifiediron (example 97A). White powder.

MS: m/e=424,3 ([M+H]+).

p> Example 101

Obtaining [2-(2-chloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 108b, on the basis of (2-fluoro-4,5-dihydroxy-phenyl)-morpholine-4-yl-methanone (example b) and 2-chloro-4'-methoxy-diphenyldichlorosilane (example 98A). White powder.

MS: m/e=424,3 ([M+H]+).

Example 102

Obtain (6-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-[4-(4-fluoro-phenyl)-piperazine-1-yl]-methanone

a) Obtaining (4,5-bis-benzyloxy-2-fluoro-phenyl)-[4-(4-fluoro-phenyl)-piperazine-1-yl]-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example d on the basis of 4,5-bis-benzyloxy-2-fluoro-benzoic acid (example V) and 1-(4-forefeel)piperazine. Light yellow powder.

MS: m/e=514,6 ([M+H]+).

b) Receiving (2-fluoro-4,5-dihydroxy-phenyl)-[4-(4-fluoro-phenyl)-piperazine-1-yl]-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example b on the basis of (4,5-bis-benzyloxy-2-fluoro-phenyl)-[4-(4-fluoro-phenyl)-piperazine-1-yl]-methanone (example 102A). White powder.

MS: m/e=335,2 ([M+H]+).

C) Getting (6-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-[4-(4-fluoro-phenyl)-piperazine-1-yl]-methanone

At asanee in the title compound was obtained in accordance with the General method described in example 108b, on the basis of (2-fluoro-4,5-dihydroxy-phenyl)-[4-(4-fluoro-phenyl)-piperazine-1-yl]-methanone (example b) and dichlorodiphenylmethane. Light brown powder.

MS: m/e=499,2 ([M+H]+).

Example 103

Obtaining [6-fluoro-2-(4-fluoro-phenyl)-2-phenyl-benzo[1,3]dioxol-5-yl]-[4-(4-fluoro-phenyl)-piperazine-1-yl]-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 108b, on the basis of (2-fluoro-4,5-dihydroxy-phenyl)-[4-(4-fluoro-phenyl)-piperazine-1-yl]-methanone (example b) and 4-fortifiediron (example 97A). Grey powder.

MS: m/e=from 517.2 ([M+H]+).

Example 104

Obtaining [2-(2-chloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-[4-(4-fluoro-phenyl)-piperazine-1-yl]-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 108b, on the basis of (2-fluoro-4,5-dihydroxy-phenyl)-[4-(4-fluoro-phenyl)-piperazine-1-yl]-methanone (example b) and 2-chloro-4'-methoxy-diphenyldichlorosilane (example 98A). Orange powder.

MS: m/e=563,2 ([M]+).

Example 105

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

a) Obtaining 2,4-dichloro-4'-methoxy-diphenyldichlorosilane

Specified in the header of the giving was obtained in accordance with the General method described in example b based on 2,4-dichlorobenzotrifluoride and anisole. Red oil.

NMR (300 MHz, CDCl3) ppm: by 8.22 (d, 1H), 7,43-7,29 (m, 4H), 6,85 (d, 2H), of 3.73 (s, 3H).

b) Receiving [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 108b, on the basis of (2-fluoro-4,5-dihydroxy-phenyl)-piperidine-1-yl-methanone (example d) and 2,4-dichloro-4'-methoxy-diphenyldichlorosilane (example 105A). Orange oil.

MS: m/e=502,3 ([M+H]+).

Example 106

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 108b, on the basis of (2-fluoro-4,5-dihydroxy-phenyl)-morpholine-4-yl-methanone (example b) and 2,4-dichloro-4'-methoxy-diphenyldichlorosilane (example 105A). A yellow oil.

MS: m/e=504,3 ([M+H]+).

Example 107

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-[4-(4-fluoro-phenyl)-piperazine-1-yl]-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 108b, on the basis of (2-fluoro-4,5-dihydroxy-phenyl)-[4-(4-fluoro-phenyl)-piperazine-1-yl]-methanone (prima is b) and 2,4-dichloro-4'-methoxy-diphenyldichlorosilane (example 105A). Brown butter.

MS: m/e=597,2 ([M]+).

Example 108

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

a) Obtaining 4-bromo-5-fluoro-benzene-1,2-diol

To a cooled to -78°With the solution of 4-forevertron (5.0 g, 32 mmol) in dichloromethane (106 ml) was slowly added a solution of tribromide boron in dichloromethane (1 M, 96 ml, 96 mmol, 3.0 EQ.). The reaction mixture was heated to 20°and was stirred overnight. The reaction mixture was poured into ice water, extracted with ethyl acetate (three times). The organic fractions were combined, washed with aqueous sodium bicarbonate solution, dried over sodium sulfate and was filtered. Volatile components were removed in vacuum. The obtained brown solid residue was dissolved in chloroform (50 ml) and dichloromethane (10 ml). To the resulting solution was slowly added a solution of bromine in carbon tetrachloride (5 ml). After three hours, the volatile components were removed in vacuum. After purification by the method of accelerated chromatography indicated in the title compound was obtained as a brown powder (6,51 g, 98%).

MS: m/e=207,9 ([M+H]+).

b) Obtain 2,4-dichloro-4'-fluoro-diphenyldichlorosilane

To a cooled to 0°suspension trichloride aluminum (2,02 g, 15 mmol, 3.0 EQ.) in 1,2-dichloroethane (7 ml) was slowly added 2,4-dichlo benzotrifluoride (1.1 g, 5 mmol), and then florabunda (0,483 g, 5 mmol, 1.0 EQ). The reaction mixture was stirred for 5 hours at a temperature of 0-5°C, then poured into ice, extracted with dichloromethane. The organic fractions were combined, washed with saturated aqueous sodium chloride, dried over sodium sulfate and was filtered. Volatile components were removed in vacuum, obtaining mentioned in the title compound as a yellow oil (1.63 g, quantitative yield).

MS: m/e=325,0 ([M+H]+.

C) Obtain 5-bromo-2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxole

A mixture of 4-bromo-5-fluoro-benzene-1,2-diol (to 6.43 g, and 31.1 mmol) and 2,4-dichloro-4'-fluoro-chlorodiphenylmethane (10,07 g, 31,1 mmol, 1.0 EQ.) was heated with stirring at a temperature of 180°C for 20 minutes the Reaction mixture was cooled to 20°C, was diluted with dichloromethane and adsorbing on silica gel. After purification by the method of accelerated chromatography the product was obtained as a pale yellow powder (9,98 g, 70%).

MS: m/e=457,9 ([M+H]+).

g) Receiving [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

To a cooled to -78°With a solution of 5-bromo-2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxole (16.5 g, 36,0 mmol) in diethyl ether (250 ml) was slowly added a solution of n-utility in hexane (1.6 M, 23 ml, 36,0 mmol, 1.0 EQ.). The reaction mixture vydergivali a temperature of -78° C for 1 h, then was added solid carbon dioxide (approximately 50 g). The reaction mixture was left to warm to 20°C. After 16 h at 20°the reaction mixture was transferred into a mixture of water (150 ml), ethyl acetate (1.5 l) and hydrochloric acid (1 N., 150 ml). The aqueous fraction was extracted with ethyl acetate and the combined organic fractions were washed with water. Volatile components were removed in vacuum. The residue was purified by the method of accelerated chromatography, getting mentioned in the title compound as a pale yellow powder (of 10.73 g, 69%).

MS: m/e=422,3 ([M-H]-).

d) [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

To a solution of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (380 mg, 0,898 mmol) in N,N-dimethylformamide (7 ml) was added carbonyldiimidazole (189 mg, 1,17 mmol, 1.3 EQ.). The reaction mixture was stirred for 16 h at 20°C. was Added morpholine (196 mg, 2,24 mmol, 2.5 equiv.) the reaction mixture was stirred at 90°C for 8 h, the Reaction mixture was transferred into a mixture of 1 N. hydrochloric acid and ethyl acetate. The organic fraction was washed with a saturated solution of sodium chloride, water, volatile components were removed in vacuum. After purification by the method of accelerated chromatography the product was obtained as a white powder (367 mg, 83%).

MS: m/e=493,43 ([M+H]+).

Example 110

Obtain (6-methyl-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanone

a) Obtaining 4-bromo-5-methylpyrimidine

To a solution of homoveratric (to 136.4 g, 1.1 mol) in chloroform (1.2 l) and dichloromethane (300 ml) was slowly added a solution of bromine (66 ml, 1.28 mol, 1.2 EQ.) in carbon tetrachloride (250 ml). After 5 h the reaction mixture was neutralized to pH 7 by addition of an aqueous sodium hydroxide solution and the aqueous fraction was extracted with chloroform. The organic fractions were combined, dried over sodium sulfate and the volatile components were removed in vacuum, obtaining the product as a light brown powder, tPL: 92-98°C.

b) Obtain 5-bromo-6-methyl-2,2-diphenyl-benzo[1,3]dioxole

Specified in the title compound was obtained in accordance with the General procedure described in example 108b, from 4-bromo-5-methylpyrimidine and diphenyldichlorosilane. White powder.

MS: m/e=368,0 ([M+H+]).

C) Obtaining the lithium salt of 6-methyl-2,2-diphenyl-1,3-benzodioxol-5-carboxylic acid

To a cooled to -70°With a solution of 5-bromo-6-methyl-2,2-diphenyl-benzo[1,3]dioxole (example road 110, to 91.8 g, 250 mmol) in tetrahydrofuran (140 ml) was slowly added a solution of n-utility in hexane (170 ml, 1.6 M, 1.1 EQ.) and tetrahydrofuran (100 ml). After 15 minutes, was added an excess of solid carbon dioxide. The reaction to shift the ü was left to warm to room temperature. The precipitation was filtered and dried in vacuum, obtaining mentioned in the title compound as a white powder (79,4 g, 77%).

MS: m/e=345,2 ([M+2Li]).

g) Getting (6-methyl-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanone

To a solution of the lithium salt of 6-methyl-2,2-diphenyl-1,3-benzodioxol-5-carboxylic acid (101,5 mg, 0.3 mmol) in N,N-dimethylformamide (3 ml) was added hexafluorophosphate N,N,N',N'-tetramethyl-O-(1H-benzotriazol-1-yl)-Urania (114 mg, 0.3 mmol, 1.0 EQ.). The reaction mixture was stirred at 20°C for 1 h was Added piperidine (26 mg, 0.3 mmol, 1.0 EQ.), and the reaction mixture was stirred at 20°C for 20 hours, the Reaction mixture was transferred into a mixture of ethyl acetate - water. The aqueous fraction was extracted with ethyl acetate. The organic fractions were combined, washed with water, saturated sodium chloride solution and dried over sodium sulfate, filtered and evaporated. After purification by the method of accelerated chromatography indicated in the title compound was obtained as a pale yellow powder (73 mg, 61%).

MS: m/e=400,2.

Example 111

Obtaining [6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

a) Obtaining 4,4'-debtor-diphenyldichlorosilane

Specified in the title compound was obtained in accordance with the General procedure described in example 88 g, based on the C 4,4'-differentfree. A yellow oil.

MS: m/e=272 ([M-H]+).

b) Receiving [6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 108b, on the basis of (3,4-dihydroxy-phenyl)-morpholine-4-yl-methanone (example b) and 4,4'-debtor-diphenyldichlorosilane (example 111a). The white foam.

MS: m/e=442,3 ([M+H]+).

Example 112

Obtain (6-bromo-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanone

a) Obtaining 6-bromo-2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid

To a solution of 5-bromo-6-methyl-2,2-diphenyl-benzo[1,3]dioxole (5.20 g, 14.1 mmol, example road 110) in pyridine (52 ml) and water (26 ml) at room temperature was added potassium permanganate (of 6.71 g, 42,5 mmol, 3.0 EQ.). After three hours the reaction mixture was transferred into a mixture of water - hydrochloric acid (1 BC). The aqueous fraction was extracted with ethyl acetate. After evaporation the residue was adsorbing on silica gel. After purification by the method of accelerated chromatography indicated in the title compound was obtained as a colourless powder (4,656 g, 83%).

MS: m/e=395,0 ([M-H]-).

b) Getting (6-bromo-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example d on the basis of 6-br is mo-2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (example a) and piperidine. White powder.

MS: m/e=464,1 ([M+H]+).

Example 113

Obtain (+)-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained by the method of preparative chiral HPLC (ChiralPak AD) of racemic [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone (example d). White powder.

MS: m/e=493,3 ([M+H]+).

Example 114

Obtaining (-)-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained by the method of preparative chiral HPLC (ChiralPak AD) of racemic [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone (example d). White powder.

MS: m/e=493,3 ([M+H]+).

Example 115

Obtaining [2-(2,4-dichloro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 108b, from 2,4-dichloro-4'-fluoro-diphenyldichlorosilane (example b) and (3,4-dihydroxy-phenyl)-morpholine-4-yl-methanone (example b). Light yellow resin.

MS: m/e=474,1 ([M+H]+).

Example 116

Obtaining [2-(2,4-dichloro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 108b, from 2,4-dichloro-4'-fluoro-diphenyldichlorosilane (example b) and (3,4-dihydroxy-phenyl)-piperidine-4-yl-methanone. Light yellow resin.

MS: m/e=472,2 ([M+H]+).

Example 117

Obtain (6-chloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanone

a) Getting (6-chloro-benzo[1,3]dioxol-5-yl)-piperidine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example V on the basis of 6-chloro-1,3-benzodioxol-5-carboxylic acid and piperidine. Colorless powder, tPL: 138-139°C.

MS: m/e=267,9 ([M+H]+).

b) Receiving (2-chloro-4,5-dihydroxy-phenyl)-piperidine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example b on the basis of (6-chloro-benzo[1,3]dioxol-5-yl)-piperidine-4-yl-methanone (example 117a). Light gray powder.

MS: m/e=256,1 ([M+H]+).

C) Getting (6-chloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 108b based on α,α-diphenyldichlorosilane and (2-chloro-4,5-dihydroxy-phenyl)-piperidine-4-yl-methanone (example b). Colorless then the shock.

MS: m/e=418,1 ([M]+).

Example 118

Obtain (6-chloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 108b based on α,α-diphenyldichlorosilane and (2-chloro-4,5-dihydroxy-phenyl)-morpholine-4-yl-methanone (example b). White powder.

MS: m/e=422,0 ([M+H]+).

Example 119

Getting ethyl-methyl-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

To a solution of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G, 220 mg; 0.52 mmol; 1 EQ.) in N,N-dimethylformamide (5 ml) was added carbonyldiimidazole (110 mg; of 0.68 mmol; 1.3 EQ.), and the reaction mixture was stirred for 2 h at 20°C. was Added a solution of ethyl-methylamine in N,N-dimethylformamide (1 M, 1 ml; 1.3 mmol; 2.5 EQ.), and the reaction mixture was stirred at 20°C for 4 days. After purification by the method of preparative HPLC (YMC pro C18) specified in the title compound was obtained in the form of a 10 mm solution in DMSO.

MS: m/e=464,2 ([M]+).

Example 120

Obtaining methyl-propyl-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

Specified in the header of the connection would is obtained in accordance with the General method described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and methylpropylamine.

MS: m/e=478,2 ([M]+).

Example 121

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo [1,3]dioxol-5-yl]-(2-methyl-pyrrolidin-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and 2-methyl-pyrrolidine.

MS: m/e=490,2 ([M]+).

Example 122

Getting azepin-1-ylamide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and 1-aminoguanidine.

MS: m/e=519,3 ([M]+).

Example 123

Getting azetidin-1-yl-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carbon is howling acid (example 108G) and azetidine.

MS: m/e=462,2 ([M]+).

Example 124

Getting azepin-1-yl-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and azacycloheptane.

MS: m/e=504,2 ([M]+).

Example 125

Receiving (2,2-dimethyl-1-methylcarbamoyl-propyl)-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and L-tert-leucine-N-methylamide.

MS: m/e=549,4 ([M]+).

Example 126

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(2-8-methoxymethyl-pyrrolidin-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and 2-S-methoxymethyl-pyrrolidine.

MS: m/e=520,4 ([M]+).

Example 127

Obtaining [2(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(2-R-hydroxymethyl-pyrrolidin-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and 2-R-hydroxymethyl-pyrrolidine.

MS: m/e=506,2 ([M]+).

Example 128

Getting dimethylamide 1-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carbonyl]-pyrrolidin-2-R-carboxylic acid

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and 2-R-carboxylic acid of dimethylaminopyridine.

MS: m/e=547,3 ([M]+).

Example 129

Getting cyclobutylamine 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and cyclobutylamine.

MS: m/e=476,3 ([M]+).

Example 130

Getting morpholine-4-ylamide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and N-aminomorpholine.

MS: m/e=507,2 ([M]+).

Example 131

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(2,3,5,6-tetrahydro-[1,2']bipyridinyl-4-yl)-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and 1-(2-pyrazinyl)-piperazine.

MS: m/e=569,3 ([M]+).

Example 132

Getting amide 1-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carbonyl]-pyrrolidin-2-S-carboxylic acid

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and the amide pyrrolidin-2-S-carboxylic acid.

MS: m/e=519,3 ([M]+).

Example 133

Obtain tert-butoxy-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

Specified in the header with the Association was obtained in accordance with the General method described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and tert-butoxy-amine.

MS: m/e=494,2 ([M]+).

Example 134

Getting cyclopentylamine 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and cyclopentylamine.

MS: m/e=490,3 ([M]+).

Example 135

Receiving (tetrahydro-furan-2-ylmethyl)-amide-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and (tetrahydro-furan-2-ylmethyl)-amine.

MS: m/e=506,2 ([M]+).

Example 136

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-thiomorpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-FPO is-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and thiomorpholine.

MS: m/e=508,2 ([M]+).

Example 137

Getting Isopropylamine 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and Isopropylamine.

MS: m/e=464,2 ([M]+).

Example 138

Getting pyrrolidin-1-ylamide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and pyrrolidinone.

MS:M/e=491,3 ([M]+).

Example 139

Getting methoxy-methyl-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and methoxy-methyl-amine.

MS: m/e=466,2 ([M]+).

Example 140

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-dryer is l)-benzo[1,3]dioxol-5-yl]-(3-R-hydroxy-pyrrolidin-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and 3-R-hydroxy-pyrrolidine.

MS: m/e=492,2 ([M]+).

Example 141

Obtaining bis-cyclopropylmethyl-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and bis-cyclopropylmethyl-amine.

MS: m/e=530,2 ([M]+).

Example 142

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-fluoro-piperidine-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and 4-fluoro-piperidine.

MS: m/e=530,2 ([M]+).

Example 143

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(1,4-dioxa-8-Aza-Spiro[4.5]Dec-8-yl)-methanone

Specified in reception is e compound was obtained in accordance with the General method described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and 1,4-dioxa-8 azaspiro(4,5)decane.

MS: m/e=548,3 ([M]+).

Example 144

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-hydroxymethyl-piperidine-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and 4-hydroxymethyl-piperidine.

MS: m/e=520,3 ([M]+).

Example 145

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-hydroxy-4-methyl-piperidine-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and 4-hydroxy-4-methyl-piperidine.

MS: m/e=520,3 ([M]+).

Example 146

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-pyrrolidin-1-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and pyrrolidine.

MS: m/e=476,1 ([M]+).

Example 147

Obtain N-{1-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carbonyl]-pyrrolidin-3-8-yl}-ndimethylacetamide

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and 3-S-acetaminophenodeine.

MS: m/e=533,2 ([M]+).

Example 148

Getting cycloheptylamine 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and cycloheptylamine.

MS: m/e=518,3 ([M]+).

Example 149

Obtaining N'-pyridin-2-yl-hydrazide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and 2-hydrazinopyridazine.

MS: m/e=514,3 ([M]+).

Example 150

Receiving (2-5-methoxymethyl-p is Raiden-1-yl)-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and 2-S-methoxymethyl-pyrrolidin-1-amine.

MS: m/e=534,2 ([M]+).

Example 151

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(1,1-dioxo-thiomorpholine-4-yl)-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and 1,1-dioxo-1-thiomorpholine.

MS: m/e=540,4 ([M]+).

Example 152

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(3-hydroxy-8-Aza-bicyclo[3,2,1]Oct-8-yl)-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and nortropine.

MS: m/e=532,2 ([M]+).

Example 153

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo [1,3]dioxol-5-yl]-(2-R-methoxymethyl-pyrrolidin-1-yl)-methanone

Specified in the connection was obtained in accordance with the General method described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and 2-R-methoxymethyl-pyrrolidine.

MS: m/e=520,2 ([M]+).

Example 154

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(3-5-hydroxy-pyrrolidin-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and 3-S-hydroxy-pyrrolidin.

MS: m/e=492,2 ([M]+).

Example 155

Obtain N-{1-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carbonyl]-pyrrolidin-3R-yl}-ndimethylacetamide

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and 3-R-acetamido-pyrrolidine.

MS: m/e=533,3 ([M]+).

Example 156

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(2-8-hydroxymethyl-pyrrolidin-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example 119, on the basis of [2-(2,4-dichloro-phenyl)6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and 2-S-hydroxymethyl-pyrrolidine.

MS: m/e=506,2 ([M]+).

Example 157

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-meantion

A mixture of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone (example d, 79 mg, 0.16 mmol) and reagent Lawesson (Lawesson) (33 mg, 0.08 mmol) in benzene (1 ml) was boiled under reflux for 4 hours, the Reaction mixture was evaporated in vacuum. After purification by the method of accelerated chromatography the product was obtained as a yellow oil (75 mg, 92%).

MS: m/e=508,0 ([M]+).

Example 158

Obtaining [2-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

a) Obtaining 2,4,4'-trichlorophenylacetic

Specified in the title compound was obtained in accordance with the General procedure described in example b on the basis of 2,4-dichloro-benzotrifluoride and chlorobenzene. Brown butter.

MS: m/e=339,9 ([M]+).

b) Obtain 5-bromo-2-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxole

Specified in the title compound was obtained in accordance with the General procedure described in example 108b, from 4-bromo-5-fluoro-benzene-1,2-diol (example 108A) and 2,4,4'-trichlorovinylsilane (example a). White powder.

MS: m/e=473,9 ([M]+).

C) Obtaining 2-(4-chloro-phenyl-2-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General procedure described in example 108G, starting from 5-bromo-2-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxole (example b). Orange powder.

MS: m/e=437,0 ([M-H]-).

g) Receiving [2-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example d, based on 2-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid (example V) and research. Orange powder.

MS: m/e=508,3 ([M+H]+).

Example 159

Getting 6-(morpholine-4-carbonyl)-2,2-diphenyl-benzo[1,3]dioxol-5-carbonitrile

a) Getting (6-bromo-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example d on the basis of 6-bromo-2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid (example 110) and the research. White powder.

MS: m/e=466,2 ([M+H]+).

b) Obtain 6-(morpholine-4-carbonyl)-2,2-diphenyl-benzo[1,3]dioxol-5-carbonitrile

A mixture of (6-bromo-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanone, (204 mg, 0,437 mmol) and copper cyanide (102 mg, 1,139 mmol, 2.6 EQ.) in N-methyl-pyrrolidinone (3 ml) was heated to a temperature of 190° C for 16 h, the Reaction mixture was transferred into a mixture of water - ethyl acetate. The organic fraction was washed with a saturated solution of sodium chloride and evaporated in vacuum. After purification by the method of accelerated chromatography the product was obtained as a colourless powder (4,656 g, 83%).

MS: m/e=413,1 ([M+H]+).

Example 160

Obtaining [2-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

Specified in the title compound was obtained in accordance with the General procedure described in example d, based on 2-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid (example V) and piperidine. White powder.

MS: m/e=506,0 ([M+H]+).

Example 161

Obtaining [2-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-pyrrolidin-1-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example d of 2-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid (example V) and pyrrolidine. Colorless powder.

MS: m/e=491,9 ([M+H]+).

Example 162

Getting [2,2-bis-(2,4-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

a) Obtaining 2,2',4,4'-tetrafluorodichloroethane

To 1,3-diferently (8 g, 70,12 IMO the ü) under stirring was added trichloride aluminum (5.32 g, and 39.9 mmol). The mixture was cooled to approximately 10°and was added dropwise tetrachloride carbon (14,5 ml) for 1 h, the Mixture was stirred for 3.5 h at 30°C, was diluted with dichloromethane and poured into ice. Fractions were separated, the organic fraction was dried over magnesium sulfate and evaporated to obtain specified in the title compound as a pale brown powder, which was used in the next stage without additional purification.

MS: m/e 273,0 ([M-Cl]-).

b) obtaining a [2,2-bis-(2,4-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example 108b of 2,2',4,4'-tetrafluorodichloroethane and (3,4-dihydroxy-phenyl)-morpholine-4-yl-methanone (example b). Light brown resin.

MS: m/e=460,1 ([M+H]+).

Example 163

Getting [2,2-bis-(2,4-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example 108b of 2,2',4,4'-tetrafluorodichloroethane (example a) and (3,4-dihydroxy-phenyl)-piperidine-4-yl-methanone. Yellow foam.

MS: m/e=458,3 ([M+H]+).

Example 164

Obtaining [6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-pyrrolidin-1-yl-methanone

a) Receiving 5-bromo-6-f the PR-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxole

Specified in the title compound was obtained in accordance with the General method of example 108b, from 4-bromo-5-fluoro-benzene-1,2-diol (example 108A) and 4,4'-diftormetilirovaniya (example 111a). A colorless oil.

MS: m/e=407,9 ([M]+).

b) Receiving [6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-pyrrolidin-1-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example b of 5-bromo-6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxole (example a) and 1-pyrrolidin-carbonylchloride. Light yellow oil.

MS: m/e=426,3 ([M+H]+).

Example 165

Obtaining [6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example b of 5-bromo-6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxole (example a) and 1-piperidine-carbonylchloride. A yellow oil.

MS: m/e=440,3 ([M+H]+).

Example 166

Getting [2,2-bis-(4-bromo-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

a) Receiving 5-bromo-6-fluoro-2,2-diphenyl-benzo[1,3]dioxole

Specified in the title compound was obtained in accordance with the General method of example 108b, from 4-bromo-5-fluoro-benzene-1,2-diol (example 108A) and diphenyldichlorosilane. Colorless powder.

MS: m/e=370,0 ([M+H+]).

b) Getting (6-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanone

To a cooled (-78° (C) to a solution of 5-bromo-6-fluoro-2,2-diphenyl-benzo[1,3]dioxole (17,59 g, with 47.4 mmol) in diethyl ether (300 ml) was slowly added a solution of n-utility in hexane (1.6 M, 30 ml, 48 mmol, 1.0 equiv.). The reaction mixture was stirred 1 h at -78°and was added 4-morpholinylcarbonyl (8.5 g, 56,9 mmol, 1.2 equiv.). The reaction mixture was heated to 20°and was poured into aqueous sodium bicarbonate solution. The aqueous fraction was extracted with ethyl acetate. The organic fractions were combined and washed with a saturated solution of sodium chloride. Volatile impurities were removed in vacuum. The accelerated cleanup chromatography resulted in the receipt specified in the connection header (13,0 g, 68%) as a pale yellow powder.

MS: m/e=406,2 ([M+H]+).

C) Getting (2-fluoro-4,5-dihydroxy-phenyl)-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example b of (6-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanone. Light brown powder.

MS: m/e=442,2 ([M+H]+).

g) Obtaining 4,4'-dibromodichloromethane

Specified in the title compound was obtained in accordance with the General method of example b of 4-bromobenzonitrile and bromine benzol. Light yellow semi-solid powder.

MS: m/e=392,0 ([M+H]+.

d) [2,2'-bis-(4-bromo-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example 108b (2-fluoro-4,5-dihydroxy-phenyl)-morpholine-4-yl-methanone (example V) and 4,4'-dibromodichloromethane (example g). Light yellow powder.

MS: m/e=364,1 ([M+H]+).

Example 167

Getting 4-[2,2-bis-(4-cyano-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carbonyl]-research

A mixture of [2,2'-bis-(4-bromo-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone (example d, 400 mg, 0.71 mmol, 1.0 equiv.), of copper cyanide (381 mg, 4.26 deaths mmol, 6,0 equiv.), Tris(dibenzylideneacetone)diplegia (32,5 mg, 0.035 mmol, of 0.05 equiv.), cyanide of tetraethylammonium (111 mg, 0.71 mmol, 1.0 equiv.) and 1,1'-bis(diphenylphosphino)ferrocene (78,7 mg, 0,142 mmol, 0.2 equiv.) saturated with nitrogen. Added degassed dioxane (10 ml)and the reaction mixture was heated at the boil under reflux for 4 hours, the Reaction mixture was diluted with ethyl acetate, filtered and washed with an aqueous solution of sodium bicarbonate, a saturated solution of sodium chloride and water. Volatile impurities were removed in vacuum. The accelerated cleanup chromatography resulted in the receipt specified in the title compound (141 mg, 44%) as a pale yellow semi-solid powder.

MS: m/e=456,1 ([M+H+]).

Example 16

Getting 4-[2-(4-bromo-phenyl)-5-fluoro-6-(morpholine-4-carbonyl)-benzo[1,3]dioxol-2-yl]-benzonitrile

Specified in the title compound was obtained in accordance with the General method of example 167, as a by-product. Light yellow powder.

MS: m/e=509,0 ([M+H+]).

Example 169

Getting [2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example 108b of 2,2',4,4'-tetrafluorodichloroethane (example a) and (2-fluoro-4,5-dihydroxy-phenyl)-morpholine-4-yl-methanone (example b). Light brown resin.

MS: m/e=478,1 ([M+H]+).

Example 170

Getting [2,2-bis-(4-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

a) Obtaining dichlorobis(4-chlorophenyl)methane

Specified in the title compound was obtained in accordance with the General method of example g of 4,4'-dichlorobenzophenone and used without additional purification. Yellow powder.

MS: m/e=304,0, 306,0 ([M]+).

b) obtaining a [2,2-bis-(4-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example 108b of dichlorobis(4-chlorophenyl)methane and 2-fluoro-4,5-Digi the Roxy-phenyl)-morpholine-4-yl-methanone (example V). Beige foam.

MS: m/e=474,0, 476,0 ([M]+).

Example 171

Obtaining [6-chloro-2,2-bis-(2,4-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example 108b of 2,2',4,4'-tetrafluorodichloroethane (example a) and (2-chloro-4,5-dihydroxy-phenyl)-morpholine-4-yl-methanone (example b). Light yellow resin.

MS: m/e=494,1 ([M+H]+).

Example 172

Obtaining [2-(2-chloro-4-fluoro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

a) 2-chloro-1-[dichloro-(4-fluoro-phenyl)-methyl]-4-fluoro-benzene

(2-Chloro-4-fluoro-phenyl)-(4-fluoro-phenyl)-methanon (0.25 g, 0,99 mmol) and pentachloride phosphorus (0.21 g, 1.01 mmol) were mixed in an argon atmosphere and was heated for 2 h at 150°C. the Mixture was cooled to room temperature, diluted with dichloromethane and poured into ice. Fractions were separated, the organic fraction was dried over magnesium sulfate and evaporated to obtain specified in the title compounds as a pale yellow oil (0.2 g), containing approximately 50% of the desired product according to NMR data, together with the reference compound (35%) and monochloropropane connection (15%). The mixture was used without further purification.

b) Receiving [2-(2-chloro-4-fluoro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-Il-IU is the anon

Specified in the title compound was obtained in accordance with the General method of example 108b, from 2-chloro-1-[dichloro-(4-fluoro-phenyl)-methyl]-4-fluoro-benzene (example a) and (3,4-dihydroxy-phenyl)-piperidine-4-yl-methanone. Light brown resin.

MS: m/e=456,1 ([M+H]+).

Example 173

Obtaining [6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

a) Obtaining bis-(2-fluoro-phenyl)-methanone

To a stirred suspension of 2-fermentable acid (280 mg, 2 mmol), Cs2CO3(1.63 g, 5 mmol) and tetrakis(triphenylphosphine)palladium(0) (40 mg, 0.02 mmol) in toluene (35 ml) was added dropwise in a nitrogen atmosphere 2-perbenzoate (634 mg, 4 mmol). The suspension was heated at 100°C for 16 h, cooled to room temperature and was divided between ethyl acetate and water. The organic fraction was washed with an aqueous solution of potassium bicarbonate, saturated sodium chloride solution, dried over sodium sulfate, filtered and evaporated. The accelerated cleanup chromatography resulted in the receipt specified in the title compound (210 mg, 46%). Colorless liquid.

MS: m/e=218,1 ([M+).

b) Obtaining bis-(2-forfinal)dichloromethane

Specified in the title compound was obtained in accordance with the General method of example a of bis-(2-fluoro-phenyl)-methanone (example a) and use what has been in use without additional purification. Brown powder.

C) Obtaining [6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example 108b (2-fluoro-4,5-dihydroxy-phenyl)-morpholine-1-yl-methanone (example b) and bis-(2-forfinal)dichloromethane (example b). Light brown amorphous powder.

MS: m/e=442,3 ([M+H]+).

Example 174

Getting [2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

a) Obtaining 2,2',4,4'-tetrachloro-dichlorodiphenylmethane

Specified in the title compound was obtained in accordance with the General method of example 207a of 2,4-dichlorobenzene and were used without additional purification. White crystals.

tPL: 139-142°C; MS: m/e=373,9, 375,9 ([M]+).

b) obtaining a [2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example 108b of 2,2',4,4'-tetrachloro-dichlorodiphenylmethane and 2-fluoro-4,5-dihydroxy-phenyl)-morpholine-4-yl-methanone (example V). The white foam.

MS: m/e=541,9, 543,9 ([M]+).

Example 175

Getting 4-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-research

Specified in the title compound was obtained in ACCOR is availa able scientific C with the General method of example 108b of 2,2',4,4'-tetrafluorodichloroethane (example a) and 4-fluoro-5-(morpholine-1-sulfonyl)-benzene-1,2-diol (example b). Colorless foam.

MS: m/e=514,2 ([M+H]+).

Example 176

Getting 4-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-research

Specified in the title compound was obtained in accordance with the General method of example 108b of 2,4-dichloro-4'-fluoro-diphenyldichlorosilane and 4-fluoro-5-(morpholine-1-sulfonyl)-benzene-1,2-diol (example b). Colorless foam.

MS: m/e=528,1 ([M+H]+).

Example 177

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4,4-debtor-piperidine-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General method of example d of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and 4,4'-deformability. Yellow resin.

MS: m/e=526,1 ([M]+).

Example 178

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-trifluoromethyl-piperidine-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General method of example d of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) hydrochloride and 4-(trifluoromethyl)piperidine. The white foam.

MS: m/e=558,0 ([M]+).

Example 179

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-FPO is-phenyl)-benzo[1,3]dioxol-5-yl]-(3S-ethoxy-pyrrolidin-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General method of example d of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and 3S-ethoxy-pyrrolidine. A colorless oil.

MS: m/e=520,1 ([M]+).

Example 180

Obtaining (1R-phenyl-ethyl)-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General method of example d of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and (1R-phenyl-ethyl)-amine. A colorless oil.

MS: m/e=526,1 ([M]+).

Example 181

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(1-oxo-thiomorpholine-4-yl)-methanone

A solution of m-chloroperbenzoic acid (74 mg, 0.3 mmol) in dichloromethane (1.2 ml) was added to a cooled (-20° (C) a solution of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-thiomorpholine-4-yl-methanone (example 136) (153 mg, 0.3 mmol) in dichloromethane (1.7 ml). The reaction mixture was stirred at -20°C for 3 h, extinguished 5% aqueous sodium thiosulfate solution. The aqueous fraction was extracted with dichloromethane and the combined organic fractions were washed with 10% concrete is sodium bicarbonate and a saturated solution of sodium chloride, dried over sodium sulfate, was filtered and volatile impurities were removed in vacuum. The accelerated cleanup chromatography resulted in the receipt specified in the header of the product as a white foam (141 mg, 89%).

MS: m/e=524,1 ([M]+).

Example 182

Getting [2,2-bis-(2-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

a) Obtaining bis-(2-chlorophenyl)dichloromethane

A mixture of 2,2'-dichlorobenzophenone (502 mg, 2 mmol) and pentachloride phosphorus (833 mg, 4 mmol, 2.0 equiv.) was stirred for 28 h at 170°C. the Reaction mixture was cooled to room temperature, diluted with dichloromethane and washed with cold water. The organic fraction was dried over sodium sulfate, was filtered and volatile impurities were removed in vacuum, obtaining mentioned in the title compound (629 mg, quantitative yield) as an orange oil.

MS: m/e=306,0 ([M]+).

b) obtaining a [2,2-bis-(2-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

A mixture of bis-(2-chlorophenyl)dichloromethane (example 182, 258 mg, 0.84 mmol, 2.6 equiv.) and (2-fluoro-4,5-dihydroxy-phenyl)-morpholine-4-yl-methanone (example b, 72 mg, 0.32 mmol) was heated for 5 h at 150°s in a sealed glass tube. The accelerated cleanup chromatography resulted in the receipt specified in the title compound (6.8 mg, 4.5%) in the form of a colourless powder, tPL: 98°C.

MS: m/e=474,0 ([M+H]+).

Example 183

Obtaining [6-fluoro-2,2-bis-(4-trifluoromethyl-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

a) Obtaining bis-(4-trifluoromethyl-phenyl)-methanone

Specified in the title compound was obtained in accordance with the General method of example a of 4-trifluoromethyl-phenylboric acid and 4-trifluoromethyl-benzoyl chloride. White crystalline powder.

MS: m/e=318,1 ([M]+).

b) Obtaining bis-(4-trifluoromethyl-phenyl)dichloromethane

Specified in the title compound was obtained in accordance with the General method of example 87 g of bis-(4-trifluoromethyl-phenyl)-methanone (example 183a) and were used without additional purification. Brown powder.

C) Obtaining [6-fluoro-2,2-bis-(4-trifluoromethyl-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example 108b (2-fluoro-4,5-dihydroxy-phenyl)-morpholine-1-yl-methanone (example b) and bis-(4-trifluoromethyl-phenyl)dichloromethane (example b). Light brown amorphous powder.

MS: m/e=542,1 ([M+H]+).

Example 184

Obtaining [6-fluoro-2,2-bis-(3-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

a) Obtaining bis-(3-forfinal)dichloromethane

Specified in the title compound was obtained in the accordance with the General method of example g of bis-(3-fluoro-phenyl)-methanone and were used without additional purification. Brown powder.

b) Obtaining [[6-fluoro-2,2-bis-(3-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example 108b (2-fluoro-4,5-dihydroxy-phenyl)-morpholine-1-yl-methanone (example b) and bis-(3-forfinal)dichloromethane (example 184a). Colorless amorphous powder.

MS: m/e=442,1 ([M+H]+).

Example 185

Obtaining [2-(2-chloro-4-fluoro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example 108b, from 2-chloro-1-[dichloro-(4-fluoro-phenyl)-methyl]-4-fluoro-benzene (example a) and (3,4-dihydroxy-phenyl)-morpholine-4-yl-methanone (example b). Light brown resin.

MS: m/e=458,3 ([M+H]+).

Example 186

Getting [2,2-bis-(3,4-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example 108b of 1,1'-(dihlormetilen)bis[3,4-debtor-benzene and (3,4-dihydroxy-phenyl)-piperidine-4-yl-methanone. Light brown resin.

MS: m/e=458,2 ([M+H]+).

Example 187

Getting [2,2-bis-(3,4-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the header of the connection b is lo obtained in accordance with the General method of example 108b of 1,1'-(dihlormetilen)bis[3,4-debtor-benzene and (3,4-dihydroxy-phenyl)-morpholine-4-yl-methanone (example b). Colorless resin.

MS: m/e=460,2 ([M+H]+).

Example 188

Getting [2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(3-hydroxy-pyrrolidin-1-yl)-methanone

a) Receiving 5-bromo-2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxole

Specified in the title compound was obtained in accordance with the General method of example 108b of 2,2',4,4'-tetrachloro-dichlorodiphenylmethane (example a) and 4-bromo-5-fluoro-benzene-1,2-diol (example 108A). Colorless powder.

MS: m/e=507,9, 509,9 ([M]+).

b) Obtain 2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General method of example 108G of 5-bromo-2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxole. The white foam.

MS: m/e=471,0, 473,0 ([M-H]-).

C) obtaining a [2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(3-hydroxy-pyrrolidin-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid and 3-pyrrolidinone. Light yellow foam.

MS: m/e=541,9, 543,9 ([M]+).

Example 189

Getting [2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(4-hydroxy-piperidine-1-yl)-methanone

Specified in the title compound was obtained in the accordance with the General method of example g of 2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid and 4-hydroxy-piperidine. Light yellow foam.

MS: m/e=556,0, 558,0 ([M]+).

Example 190

Getting ethyl-methyl-amide 2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid and N-ethylmethylamine. The white foam.

MS: m/e=514,0, 516,0 ([M]+).

Example 191

Obtaining bis-(2-hydroxy-ethyl)-amide 2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid and diethanolamine. Light yellow foam.

MS: m/e=560, 0m, 562,0 ([M]+).

Example 192

Getting [2,2-bis-(4-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

a) Receiving 5-bromo-2,2-bis-(4-chloro-phenyl)-6-fluoro-benzo[1,3]dioxole

Specified in the title compound was obtained in accordance with the General method of example 108b of dichlorobis(4-chlorophenyl)methane (example a) and 4-bromo-5-fluoro-benzene-1,2-diol (example 108A). Colorless powder.

MS: m/e=437,9, 439,9, 441,9 ([M]+).

b) Obtain 2,2-bis-(4-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid is you

Specified in the title compound was obtained in accordance with the General method of example 108G of 5-bromo-2,2-bis-(4-chloro-phenyl)-6-fluoro-benzo[1,3]dioxole. Yellow powder.

MS: m/e=403,1, 405,1 ([M-H]-).

C) obtaining a [2,2-bis-(4-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(4-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid and piperidine. The white foam.

MS: m/e=472,1, 474,1 ([M]+).

Example 193

Getting [2,2-bis-(4-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-pyrrolidin-1-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(4-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid and pyrrolidine. The white foam.

MS: m/e=458,1, 460,1 ([M]+).

Example 194

Getting [2,2-bis-(2-chloro-4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

a) Obtaining 2,2'-dichloro-4,4 diftormetilirovaniya

Bis(2-chloro-4-forfinal)-methanon (1.6 g, to 5.57 mmol) and pentachloride phosphorus (1.4 g, 6,72 mmol) was heated for 5 h at 165°C in a sealed tube. The mixture was cooled to room temperature, diluted with dichloromethane and poured into ice. Fractions were separated, the organic fraction was dried over what Ulfat magnesium and evaporated to obtain specified in the title compound as a light brown oil (1,46 g), a mixture containing approximately 4:1 of the desired product to the original ketone (NMR), which was used without further purification.

NMR (300 MHz, CDCl3) cm: 8,39 (dd, 2H, J=4,5, and 6.6 Hz, product), 7,55 (dd, 0,5H, benzophenone), 7,17 (dd, 0,5H, J=4,5, 6,3 Hz, benzophenone), 7,10 (m, 4,5H, product, and benzophenone), 3,14 (m, 4H), 1.70 to of 1.40 (m, 6H).

b) obtaining a [2,2-bis-(2-chloro-4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example 108b of 2,2'-dichloro-4,4 diftormetilirovaniya and (3,4-dihydroxy-phenyl)-piperidine-4-yl-methanone. Light brown resin.

MS: m/e=490,1 ([M+H]+).

Example 195

Getting [2,2-bis-(3,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example 108b of 1,1'-(dihlormetilen)bis[3,4-debtor-benzene] and (2-fluoro-4,5-dihydroxy-phenyl)-morpholine-4-yl-methanone (example b). Colorless foam.

MS: m/e=478,3 ([M+H]+).

Example 196

Getting [2,2-bis-(2,5-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

a) Obtaining bis-(2,5-differenl)dichloromethane

Specified in the title compound was obtained in accordance with the General method of example 207a of the 2.5-diferente. Viscous light-coric Evoe oil.

MS: m/e=308,1 ([M]+).

b) obtaining a [2,2-bis-(2,5-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example 108b (2-fluoro-4,5-dihydroxy-phenyl)-morpholine-1-yl-methanone (example b) and bis-(2,5-differenl)dichloromethane (example I). Light brown amorphous powder.

MS: m/e=477,1 ([M]+).

Example 197

Getting [2,2-bis-(2-chloro-4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example 108b of 2,2'-dichloro-4,4'-diftormetilirovaniya (example a) and (3,4-dihydroxy-phenyl)-morpholine-4-yl-methanone (example b). Light yellow resin.

MS: m/e=492,2 ([M+H]+).

Example 198

Getting [2,2-bis-(2-chloro-4-fluoro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example 108b of 2,2'-dichloro-4,4 diftormetilirovaniya (example a) and (2-fluoro-4,5-dihydroxy-phenyl)-morpholine-4-yl-methanone (example b). Colorless foam.

MS: m/e=510,1 ([M+H]+).

Example 199

Obtaining [6-chloro-2,2-bis-(2-chloro-4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Pointed to by the e in the title compound was obtained in accordance with the General method of example 108b of 2,2'-dichloro-4,4 diftormetilirovaniya (example a) and (2-chloro-4,5-dihydroxy-phenyl)-morpholine-4-yl-methanone (example b). Light brown foam.

MS: m/e=526,1 ([M+H]+).

Example 200

Getting amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General method of example d of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example 108G) and ammonium hydroxide. The white foam.

MS: m/e=422 ([M]+).

Example 201

Getting [2,2-bis-(4-bromo-2-fluoro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

a) Obtaining 4,4'-dibromo-2,2'-debtor-benzophenone

Tetrakis(triphenylphosphine)palladium (0.15 g, 0.13 mmol) was dissolved in anisole (15 ml). Was added 1-bromo-3-fluoro-4-iadanza (2.0 g, 6.6 mmol), 4-bromo-2-ferbinteanu acid (1.45 g, 6.6 mmol) and potassium carbonate (2.7 g, to 19.9 mmol) together with 15 ml of anisole. The resulting mixture was stirred for 16 h at 80°under pressure of carbon monoxide of 10 bar. The reaction mixture was cooled, was added a mixture of toluene/water (120 ml, 1:1), the layers were separated and the aqueous fraction was extracted twice with toluene. The organic fraction was decanted, washed with a saturated solution of sodium chloride and the solvent was evaporated. Crystallization from hexane resulted in the receipt specified in the title compound as white crystals (1,17 g, 47%).

MS: me=375,9, 377,9 ([M+H]+).

b) Obtaining 4,4'-dibromo-2,2'-debtor-dichlorodiphenylmethane

A mixture of 4,4'-dibromo-2,2'-debtor-benzophenone (1.3 g, 3.5 mmol), phosphorus oxychloride (26 ml) and pentachloride phosphorus (4.4 g, 21 mmol) was stirred at boiling point for a period of 72 hours the Mixture was cooled and poured into a mixture of ice/water (200 ml). The product was extracted with dichloromethane. The organic fraction was decanted, dried over sodium sulfate and the solvent was removed in vacuum to obtain the product which was used without further purification. Brown butter.

MS: m/e=429,8, 431,8 ([M]+).

C) obtaining a [2,2-bis-(4-bromo-2-fluoro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example 108b of 4,4'-dibromo-2,2'-debtor-dichlorodiphenylmethane and 2-fluoro-4,5-dihydroxy-phenyl)-morpholine-4-yl-methanone (example V). A colorless oil.

MS: m/e=598,0, 600,0,602,0 ([M]+).

Example 202

Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(3,4-cis-dihydroxy-pyrrolidin-1-yl)-methanone

a) Obtaining [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(2,5-dihydro-pyrrol-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General method of example d of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[,3]dioxol-5-carboxylic acid (example 108G) and 3-pyrroline. A yellow oil.

MS: m/e=474([M]+).

b) Receiving [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(3,4-CIS-dihydroxy-pyrrolidin-1-yl)-methanon

To a solution of [2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(2,5-dihydro-pyrrol-1-yl)-methanone (70 mg, 0.15 mmol) in acetone (3,7 ml) and water (1.5 ml), was added monohydrate 4-methylmorpholine-4-oxide (23 mg, 0.16 mmol), osmium tetroxide (0,02 ml 0,0015 mmol) and the osmate dihydrate potassium (VI) (2.4 mg, 0,0065 mmol) and the reaction was stirred 24 h at 20°C. was Added pentahydrate sodium thiosulfate, the reaction mixture was stirred 30 min and poured into crushed ice. The aqueous fraction was extracted twice with ethyl acetate and the organic fractions were combined and washed with a saturated solution of sodium chloride, dried over sodium sulfate, was filtered and volatile impurities were removed in vacuum. The accelerated cleanup chromatography resulted in the receipt specified in the header of the product as a black oil (56 mg, 74%).

MS: m/e=508,1 ([M]+).

Example 203

Getting [2,2-bis-(2,3-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

a) Obtaining bis-(2,3-debtor-phenyl)-methanone

Specified in the title compound was obtained in accordance with the General method of example a of 2,3-diferentiovanny acid and 2,3-debtor-benzoyl chloride. Colorless to istoricheskii powder.

MS: m/e=254,1 ([M]+).

b) Obtaining bis-(2,3-differenl)dichloromethane

Specified in the title compound was obtained in accordance with the General method of example g of bis-(2,3-debtor-phenyl)-methanone (example a) and were used without additional purification. Brown powder.

C) obtaining a [2,2-bis-(2,3-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example 108b (2-fluoro-4,5-dihydroxy-phenyl)-morpholine-1-yl-methanone (example b) and bis-(2,3-differenl)dichloromethane (example b). Colorless amorphous powder.

MS: m/e=478,1 ([M+H]+).

Example 204

Obtaining [6-fluoro-2,2-bis-(4-triptoreline-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

a) Obtaining bis-(4-triptoreline-phenyl)-methanone

Specified in the title compound was obtained in accordance with the General method of example a of 4 triptoreline-basavaraj acid and 4-triptoreline-benzoyl chloride. Light brown powder.

MS: m/e=350 ([M]+).

b) Obtaining bis-(4-triptoreline-phenyl)dichloromethane

Specified in the title compound was obtained in accordance with the General method of example a of bis-(4-triptoreline-phenyl)-methanone (example a) in phosphorus oxychloride and was used without complement Inoi cleaning. Brown powder.

C) Obtaining [6-fluoro-2,2-bis-(4-triptoreline-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example 108b (2-fluoro-4,5-dihydroxy-phenyl)-morpholine-1-yl-methanone (example b) and bis-(4-trifluoromethyl-phenyl)dichloromethane (example b). Colorless amorphous powder.

MS: m/e=574,2 ([M+H]+).

Example 205

Getting [2,2-bis-(2-chloro-4,5-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example 108b of 1,1'-(dihlormetilen)bis[2-chloro-4,5-diferently and (3,4-dihydroxy-phenyl)-piperidine-4-yl-methanone. Colorless foam.

MS: m/e=526,1 ([M+H]+).

Example 206

Getting 4-[2,2-bis-(2-chloro-4-fluoro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-research

Specified in the title compound was obtained in accordance with the General method of example 108b of 2,2'-dichloro-4,4'-diftormetilirovaniya (example a) and 4-fluoro-5-(morpholine-1-sulfonyl)-benzene-1,2-diol (example b). Light brown powder.

MS: m/e=546,0 ([M+H]+).

Example 207

Getting [2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

a) Obtaining 2,2',4,4 tetrafluorodichloroethane

To a cooled (10° (C) a mixture of 1,3-diferente (50 g, 0,438 mol) and trichloride aluminum (33,3 g, 250 mmol, 0,57 equiv.) was slowly added carbon tetrachloride (91 ml). The reaction mixture was heated at 30°C for 4 h was Added ice-cold water. The aqueous fraction was extracted with dichloromethane. The organic fractions were combined and dried over sodium sulfate, was filtered, and volatile impurities were removed in vacuum, obtaining specified in the header of the connection of 60.3 g (89%) as a dark brown oil.

MS: m/e=273,2 ([M-Cl*]+).

b) Obtain 5-bromo-2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxole

Specified in the title compound was obtained in accordance with the General method of example 108b, from 4-bromo-5-fluoro-benzene-1,2-diol (example 108A) and [2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone (example 207a). Light yellow powder.

MS: m/e=444,0 ([M+H]+).

C) Obtaining 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General method of example 108G of 5-bromo-2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxole (example b). Yellow powder.

MS: m/e=407,0 ([M-H]-).

g) obtaining a [2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

Specified in the title compound was obtained in accordance with the General the method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid (example V) and piperidine. A yellow oil.

MS: m/e=476,1 ([M+H]+).

Example 208

Getting [2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(4-fluoro-piperidine-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid (example V) and 4-foreveryday. White powder.

MS: m/e=494,1 ([M+H]+).

Example 209

Getting [2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(4,4-debtor-piperidine-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid (example V) and 4,4-deformability. White powder.

MS: m/e=512,2 ([M+H]+).

Example 210

Getting [2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(4-trifluoromethyl-piperidine-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid (example V) and 4-(trifluoromethyl)piperidine. A yellow oil.

MS: m/e=544,2 ([M+H]+).

Example 211

Getting [2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(4-hydroxy-piperidine-1-yl)-meth is Nona

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid (example V) and 4-hydroxypiperidine. White powder.

MS: m/e=491,1 ([M+H]+).

Example 212

Getting [2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-thiomorpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid (example V) and 4-hydroxypiperidine. White powder.

MS: m/e=494,1 ([M+H]+).

Example 213

Getting [2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-pyrrolidin-1-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid (example V) and pyrrolidine. White powder.

MS: m/e=462,1 ([M+H]+).

Example 214

Getting [2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(3S-hydroxy-pyrrolidin-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]d is oxol-5-carboxylic acid (example V) and 3S-hydroxypyrrolidine. White powder.

MS: m/e=478,1 ([M+H]+).

Example 215

Getting [2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(2S-hydroxymethyl-pyrrolidin-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid (example V) and L-prolinol. White powder.

MS: m/e=492,2 ([M+H]+).

Example 216

Getting [2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(2S-methoxymethyl-pyrrolidin-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid (example V) and 2S-(methoxymethyl)pyrrolidine. Light yellow oil.

MS: m/e=506,1 ([M+H]+).

Example 217

Obtain (6-chloro-2,2-di-p-tolyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-metano

Specified in the title compound was obtained in accordance with the General method of example 233 g of bis(4-were)-meantion and (2-chloro-4,5-dihydroxy-phenyl)-morpholine-4-yl-methanone (example b). Light brown resin.

MS: m/e=450,2 ([M+H]+).

Example 218

Getting 4-[{6-chloro-10',11'-dihydro-Spiro[1,3-benzodioxole-2,5'-[5H]dibenzo[a,d]cyclohepten]-5-yl}carb is Neil]-research

a) Getting (6-chloro-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanone

To a mixture of 6-chloro-1,3-benzodioxol-5-carboxylic acid (0,49 g of 2.44 mmol) and hydroxybenzotriazole (66 mg, 0.49 mmol) in acetonitrile (20 ml) was added morpholine (of 0.53 ml, 6.1 mmol) and hydrochloride of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (0.52 g, 2.7 mmol). The orange solution was stirred 72 h at room temperature, diluted with ethyl acetate and poured into water. Fractions were separated, and the aqueous fraction was extracted with ethyl acetate. The organic fractions were combined and washed with a saturated solution of sodium chloride, dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified column chromatography on silica gel with obtaining specified in the title compound as a white powder (0,53 g, 80%), tPL155°C.

MS: m/e=270,2 ([M+H]+).

b) Obtain 2-chloro-4,5-dihydroxy-phenyl)-morpholine-4-yl-methanone

1 M solution of trichloride boron in dichloromethane (11 ml) was added dropwise to a chilled (ice bath) solution of (6-chloro-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanone (example 218a Centralnaya street) (1.98 g, 7,34 mmol) in dichloromethane (20 ml). The mixture was stirred over night at room temperature and was diluted with 1 M aqueous solution of potassium dihydrophosphate (10 ml). After stirring for 1 h, the layers were separated, and the aqueous fraction was AKST who was agarawala with ethyl acetate. The organic fractions were combined and washed with a saturated solution of sodium chloride, dried over magnesium sulfate and evaporated to obtain specified in the title compound as a brown foam (1,82 g, 96%), which was used without further purification.

MS: m/e=494,1 ([M+H]+).

C) Obtaining 4-[{6-chloro-10',11'-dihydro-Spiro[1,3-benzodioxole-2,5'-[5H]dibenzo[a,d]cyclohepten]-5-yl}carbonyl]-research

Specified in the title compound was obtained in accordance with the General method of example 233 g of 2,3,6,7-dibenzocycloheptadiene-1-thione and (2-chloro-4,5-dihydroxy-phenyl)-morpholine-4-yl-methanone (example b). Light brown powder.

MS: m/e=448,1 ([M+H]+).

Example 219

Obtaining [6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-fluoro-piperidine-1-yl)-methanone

a) Obtaining 6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General method of example 108G of 5-bromo-6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxole (example a). Light yellow foam.

MS: m/e=371,2 ([M-H]+).

b) Receiving [6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-fluoro-piperidine-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-CT is about acid (example a) and hydrochloride of 4-foreveryday. A yellow oil.

MS: m/e=458,2 ([M+H]+).

Example 220

Receiving (4,4-debtor-piperidine-1-yl)-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example a) and 4,4'-deformability. A yellow oil.

MS: m/e=476,1 ([M+H]+).

Example 221

Obtaining [6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-trifluoromethyl-piperidine-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example a) hydrochloride and 4-(trifluoromethyl)piperidine. A yellow oil.

MS: m/e=508,2 ([M+H]+).

Example 222

Obtaining [6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-thiomorpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example a) and thiomorpholine. Colorless foam.

MS: m/e=458,2 ([M+H]+).

Example 223

Obtain (3S-ethoxy-pyrrolidin-1-yl)-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example a) and 3S-ethoxypyrrolidine. A yellow oil.

MS: m/e=470,2 ([M+H]+).

Example 224

Obtaining [6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-[(S)-(2-methoxymethyl-pyrrolidin-1-yl)]-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example a) and 2S-methoxypiperidine. A yellow oil.

MS: m/e=470,2 ([M+H]+).

Example 225

Obtaining [6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-[(S)-2-hydroxymethyl-pyrrolidin-1-yl]-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example a) and L-prolinol. A yellow oil.

MS: m/e=456,1 ([M+H]+).

Example 226

Obtaining [6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-[(S)-3-hydroxy-pyrrolidin-1-yl]-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-CT is about acid (example a) and 3S-hydroxypyrrolidine. Yellow foam.

MS: m/e=442,1 ([M+H]+).

Example 227

Obtaining [6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-hydroxy-piperidine-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example a) 4-hydroxypiperidine. A yellow oil.

MS: m/e=456,1 ([M+H]+).

Example 228

Getting 4-[2,2-bis-(2-chloro-4,5-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-research

Specified in the title compound was obtained in accordance with the General method of example 108b of 1,1'-(dihlormetilen)bis[2-chloro-4,5-diferently and 4-fluoro-5-(morpholine-1-sulfonyl)-benzene-1,2-diol (example b). Colorless foam.

MS: m/e=582,0 ([M+H]+).

Example 229

Receiving (2,2-di-p-tolyl-benzo [1,3]dioxol-5-yl)-piperidine-1-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example g of bis(4-were)-meantion and (3,4-dihydroxy-phenyl)-piperidine-4-yl-methanone. Colorless foam.

MS: m/e=level of 414.2 ([M+H]+).

Example 230

Receiving (2,2-di-p-tolyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanone

Specified in the title compound was obtained is in accordance with the General method of example 233 g of bis(4-were)-meantion and (3,4-dihydroxy-phenyl)-morpholine-4-yl-methanone (example b). Colorless foam.

MS: m/e=416,2 ([M+H]+).

Example 231

Getting 4-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-research

Specified in the title compound was obtained in accordance with the General method of example 245 g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulphonylchloride (example b) and research. Yellow resin.

MS: m/e=478,1 ([M+H]+).

Example 232

Getting 4-(6-fluoro-2,2-di-p-tolyl-benzo[1,3]dioxol-5-sulfonyl)-research

Specified in the title compound was obtained in accordance with the General method of example g of bis(4-were)-meantion and 4-fluoro-5-(morpholine-1-sulfonyl)-benzene-1,2-diol (example b). Light brown resin.

MS: m/e 470,1 ([M+H]+).

Example 233

Obtain 1-{6-fluoro-10',11'-dihydrospiro[1,3-benzodioxole-2,5'-[5H]dibenzo[a,d]cyclohepten]-5-yl}sulfonyl]-piperidine

a) Obtaining 2-fluoro-4,5-dimethoxy-benzosulfimide

To a suspension of the complex of sulfur trioxide N,N-dimethylformamide (4,108 g, 27 mmol) in 1,2-dichloroethane was added dropwise 4-forwardly (3,49 g, 22 mmol). The mixture was slowly heated at 85°C in an oil bath. After 2.5 h, the solids were dissolved to obtain a Golden-yellow solution. Trace amount of starting compound still is guarded, and heating was continued for 4.5 hours the Oil bath was removed, and was added dropwise thionyl chloride (1,95 ml, 27 mmol). The mixture was heated 4 h at 85°and cooled to room temperature. The solution was poured into water and was extracted with dichloromethane (3×50 ml), the combined organic fraction was washed with water, dried over magnesium sulfate and evaporated. The remaining trace amounts of N,N-dimethylformamide was removed azeotrope with toluene to obtain the product as a colorless powder, which was used without further purification.

MS: m/e=254,0 ([M]+).

b) Obtaining 1-(2-fluoro-4,5-dimethoxy-benzazolyl)-piperidine

Piperidine (4,15 ml, 42,02 mmol) was slowly added to a chilled (ice bath) solution of 2-fluoro-4,5-dimethoxy-benzosulfimide (5 g, quintiles these figures were 19.63 mmol) in dichloromethane (110 ml). The mixture was stirred over night at room temperature, was diluted with dichloromethane and poured into water. The aqueous fraction was extracted with dichloromethane, the organic fractions were combined and washed with a saturated solution of sodium chloride, dried over magnesium sulfate and evaporated. The crude product was used without further purification.

NMR (300 MHz, CDCl3) cm: of 7.23 (d, 1H, J=6 Hz), of 6.71 (d, 1H, J=11 Hz), 3,93 (s, 3H), 3,90 (s, 3H), 3,14 (m, 4H), 1.70 to of 1.40 (m, 6H).

C) Obtaining 4-fluoro-5-(piperidine-1-sulfonyl)-benzene-1,2-diol

1 M solution of tribromide boron is dichloromethane (58 ml) was added dropwise to a chilled solution of 1-(2-fluoro-4,5-dimethoxy-benzazolyl)-piperidine (of 5.89 g, 19,42 mmol) in dichloromethane (100 ml), keeping the temperature between 10 and 20°C. the Mixture was stirred over night at room temperature and was poured into 1 M aqueous potassium dihydrophosphate and ice. After stirring for 1 h, the layers were separated and the aqueous fraction was extracted with ethyl acetate. The organic fractions were combined and washed with a saturated solution of sodium chloride, dried over magnesium sulfate and evaporated. The residue was purified column chromatography on silica gel (eluent 10:1 dichloromethane/methanol) to obtain the specified title compound as a brown resin (4,17 g, 78%).

MS: m/e=274,1 ([M-H]+).

g) Obtaining 1-{6-fluoro-10',11'-dihydrospiro[1,3-benzodioxole-2,5'-[5H]dibenzo[a,d]cyclohepten]-5-yl}sulfonyl]-piperidine

The mixture 2,3,6,7-dibenzocycloheptadiene-1-thione (0,281 g, 1.25 mmol), 4-fluoro-5-(piperidine-1-sulfonyl)-benzene-1,2-diol (0,230 g, 0.84 mmol), copper chloride(I) (0,207 g of 2.09 mmol) and triethylamine (and 0.46 ml, to 3.34 mmol) was heated in acetonitrile (5 ml) for 4 h at boiling under reflux. The mixture was cooled to room temperature and was filtered through a thin layer of silica gel, washing with a mixture of 1:1 ethyl acetate/heptane. The solvent was evaporated under reduced pressure, and the residue was purified column chromatography on silica gel (eluent 15:1 heptane/ethyl acetate) to give the product as a pale yellow foam (0,215 g, 55%).

MS: m/e=465,2 ([M] +).

Example 234

Getting 4-{6-fluoro-10',11'-dihydrospiro[1,3-benzodioxole-2,5'-[5H]dibenzo[a,d]cyclohepten]-5-yl}sulfonyl]-research

a) Obtaining 1-(2-fluoro-4,5-dimethoxy-benzazolyl)-piperidine

Specified in the title compound was obtained in accordance with the General method of example V of 2-fluoro-4,5-dimethoxy-benzosulfimide (example a) and research. Colorless powder, tPL107-108°C.

MS: m/e=305,1 ([M]+).

b) Obtain 4-fluoro-5-(morpholine-1-sulfonyl)-benzene-1,2-diol

Specified in the title compound was obtained in accordance with the General method of example V of 1-(2-fluoro-4,5-dimethoxy-benzazolyl)-piperidine (example 234a). Light brown powder.

MS: m/e=276,0 ([M-H]+).

C) Obtaining 4-{6-fluoro-10',11'-dihydrospiro[1,3-benzodioxole-2,5'-[5H]dibenzo[a,d]cyclohepten-5-yl}sulfonyl]-research

Specified in the title compound was obtained in accordance with the General method of example 233 g of 2,3,6,7-dibenzocycloheptadiene-1-thione and 4-fluoro-5-(morpholine-1-sulfonyl)-benzene-1,2-diol (example b). Light yellow powder.

MS: m/e=467,2 ([M]+).

Example 235

Getting 4-[{10',11'-dihydro-Spiro[1,3-benzodioxole-2,5'-[5H]dibenzo[a,d]cyclohepten]-5-yl}carbonyl]-research

Specified in the title compound was obtained according the General method of example 233 g of 2,3,6,7-dibenzocycloheptadiene-1-thione and (3,4-dihydroxy-phenyl)-morpholine-4-yl-methanone (example b). Light yellow resin.

MS: m/e=level of 414.2 ([M+H]+).

Example 236

Obtaining 1-[{10',11'-dihydro-Spiro[1,3-benzodioxole-2,5'-[5H]dibenzo[a,d]cyclohepten]-5-yl}carbonyl]-piperidine

Specified in the title compound was obtained in accordance with the General method of example g of 2,3,6,7-dibenzocycloheptadiene-1-thione and (3,4-dihydroxy-phenyl)-piperidine-4-yl-methanone. Light yellow resin.

MS: m/e=412,2 ([M+H]+).

Example 237

Obtaining [6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(3-methoxy-piperidine-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid (example a) and 3-methoxypiperidine. A colorless oil.

MS: m/e=470,1 ([M+H]+).

Example 240

Obtaining 1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-pyrrolidine

Specified in the title compound was obtained in accordance with the General method of example 245 g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulphonylchloride (example b) and pyrrolidine. Colorless powder.

MS: m/e=462,1 ([M+H+)].

Example 241

Obtaining 1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine

MS: m/e=476,1 ([M+H+)].

Example 242

Getting 4-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-thiomorpholine

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulphonylchloride (example b) and thiomorpholine. Colorless powder.

MS: m/e=494,1 ([M+H+]).

Example 243

Obtaining 1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-piperidine

Specified in the title compound was obtained in accordance with the General method of example 108b of 2,2',4,4'-tetrafluorodichloroethane (example a) and 4-fluoro-5-(piperidine-1-sulfonyl)-benzene-1,2-diol (example V). Light yellow resin.

MS: m/e=512,3 ([M+H]+).

Example 244

Obtaining 1-[2,2-bis-(2-chloro-4-fluoro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-piperidine

Specified in the title compound was obtained in accordance with the General method of example 108b of 2,2'-dichloro-4,4 diftormetilirovaniya (example a) and 4-fluoro-5-(piperidine-1-sulfonyl)-benzene-1,2-diol (example V). Colorless resin.

MS: m/e=544,1 ([M+H]+).

Example 245

Obtaining 1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-pyrrolidine

a) Receiving 5-bromo-2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxole

Specified in the title compound was obtained in accordance with the General method of example 108b of 2,2',4,4'-tetrafluorodichloroethane (example 207a) and 4-bromo-5-fluoro-benzene-1,2-diol (example 108A). Light yellow oil.

MS: m/e=444,0 ([M+H]+).

b) Obtain 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulinowo acid

To a cooled (-78° (C) to a solution of 5-bromo-2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxole (7,3 g, 16 mmol) in diethyl ether (48 ml) was added a solution of n-utility in hexane (1.6 M, 10.3 ml, 16 mmol, 1.0 equiv.). After 1 h at -78°after the solution was passed sulfur dioxide within 45 minutes the Reaction mixture was saturated with nitrogen and the reaction mixture was heated to 0°C. the Reaction was neutralized with hydrochloric acid (0,5 BC), was diluted with dichloromethane, and the organic fraction washed with water, dried over sodium sulfate, and volatile impurities were removed in vacuum. The accelerated cleanup chromatography resulted in the receipt specified in the connection header (4,2 g, 60%) as a white powder.

MS: m/e=427,0 ([M-H]-).

C) Obtaining 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulphonylchloride

To a solution of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulinowo acid (3.2 g, 7 mmol) in chloroform (25 ml) was added N-chlorosuccinimide (1.0 g, 7 mmol, and 1.0 is quiv.) at 20° C. After 40 min, the reaction mixture was filtered, and the filtrate was evaporated. The residue is suspended in dichloromethane, dried over sodium sulfate, and the solvent was removed in vacuum, getting listed in title product as a pale yellow resin.

MS: m/e=462,0 ([M+H]+).

g) Obtaining 1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-pyrrolidine

To a solution of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulphonylchloride (250 mg, 0.54 mmol) in diethyl ether (3 ml) was added pyrrolidine (of 0.11 ml, 1.35 mmol, 2.5 equiv.). The reaction mixture was diluted with ethyl acetate (50 ml), washed with an aqueous solution of hydrochloric acid (1 ad), a saturated solution of sodium chloride and water. The organic fraction was dried over sodium sulfate and volatile impurities were removed in vacuum. The accelerated cleanup chromatography resulted in the receipt specified in the title compound (198 mg, 74%) as a white foam.

MS: m/e=498,2 ([M+H]+).

Example 246

Obtaining 1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-4-fluoro-piperidine

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulphonylchloride (example 245v) and 4-foreveryday. The white foam.

MS: m/e=530,1 ([M+H]+).

Example 247

Obtaining 1-[2,2-bis(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-4,4-debtor-piperidine

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulphonylchloride (example 245v) and 4,4-deformability. The white foam.

MS: m/e=548,1 ([M+H]+).

Example 248

Obtaining 1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-4-trifluoromethyl-piperidine

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulphonylchloride (example 245v), and hydrochloride of 4-triftormetilfullerenov. The white foam.

MS: m/e=580,2 ([M+H]+).

Example 249

Getting 4-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-thiomorpholine

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulphonylchloride (example 245v) and thiomorpholine. The white foam.

MS: m/e=530,0 ([M+H]+).

Example 250

Obtaining 1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-2S-methoxymethyl-pyrrolidine

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-ft the p-benzo[1,3]dioxol-5-sulphonylchloride (example 245v) and (2S)-methoxypiperidine. The white foam.

MS: m/e=542,2 ([M+H]+).

Example 251

Obtain (2S-methoxymethyl-pyrrolidin-1-yl)-amide 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonic acid

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulphonylchloride (example 245v) and 1-amino-(2S)-methoxypiperidine. Yellow viscous oil.

MS: m/e=556,1 ([M-H]-).

Example 252

Obtain {1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-pyrrolidin-2S-yl}-methanol

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulphonylchloride (example 245v) and L-prolinol. The white foam.

MS: m/e=528,2 ([M-H]-).

Example 253

Obtaining 1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-pyrrolidin-3S-ol

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulphonylchloride (example 245v) and 3S-hydroxypyrrolidine. The white foam.

MS: m/e=514,2 ([M-H]-).

Example 254

Obtaining 1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-Piperi the Jn-4-ol

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulphonylchloride (example 245v) and 4-hydroxypiperidine. The white foam.

MS: m/e=528,2 ([M-N)-].

Example 255

Obtaining 1-[2,2-bis-(2-chloro-4,5-debtor-phenyl)6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-piperidine

Specified in the title compound was obtained in accordance with the General method of example 108b of 1,1'-(dihlormetilen)bis[2-chloro-4,5-diferently and 4-fluoro-5-(piperidine-1-sulfonyl)-benzene-1,2-diol (example V). Colorless foam.

MS: m/e=580,1 ([M+H]+).

Example 256

Getting 4-[{6-fluoro-10',11'-dihydro-Spiro[1,3-benzodioxole-2,5'-[5H]dibenzo[a,d]cyclohepten]-5-yl}-carbonyl]-research

Specified in the title compound was obtained in accordance with the General method of example g of 2,3,6,7-dibenzocycloheptadiene-1-thione and (2-fluoro-4,5-dihydroxy-phenyl)-morpholine-4-yl-methanone (example b). Light brown powder.

MS: m/e=432,3 ([M+H]+).

Example 257

Obtain (6-fluoro-2,2-di-p-tolyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example g of bis(4-were)-methane is ion and (2-fluoro-4,5-dihydroxy-phenyl)-morpholine-4-yl-methanone (example b). Light brown resin.

MS: m/e=434,3 ([M+H]+).

Example 258

Obtain 1-(6-fluoro-2,2-di-p-tolyl-benzo[1,3]dioxol-5-sulfonyl)-piperidine

Specified in the title compound was obtained in accordance with the General method of example g of bis(4-were)-meantion and 4-fluoro-5-(piperidine-1-sulfonyl)-benzene-1,2-diol (example V). Light yellow resin.

MS: m/e=470,2 ([M+H]+).

Example 259

Obtaining [6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

a) Receiving 5-bromo-6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxole

Specified in the title compound was obtained in accordance with the General method of example 108b, from 4-bromo-5-fluoro-benzene-1,2-diol (example 108A) and bis-(2-fluoro-phenyl)methanone (example a). Colorless powder.

MS: m/e=407,9 ([M]+).

b) Obtain 6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General method of example 108G of 5-bromo-6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxole and carbon dioxide. Light brown powder.

MS: m/e=371,2 ([M-H]+).

C) Obtaining [6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid and piperidine, with hexaflurophosphate (benzotriazol-1-yl-oxy-Tris-dimethylamino)-phosphonium (THIEF) as a condensing reagent (instead of carbonyldiimidazole) in acetonitrile as solvent at room temperature (reaction time 20 h). Colorless powder.

MS: m/e=440,3 ([M+H]+).

Example 260

Obtaining [6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-hydroxy-piperidine-1-yl)-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid and 4-hydroxy-piperidine, hexaflurophosphate (benzotriazol-1-yl-oxy-Tris-dimethylamino)-phosphonium (THIEF) as a condensing reagent (instead of carbonyldiimidazole) in acetonitrile as solvent at room temperature (reaction time 20 h). Colorless powder.

MS: m/e=456,2 ([M+H]+).

Example 261

Getting 4-fluoro-1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine

a) Obtaining 6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulinowo acid

Specified in the title compound was obtained in accordance with the General method of example b of 5-bromo-6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxole (example a). Colorless foam.

MS: m/e=to € 391.1 ([M-H]-).

b) Paul is an increase of 6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulphonylchloride

Specified in the title compound was obtained in accordance with the General method of example 245v of 6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulinowo acid (example a). A yellow oil.

MS: m/e=426,0 ([M+H]+).

C) Obtaining 4-fluoro-1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulphonylchloride (example b) and 4-foreveryday. The white foam.

MS: m/e=494,4 ([M+H]+).

Example 262

Getting 4,4-debtor-1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulphonylchloride (example b) and 4,4-deformability. The white foam.

MS: m/e=512,4 ([M+H]+).

Example 263

Obtaining 1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-4-trifluoromethyl-piperidine

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulphonylchloride (example b) and 4-(trifluoromethyl)-piperidineacetic. The white foam.

MS: m/e=544,4 ([M+H]+).

Example 264

Obtaining 1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-2S-methoxymethyl-pyrrolidine

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulphonylchloride (example b) and 2S-methoxypiperidine. The white foam.

MS: m/e=506,3 ([M+H]+).

Example 265

Obtaining 1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-pyrrolidin-3S-ol

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulphonylchloride (example b) and 3S-hydroxypyrrolidine. The white foam.

MS: m/e=478,2 ([M+H]+).

Example 266

Obtaining 1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine-4-ol

Specified in the title compound was obtained in accordance with the General method of example g of 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulphonylchloride (example b) and 4-hydroxypyrrolidine. White powder.

MS: m/e=491,1 ([M+H]+).

Example 267

Getting [2,2-bis-(3-chloro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

a) Obtaining bis-(3-chloro-phenyl)-methanol

It was soedineniya of 3-chloro-yogashala in accordance with example I; light yellow oil, MS: m/e=252 ([M]+).

b) Obtaining bis-(3-chloro-phenyl)-methanone

This compound was obtained from bis-(3-chloro-phenyl)-methanol according to example b; white powder, tPL: 117°MS: m/e=250 ([M]+).

C) Obtaining bis-(3-chloro-phenyl)-dichloromethane

This compound was obtained from bis-(3-chloro-phenyl)-methanone and PCl5in accordance with example V; MS: m/e=306 ([M]+).

g) obtaining the ethyl ester of 2,2-bis-(3-chloro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

This compound was obtained from bis-(3-chloro-phenyl)-dichloromethane and ethyl 3,4-dihydroxybenzoate in accordance with example g; yellow viscous oil, MS: m/e=415 ([M+H]+).

d) 2,2-bis-(3-chloro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

This compound was obtained from ethyl ether of 2,2-bis-(3-chloro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid in accordance with example d; white powder, tPL: 166°MS: m/e=386 ([M-H]-).

e) obtaining a [2,2-bis-(3-chloro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

This compound was obtained from 2,2-bis-(3-chloro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid and piperidine in accordance with example I; light yellow powder, tPL.: 54°C, MS: m/e=454 ([M+H]+).

Example 268

Getting [2,2-bis-(4-cyano-2-fluoro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

A mixture of [2,2-bis-(4-bromo-2-fluoro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone (0.3 g, 0.5 mmol), copper cyanide(I) (0,81 g), Tris(dibenzylideneacetone)diplegia(0) chloroform (78 mg), cyanide of tetraethylammonium (226 mg) and 1,1'-bis(diphenylphosphino)-ferrocene (165 mg) was boiled in 3 days in dioxane (8 ml). To the cooled mixture was added ethyl acetate (60 ml) and sodium bicarbonate (60 ml), the layers were separated, and the aqueous fraction was extracted with ethyl acetate. The organic fraction was decanted, washed with a saturated solution of sodium chloride and dried with sodium sulfate. Volatile impurities were removed, and the residue was purified by chromatography on silica gel (ethyl acetate/heptane) to obtain the specified title product as a pale yellow foam (0.17 g; 71%).

MS: m/e=491,1 ([M]+).

Example 269

Getting [2,2-bis-(3,5-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

a) Obtaining bis-(3,5-debtor-phenyl)-methanol

A mixture of 486 mg of magnesium, 8 ml of dry ether, a small amount of 3,5-debtor-bromine benzol and iodine was heated to initiate the Grignard reaction. Was added dropwise 2.38 ml 3,5-debtor-Brabanthal in 40 ml of dry ether and the mixture is boiled under reflux for one hour. Added 0,81 ml of ethylformate, and the mixture was stirred for 21 hours at room temperature. The reaction extinguished 7 m is 1 to N. hydrochloric acid, diluted with ethyl acetate and washed with water and saturated sodium chloride solution. Evaporation of the solvents and chromatography of the residue resulted in the receipt of 1.56 g of light yellow powder, tPL: 62°C; MS: 315 ([M+ASO]-).

b) Obtaining bis-(3,5-debtor-phenyl)-methanone

1.56 g of bis-(3,5-debtor-phenyl)-methanol, 1.06 g MnO2and 36 ml of 1,2-dichloroethane was heated under reflux for 4 hours. The mixture was cooled, filtered and evaporated. Chromatography of the residue resulted in the receipt of 1.47 g of a white powder, tPL: 79°C; MS: 254 ([M]+).

C) Obtaining bis-(3,5-debtor-phenyl)-dichloromethane

508 mg of bis-(3,5-debtor-phenyl)-methanone and 833 mg PCl5was placed in a sealed glass tube and heated at 170°C for 7 hours. The reaction mixture was diluted with dichloromethane and washed twice with water and ice. Evaporation of the solvent resulted in the receipt of 333 mg of a light yellow oil which was not purified further.

g) obtaining the ethyl ester of 2,2-bis-(3,5-debtor-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

239 mg of dichloro-bis(3,5-differenl)methane and 141 mg of ethyl-3,4-dihydroxybenzoate was heated at 180°C for 2 hours and 15 minutes to Brown the mixture was diluted with dichloromethane, washed the feast upon. a solution of NaHCO3and water. The dried solution was evaporated, and the residue was purified on silica gel with receipt is m 284 mg retinoid oil. MS: 419 ([M+H]+).

d) 2,2-bis-(3,5-debtor-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

267 mg of ethyl ester of 2,2-bis-(3,5-debtor-phenyl)-benzo[1,3]dioxol-5-carboxylic acid, and 3.8 ml of ethanol and 0.96 ml of 1 N. NaOH was stirred at room temperature for 6 hours the Solvent was evaporated and the residue was treated with ethyl acetate, diluted hydrochloric acid and water. Purification on silica gel led to obtain 204 mg of white crystals, tPL: 96°C; MS: 389 ([M-H]-).

e) obtaining a [2,2-bis-(3,5-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

96 mg of 2,2-bis-(3,5-debtor-phenyl)-benzo[1,3]dioxol-5-carboxylic acid, 93 mg of HBTU, 1 ml DMF and 50 mg N-methylmorpholine was stirred at room temperature. After 5 min was added 21 mg of piperidine, and the mixture was stirred at room temperature for 24 h the Mixture was diluted with ethyl acetate and washed twice with water. Evaporation of the solvent and purification on silica gel resulted in the receipt of 111 mg of a white foam, MS: 457 ([M]+).

Example 270

Getting [2,2-bis-(3,5-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

This compound was obtained from 2,2-bis-(3,5-debtor-phenyl)-benzo[1,3]dioxol-5-carboxylic acid and the research in accordance with example I; white foam, MS : 459 ([M]+).

Example 271

Getting 6-fluoro-[2,2-bis-(2-fluoro-FeNi is)-benzo[1,3]dioxol-5-yl]-[(S)-3-hydroxy-pyrrolidin-1-yl)]-methanone

Specified in the title compound was obtained in accordance with the General method of example g of 6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid and (S)-3-hydroxy-pyrrolidine, hexaflurophosphate (benzotriazol-1-yl-oxy-Tris-dimethylamino)-phosphonium (THIEF) as a condensing reagent (instead of carbonyldiimidazole) in acetonitrile as solvent at room temperature).

MS: m/e=442,3 ([M+H]+).

Example 272

Getting ethyl-methyl-amide 6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General method of example g of 6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid and ethyl-methyl-amine, with hexaflurophosphate (benzotriazol-1-yl-oxy-Tris-dimethylamino)-phosphonium (THIEF) as a condensing reagent (instead of carbonyldiimidazole) in acetonitrile as solvent at room temperature.

MS: m/e=414,3 ([M+H]+).

Example 273

Receive (2-methoxy-ethyl)-methyl-amide 6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the General method of example g of 6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dio the Sol-5-carboxylic acid and (2-methoxy-ethyl)-methyl-amine with hexaflurophosphate (benzotriazol-1-yl-oxy-Tris-dimethylamino)-phosphonium (THIEF) as a condensing reagent (instead of carbonyldiimidazole) in acetonitrile as solvent at room temperature.

MS: m/e=444,3 ([M+H]+).

Example 274

Getting [2,2-bis-(3,5-dichloro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

a) Obtaining bis-(3,5-dichloro-phenyl)-methanol

This compound was obtained from 3,5-dichloro-yogashala in accordance with example I; colourless powder, tPL: 126°C; MS: m/e=322 ([M]+).

b) Obtaining bis-(3,5-dichloro-phenyl)-methanone

This compound was obtained from bis-(3,5-dichloro-phenyl)-methanol according to example b; colourless powder, tPL: 157°C; MS: m/e=320 ([M]+).

C) Obtaining bis-(3,5-dichlorophenyl)dichloromethane

This compound was obtained from bis-(3,5-dichloro-phenyl)-methanone and PCl5in accordance with example V; light red powder.

g) obtaining the ethyl ester of 2,2-bis-(3,5-dichloro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

This compound was obtained from bis-(3,5-dichlorophenyl)dichloromethane and ethyl-3,4-dihydroxybenzoate in accordance with example g; light-red powder, tPL: 89°C; MS: m/e=484 ([M]+).

d) 2,2-bis-(3,5-dichloro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

This compound was obtained from ethyl ether of 2,2-bis-(3,5-dichloro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid in accordance with example d; white foam, MS: m/e=455 ([M-H]-).

e) obtaining a [2,2-bis-(3,5-Dich the EOS-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

This compound was obtained from 2,2-bis-(3,5-dichloro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid and piperidine in accordance with example I; wax-like powder, MS: m/e=([M+H]+).

Example 275

Getting [2,2-bis-(3,5-dichloro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

This compound was obtained from 2,2-bis-(3,5-dichloro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid and the research in accordance with example I; wax-like powder, MS: m/e=526 ([M+H]+).

Example 276

Getting [2,2-bis-(3-bromo-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

a) Obtaining bis-(3-bromophenyl)-dichloromethane

340 mg of bis-(3-bromo-phenyl)-methanone, and 0.08 ml of DMF and 5 ml of thionyl chloride are boiled under reflux for 24 hours. The solvent was evaporated in vacuum to obtain a colorless wax-like powder, MS: m/e=394 ([M]+).

b) obtaining a [2,2-bis-(3-bromo-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

79 mg of bis-(3-bromophenyl)-dichloromethane and 48 mg (2-fluoro-4,5-dihydroxy-phenyl)-morpholine-4-yl-methanone was heated at 180°C for one hour. Chromatography of the dark residue was led to 30 mg of a colorless wax-like powder, MS: m/e=564 ([M+H]+).

Example 277

Obtaining [6-fluoro-2,2-bis-(3-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-the-methanone

a) Obtaining dichloro-bis-(3-methoxyphenyl)-methane

This compound was obtained in accordance with example a; brown liquid.

b) Receiving [6-fluoro-2,2-bis-(3-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

This compound was obtained in accordance with example b; light brown wax-like powder, MS: m/e=466 ([M+H]+).

Example 278

Getting [2,2-bis-(3-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

a) obtaining the ethyl ester of 2,2-bis-(3-methoxy-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

This compound was obtained from dichloro-bis-(3-methoxyphenyl)-methane and ethyl-3,4-dihydroxybenzoate in accordance with example h; the crude product was used in the next stage.

b) Obtain 2,2-bis-(3-methoxy-phenyl)-benzo[1,3]dioxol-5-carboxylic acid

This compound was obtained from ethyl ether of 2,2-bis-(3-methoxy-phenyl)-benzo[1,3]dioxol-5-carboxylic acid in accordance with example d; wax-like powder, MS: m/e=377 ([M-H]-).

C) obtaining a [2,2-bis-(3-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanone

This compound was obtained from 2,2-bis-(3-methoxy-phenyl)-benzo[1,3]dioxol-5-carboxylic acid and piperidine in accordance with example I; wax-like powder, MS: m/e=446 ([M+H]+].

Example 279

ruchanie [2,2-bis-(3-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanone

This compound was obtained from bis-(3-chloro-phenyl)-dichloromethane (2-fluoro-4,5-dihydroxy-phenyl)-morpholine-4-yl-methanone in accordance with example b; viscous brown oil, MS: m/e=474 ([M+H]+).

Examples of galenic compositions

Example

Tablets, film-coated, containing the following ingredients can be obtained in the usual way:

IngredientsOn
pill
Engine:
The compound of formula (I)10.0 mg200.0 mg
Microcrystalline cellulose23,5 mgto 43.5 mg
Anhydrous lactose60,0 mg70.0 mg
Povidone K12.5 mg15,0 mg
Nitroglicerine starch12.5 mg17,0 mg
Magnesium stearate1.5 mg4.5 mg
(Kernel weight)120,0 mg350,0 mg
Film coating:
The hypromellose3.5 mg7,0 mg
Poly is trangleball 6000 0.8 mg1.6 mg
Talc1.3 mg2.6 mg
Iron oxide (yellow)0.8 mg1.6 mg
Titanium dioxide0.8 mg1.6 mg

The active ingredient was sieved and mixed with microcrystalline cellulose, and the mixture was granulated with a solution of polyvinylpyrrolidone in water. The granulate was mixed with Nitroglycerinum starch and magnesium stearate and compressed to obtain cores 120 or 350 mg, respectively. The core was coated with an aqueous solution/suspension of the above film coating.

Example B

Capsules containing the following ingredients can be obtained in the usual way:

IngredientsOn capsule
The compound of formula (I)25.0 mg
Lactose150,0 mg
Corn starch20.0 mg
Talc5.0 mg

Components are sieved and mixed, and the mixture was filled capsules of size 2.

The example In

Injectable solutions may have the following composition:

The compound of formula (I)3.0 mg
The polyethylene glycol 400 150,0 mg
Acetic acidto pH 5.0
Water for injection solutionsto 1.0 ml

The active ingredient was dissolved in a mixture of polyethylene glycol 400 and water for injection (part). the pH was brought to 5.0 using acetic acid. The volume was made up to 1.0 ml by adding the remaining amount of water. The solution was filtered, filled into capsules of suitable size and sterilized.

1. Benzodioxole formula (I)

where R1and R2independently represent unsubstituted phenyl or phenyl which is mono-, di - or tizamidine, independently, hydroxy, lower alkyl, lower alkoxy, PERFLUORO-lower alkyl, PERFLUORO-lower alkoxy, cyano, nitro or halogen; or R1and R2together with the carbon atom to which they are attached, form a residue 10',11'-dihydro-2,5'-[5H]dibenzo[a,d]cycloheptene;

R3and R4independently represent hydrogen, halogen or hydroxy;

R5represents hydrogen, lower alkyl, lower alkylsulfonyl, cycloalkyl lower alkyl or hydroxy-lower alkyl;

R6is a Y-R8, lower alkyl, lower alkoxy, hydroxy-lower alkyl, lower alkoxy-lower alkyl, lower alkylaminocarbonyl-n is SSI alkyl, heterocyclyl selected from morpholino, tetrahydrofuranyl, pyrrolidinyl, piperidinyl and azepane, cycloalkyl, phenyl or vanillasky alkyl, where the phenyl group can be optionally substituted lower alkoxy, or

R6represents hydrogen, when X represents-C(O)- or-SO2-;

or

R5and R6together with the nitrogen atom to which they are attached, form a piperazinil, morpholino, piperidinyl, piperidine-4-one, pyrrolidinyl, thiomorpholine, azepane, 1,2,3,4-tetrahydro-ethenolysis, 1,2,3,6-tetrahydro-pyridinyl, [1,4]-diazepan, 1,4-dioxa-8-Aza-Spiro[4.5]Dec-8-yl, 2,3,5,6-tetrahydro-[1,2']bipyridinyl-4-yl and 3-hydroxy-8-Aza-bicyclo[3,2,1.]Oct-8-yl, optionally mono-, di - or tizamidine, independently, lower alkyl, lower alkoxycarbonyl, hydrokinesis the alkyl, lower alkoxy-lower alkyl, dignissim allylcarbamate, carbamoyl, lower alkylcarboxylic, oxo, dioxo, alkanoyl, hydroxy, lower alkoxy, halogen, PERFLUORO-lower alkyl, heteroaryl selected from the group including pyridinyl, pyrazinyl and pyrimidinyl, or phenyl or fininished-alkyl, where the phenyl group may be optionally mono-, di - or tizamidine, independently, lower alkyl, lower alkoxy, halogen or PERFLUORO-lower alkyl.

R7represents odor is d, halogen, lower alkyl or cyano;

R8represents phenyl, cycloalkyl selected from morpholino, tetrahydrofuranyl, pyrrolidinyl, piperidinyl and azepane; or heteroaryl selected from the group including pyridinyl, pyrazinyl and pyrimidinyl;

X represents a single bond, -CH2-, -C(O)- or-SO2-;

Y represents-CH2-, -C(O)-, -NH - or-SO2-;

and their pharmaceutically acceptable salts, except

methylamide 2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid,

methylamide 4-methyl-2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid,

ethylamide 7-hydroxy-2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid and

n-propylamide 7-hydroxy-2,2-diphenyl-benzo[1,3]dioxol-5-carboxylic acid.

2. Benzodioxole according to claim 1, where R1and R2independently represent a phenyl, optionally mono-, di - or tizamidine, independently, hydroxy, lower alkyl, lower alkoxy, PERFLUORO-lower alkyl, alkanoyl, cyano or halogen;

R3and R4independently represent hydrogen, halogen or hydroxy,

R5represents hydrogen or lower alkyl;

R6represents phenyl or vanillasky alkyl, where the phenyl group may be optionally mono-, di - or trisomies is authorized, independently, lower alkyl, lower alkoxy, halogen, PERFLUORO-lower alkyl, hydroxy, alkanoyl or cyano;

R5and R6together with the nitrogen atom to which they are attached, form a piperazinil, morpholino, piperidinyl, piperidine-4-one, pyrrolidinyl, thiomorpholine, azepane, 1,2,3,4-tetrahydro-ethenolysis, 1,2,3,6-tetrahydro-pyridinyl, [1,4]-diazepan, 1,4-dioxa-8-Aza-Spiro[4.5]Dec-8-yl, 2,3,5,6-tetrahydro-[1,2']bipyridinyl-4-yl and 3-hydroxy-8-Aza-bicyclo[3,2,1.]Oct-8-yl, optionally mono-, di - or tizamidine, independently, lower alkyl, lower alkoxycarbonyl, hydrokinesis the alkyl, lower alkoxy-lower alkyl, dignissim allylcarbamate, carbamoyl, lower alkylcarboxylic, oxo, dioxo, alkanoyl, hydroxy, lower alkoxy, halogen, PERFLUORO-lower alkyl, heteroaryl selected from the group including pyridinyl, pyrazinyl and pyrimidinyl, or phenyl or fininished-alkyl, where the phenyl group may be optionally mono-, di - or tizamidine, independently, lower alkyl, lower alkoxy, halogen or PERFLUORO-lower alkyl;

R7represents hydrogen;

X represents-CH2-, -C(O)- or-SO2-;

and their pharmaceutically acceptable salts.

3. Benzodioxole according to claim 1 or 2, where R1and R2independently represent unsubstituted f the Nile or phenyl, which is mono-, di - or tizamidine, independently, lower alkyl, lower alkoxy, PERFLUORO-lower alkyl, PERFLUORO-lower alkoxy, cyano, nitro or halogen.

4. Benzodioxole according to claim 1, where R1and R2independently represent phenyl, which is mono - or disubstituted, independently, by halogen or lower alkoxy.

5. Benzodioxole according to claim 1, where R1and R2together with the carbon atom to which they are attached, form a residue 10',11'-dihydro-2,5'-[5H]dibenzo[a,d]cycloheptene.

6. Benzodioxole according to claim 1, where R3and R4independently represent hydrogen.

7. Benzodioxole according to claim 1, where R5and R6together with the nitrogen atom to which they are attached, form piperidinyl, morpholino, thiomorpholine or pyrrolidinyl, optionally mono - or disubstituted, independently, by hydroxy or by halogen.

8. Benzodioxole according to claim 1, where R5represents hydrogen, lower alkyl, lower alkylsulfonyl, cycloalkenyl alkyl or hydroxy-lower alkyl.

9. Benzodioxole according to claim 1, where R6is a Y-R8, lower alkyl, lower alkoxy, hydroxy-lower alkyl, lower alkoxy-lower alkyl, lower allylcarbamate-lower alkyl, heterocyclyl, cycloalkyl, phenyl or phenyl lower alkyl, where the phenyl group may be optionally mono-, di - or tizamidine follows the IMO, lower alkyl, lower alkoxy, halogen, PERFLUORO-lower alkyl, hydroxy, alkanoyl or piano.

10. Benzodioxole according to claim 1, where R7represents hydrogen.

11. Benzodioxole according to claim 1, where R7represents cyano, halogen or lower alkyl.

12. Benzodioxole according to claim 1, where R8represents morpholino, piperidinyl or azepane.

13. Benzodioxole according to claim 1, where X represents-C(O)- or-SO2-.

14. Benzodioxole according to claim 1, where Y represents-CH2- or-NH-.

15. Benzodioxole according to claim 1, selected from the following groups:

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-piperidine,

1-(4-chloro-phenyl)-4-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-piperazine,

1-(2,3-dimethyl-phenyl)-4-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-piperazine,

1-(2,4-dichloro-phenyl)-4-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-piperazine,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(4-fluoro-phenyl)-piperazine,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(3-chloro-phenyl)-piperazine,

4-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-morpholine,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-phenyl-piperazine,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-pyrrolidin,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(3-methoxy-phenyl)-piperazine,

1-(2,2-diphenyl-benzo[1,3]dioc the ol-5-sulfonyl)-4-(4-methoxy-phenyl)-piperazine,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(2-methoxy-phenyl)-piperazine,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(2-chloro-phenyl)-piperazine,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(2-fluoro-phenyl)-piperazine,

phenethyl-amide 2,2-diphenyl-benzo[1,3]dioxol-5-sulfonic acid,

1-benzo[1,3]dioxol-5-yl-4-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-piperazine,

4-benzyl-1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-piperidine,

2-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-1,2,3,4-tetrahydro-isoquinoline,

benzyl-methyl-amide 2,2-diphenyl-benzo[1,3]dioxol-5-sulfonic acid,

benzylated 2,2-diphenyl-benzo[1,3]dioxol-5-sulfonic acid,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-methyl-[1,4]diazepan,

1-(3-chloro-5-trifluoromethyl-pyridine-2-yl)-4-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-[1,4]diazepan,

phenylamide 2,2-diphenyl-benzo[1,3]dioxol-5-sulfonic acid,

[2-(4-methoxy-phenyl)-ethyl]-amide 2,2-diphenyl-benzo[1,3]dioxol-5-sulfonic acid,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-methyl-piperazine,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-(4-fluoro-phenyl)-1,2,3,6-tetrahydro-pyridine,

4-(4-chloro-phenyl)-1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-1,2,3,6-tetrahydro-pyridine,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-sulfonyl)-4-Fe is Il-1,2,3,6-tetrahydro-pyridine,

racemic 1-[2-(2-chloro-phenyl)-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

racemic 1-[2-(2-chloro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

racemic 1-[2-(2-chloro-phenyl)-2-p-tolyl-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

racemic 1-[2-(4-chloro-phenyl)-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

racemic 1-[2-(4-chloro-phenyl)-2-p-tolyl-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

1-[2,2-bis-(4-chloro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

racemic 1-[2-(4-fluoro-phenyl)-2-phenyl-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

racemic 1-[2-(4-methoxy-phenyl)-2-phenyl-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

racemic 1-[2-(4-chloro-phenyl)-2-p-tolyl-benzo[1,3]dioxol-5-sulfonyl]-4-(4-fluoro-phenyl)-1,2,3,6-tetrahydro-pyridine,

racemic 1-[2-(4-chloro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

racemic 1-[2-(2,4-dichloro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

1-[2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

racemic 1-[2-(3-chloro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

racemic 1-[2-(4-chloro-phenyl)-2-(2-chloro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

racemic (2,2-diphenyl-benzo,3]dioxol-5-yl)-(3-hydroxy-pyrrolidin-1-yl)-methanon,

4-(2,2-diphenyl-benzo[1,3]dioxol-5-carbonyl)-piperazine-1-carbaldehyde,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-hydroxymethyl-piperidine-1-yl)-methanon,

(1,4-dioxa-8-Aza-Spiro[4.5]Dec-8-yl)-(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-methanon,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanon,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-methyl-piperazine-1-yl)-methanon,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-isopropyl-piperazine-1-yl)-methanon,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-carbonyl)-piperidine-4-one,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-hydroxy-piperidine-1-yl)-methanon,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-pyrrolidin-1-yl-methanon,

racemic ethyl ester 1-(2,2-diphenyl-benzo[1,3]dioxol-5-carbonyl)-piperidine-3-carboxylic acid,

[4-(5-chloro-2-methoxy-phenyl)-piperazine-1-yl]-(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-methanon,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-m-tolyl-piperazine-1-yl)-methanon,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanon,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-o-tolyl-piperazine-1-yl)-methanon,

racemic ethyl ester 1-(2,2-diphenyl-benzo[1,3]dioxol-5-carbonyl)-piperidine-2-carboxylic acid,

[4-(2,3-dichloro-phenyl)-piperazine-1-yl]-(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-methanon,

[4-(4-chloro-3-trifluoromethyl-phenyl)-Pieper is Zin-1-yl]-(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-methanon,

racemic (2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(3-hydroxymethyl-piperidine-1-yl)-methanon,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(2,3,5,6-tetrahydro-[1,2']bipyridinyl-4-yl)-methanon,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-pyridin-2-yl-piperazine-1-yl)-methanon,

(4-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-methyl-piperazine-1-yl)-methanon,

(4-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanon,

(4-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanon,

(4,7-dichloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanon,

(4,7-dichloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanon,

(4,7-dichloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-methyl-piperazine-1-yl)-methanon,

(7-bromo-4-chloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-(4-methyl-piperazine-1-yl)-methanon,

(7-bromo-4-chloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanon,

(7-bromo-4-chloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanon,

(7-hydroxy-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanon,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-[4-(4-fluoro-phenyl)-3,6-dihydro-2H-pyridine-1-yl]-methanon,

1-(2,2-diphenyl-benzo[1,3]dioxol-5-ylmethyl)-4-(4-fluoro-phenyl)-1,2,3,6-tetrahydro-pyridine,

and their pharmaceutically acceptable salts.

16. Benzodioxole according to claim 1, selected from the following groups:

N-(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-benzosulfimide,

N,N-bis(methylsulphonyl)-2,2-diphenyl-1,3-benzodioxol-5-amine,

N,N-bis(butylsulfonyl)-2,2-diphenyl-1,3-benzodioxol-5-amine,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-amide cyclohexanecarbonyl acid,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-amide butane-1-sulfonic acid,

N-(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-butyramide,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-amide morpholine-4-carboxylic acid,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-amide piperidine-1-sulfonic acid,

(2,2-diphenyl-benzo[1,3]dioxol-5-yl)-amide piperidine-1-carboxylic acid,

[2-(4-chloro-phenyl)-2-(2-fluoro-4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

4-[2-(4-chloro-phenyl)-2-(2-fluoro-4-methoxy-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-morpholine,

[2-(4-methoxy-phenyl)-2-(3-nitro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

4-[2-(4-methoxy-phenyl)-2-(3-nitro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-morpholine,

4-[2-(4-methoxy-phenyl)-5-(morpholine-4-carbonyl)-benzo[1,3]dioxol-2-yl]-benzonitrile,

4-[2-(4-methoxy-phenyl)-5-(morpholine-4-sulfonyl)-benzo[1,3]dioxol-2-yl]-benzonitrile,

[2-(2-fluoro-4-methoxy-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

4-[2-(2-fluoro-4-methoxy-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-Sul is of IMT]-morpholine,

(6-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[6-fluoro-2-(4-fluoro-phenyl)-2-phenyl-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2-(2-chloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

(6-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanon,

[6-fluoro-2-(4-fluoro-phenyl)-2-phenyl-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2-(2-chloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

(6-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-[4-(4-fluoro-phenyl)-piperazine-1-yl]-methanon,

[6-fluoro-2-(4-fluoro-phenyl)-2-phenyl-benzo[1,3]dioxol-5-yl]-[4-(4-fluoro-phenyl)-piperazine-1-yl]-methanon,

[2-(2-chloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-[4-(4-fluoro-phenyl)-piperazine-1-yl]-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-[4-(4-fluoro-phenyl)-piperazine-1-yl]-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

(6-methyl-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidin-1-yl-methanon,

[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

(6-bromo-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanon,

(+)-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

(-)-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2-(2,4-dichloro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2-(2,4-dichloro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

(6-chloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanon,

(6-chloro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanon,

ethyl-methyl-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

methyl-propyl-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(2-methyl-pyrrolidin-1-yl)-methanon,

azepin-1-alamid 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

azetidin-1-yl-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-methanon,

azepin-1-yl-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-methanon,

(2,2-dimethyl-1-methylcarbamoyl-propyl)-amid-(2,4-dichloro-phenyl)-6-fluoro-2-(-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(2S-methoxymethyl-pyrrolidin-1-yl)-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(2R-hydroxymethyl-pyrrolidin-1-yl)-methanon,

dimethylamide 1-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carbonyl]-pyrrolidin-2R-carboxylic acid,

cyclobutylamine 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

morpholine-4-alamid 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(2,3,5,6-tetrahydro-[1,2']bipyridinyl-4-yl)-methanon,

amide 1-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carbonyl]-pyrrolidin-2S-carboxylic acid,

tert-butoxy-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

cyclopentylamine 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

(tetrahydro-furan-2-ylmethyl)-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-thiomorpholine-4-yl-methanon,

isopropylated 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

the feast is ridin-1-alamid 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

methoxy-methyl-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(3R-hydroxy-pyrrolidin-1-yl)-methanon,

bis-cyclopropylmethyl 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-fluoro-piperidine-1-yl)-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(1,4-dioxa-8-Aza-Spiro[4.5]Dec-8-yl)-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-hydroxymethyl-piperidine-1-yl)-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-hydroxy-4-methyl-piperidine-1-yl)-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-pyrrolidin-1-yl-methanon,

N-{1-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carbonyl]-pyrrolidin-3S-yl}-acetamide", she

cycloheptylamine 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

N'-pyridin-2-yl-hydrazide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

(2S-methoxymethyl-pyrrolidin-1-yl)-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

[2-(2,4-dichloro-phenyl)-6-the Thor-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(1,1-dioxo-thiomorpholine-4-yl)-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(3-hydroxy-8-Aza-bicyclo[3,2,1]Oct-8-yl)-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(2R-methoxymethyl-pyrrolidin-1-yl)-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(3S-hydroxy-pyrrolidin-1-yl)-methanon,

N-{1-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carbonyl]-pyrrolidin-3R-yl}-acetamide", she

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(2S-hydroxymethyl-pyrrolidin-1-yl)-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-retention,

[2-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

6-(morpholine-4-carbonyl)-2,2-diphenyl-benzo[1,3]dioxol-5-carbonitril,

[2-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-pyrrolidin-1-yl-methanon,

[2,2-bis-(2,4-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(2,4-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-pyrrolidin-1-yl-methanon,

[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[,2-bis-(4-bromo-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

4-[2,2-bis-(4-cyano-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carbonyl]-morpholine,

4-[2-(4-bromo-phenyl)-5-fluoro-6-(morpholine-4-carbonyl)-benzo[1,3]dioxol-2-yl]-benzonitrile,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(4-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[6-chloro-2,2-bis-(2,4-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2-(2-chloro-4-fluoro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

4-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-morpholine,

4-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-morpholine,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4,4-debtor-piperidine-1-yl)-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-trifluoromethyl-piperidine-1-yl)-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(3S-ethoxy-pyrrolidin-1-yl)-methanon,

(1R-phenyl-ethyl)-amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(1 of the co-thiomorpholine-4-yl)-methanon,

[2,2-bis-(2-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[6-fluoro-2,2-bis-(4-trifluoromethyl-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[6-fluoro-2,2-bis-(3-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2-(2-chloro-4-fluoro-phenyl)-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(3,4-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2,2-bis-(3,4-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(3-hydroxy-pyrrolidin-1-yl)-methanon,

[2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(4-hydroxy-piperidine-1-yl)-methanon,

ethyl-methyl-amide 2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid,

bis-(2-hydroxy-ethyl)-amide 2,2-bis-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-carboxylic acid,

[2,2-bis-(4-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2,2-bis-(4-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-pyrrolidin-1-yl-methanon,

[2,2-bis-(2-chloro-4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2,2-bis-(3,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(2,5-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(2-chloro-4-fluoro-phenyl)-be the AOR[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(2-chloro-4-fluoro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[6-chloro-2,2-bis-(2-chloro-4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

amide 2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

[2,2-bis-(4-bromo-2-fluoro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(3,4-cis-dihydroxy-pyrrolidin-1-yl)-methanon,

[2,2-bis-(2,3-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[6-fluoro-2,2-bis-(4-triptoreline-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(2-chloro-4,5-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

4-[2,2-bis-(2-chloro-4-fluoro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-morpholine,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(4-fluoro-piperidine-1-yl)-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(4,4-debtor-piperidine-1-yl)-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(4-trifluoromethyl-piperidine-1-yl)-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(4-hydroxy-piperidine-1-yl)-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-t is morpholin-4-yl-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-pyrrolidin-1-yl-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(3S-hydroxy-pyrrolidin-1-yl)-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(2S-hydroxymethyl-pyrrolidin-1-yl)-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(2S-methoxymethyl-pyrrolidin-1-yl)-methanon,

(6-chloro-2,2-di-p-tolyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanon,

4-[{6-chloro-10',11'-dihydro-Spiro[1,3-benzodioxole-2,5'-[5H]dibenzo[a,d]cyclohepten]-5-yl}carbonyl]-morpholine,

[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-fluoro-piperidine-1-yl)-methanon,

(4,4-debtor-piperidine-1-yl)-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-methanon,

[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-trifluoromethyl-piperidine-1-yl)-methanon,

[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-thiomorpholine-4-yl-methanon,

(3S-ethoxy-pyrrolidin-1-yl)-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-methanon,

[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-[(S)-(2-methoxymethyl-pyrrolidin-1-yl)]-methanon,

[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-[(S)-2-hydroxymethyl-pyrrolidin-1-yl]-methanon,

[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-[(S)-3-hydroxy-pyrrolidin-1-yl]-methanon,

[For-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-hydroxy-piperidine-1-yl)-methanon,

4-[2,2-bis-(2-chloro-4,5-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-morpholine,

(2,2-di-p-tolyl-benzo[1,3]dioxol-5-yl)-piperidine-1-yl-methanon,

(2,2-di-p-tolyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanon,

4-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-morpholine,

4-(6-fluoro-2,2-di-p-tolyl-benzo[1,3]dioxol-5-sulfonyl)-morpholine,

1-{6-fluoro-10',11'-dihydrospiro[1,3-benzodioxole-2,5'-[5H]dibenzo[a,d]cyclohepten]-5-yl}sulfonyl]-piperidine,

4-{6-fluoro-10',11'-dihydrospiro[1,3-benzodioxole-2,5'-[5H]dibenzo[a,d]cyclohepten]-5-yl}sulfonyl]-morpholine,

4-[{10',11'-dihydro-Spiro[1,3-benzodioxole-2,5'-[5H]dibenzo[a,d]cyclohepten]-5-yl}carbonyl]-morpholine,

1-[{10',11'-dihydro-Spiro[1,3-benzodioxole-2,5'-[5H]dibenzo[a,d]cyclohepten]-5-yl}carbonyl]-piperidine,

[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(3-methoxy-piperidine-1-yl)-methanon,

1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-pyrrolidin,

1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

4-[6-fluoro-2,2-bis-(ftor-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-thiomorpholine,

1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

1-[2,2-bis-(2-chloro-4-fluoro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dio the Sol-5-sulfonyl]-pyrrolidin,

1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-4-fluoro-piperidine,

1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-4,4-debtor-piperidine,

1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-4-trifluoromethyl-piperidine,

4-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-thiomorpholine,

1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-2S-methoxymethyl-pyrrolidine,

(2S-methoxymethyl-pyrrolidin-1-yl)-amide 2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonic acid,

{1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-pyrrolidin-2S-yl}-methanol,

1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-pyrrolidin-3S-ol,

1-[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-piperidine-4-ol,

1-[2,2-bis-(2-chloro-4,5-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

4-[{6-fluoro-10',11'-dihydro-Spiro[1,3-benzodioxole-2,5'-[5H]dibenzo[a,d]cyclohepten]-5-yl}-carbonyl]-morpholine,

(6-fluoro-2,2-di-p-tolyl-benzo[1,3]dioxol-5-yl)-morpholine-4-yl-methanon,

1-(6-fluoro-2,2-di-p-tolyl-benzo[1,3]dioxol-5-sulfonyl)-piperidine,

[6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-hydroxy-Piperi the Jn-1-yl)-methanon,

4-fluoro-1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

4,4-debtor-1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine,

1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-4-trifluoromethyl-piperidine,

1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-2-methoxymethyl-pyrrolidin,

1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-pyrrolidin-3S-ol,

1-[6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-sulfonyl]-piperidine-4-ol,

[2,2-bis-(3-chloro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2,2-bis-(4-cyano-2-fluoro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(3,5-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2,2-bis-(3,5-debtor-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

6-fluoro-[2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-[(S)-3-hydroxy-pyrrolidin-1-yl)]-methanon,

ethyl-methyl-amide 6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

(2-methoxy-ethyl)-methyl-amide 6-fluoro-2,2-bis-(2-fluoro-phenyl)-benzo[1,3]dioxol-5-carboxylic acid,

[2,2-bis-(3,5-dichloro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2,2-bis-(3,5-dichloro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(3-bromo-phenyl)-6-fluoro-benzo[1,3]diox is l-5-yl]-morpholine-4-yl-methanon,

[6-fluoro-2,2-bis-(3-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(3-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2,2-bis-(3-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-metano

and their pharmaceutically acceptable salts.

17. Benzodioxole according to claim 1, selected from the following groups:

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-methoxy-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

(+)-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

(-)-[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-thiomorpholine-4-yl-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4-fluoro-piperidine-1-yl)-methanon,

[2-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2-(4-chloro-phenyl)-2-(2,4-d is chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-pyrrolidin-1-yl-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-(4,4-debtor-piperidine-1-yl)-methanon,

[2,2-bis-(4-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-piperidine-1-yl-methanon,

[2,2-bis-(4-chloro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-pyrrolidin-1-yl-methanon,

[2,2-bis-(4-bromo-2-fluoro-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-morpholine-4-yl-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(4,4-debtor-piperidine-1-yl)-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(4-hydroxy-piperidine-1-yl)-methanon,

[2,2-bis-(2,4-debtor-phenyl)-6-fluoro-benzo[1,3]dioxol-5-yl]-(3S-hydroxy-pyrrolidin-1-yl)-methanon

and their pharmaceutically acceptable salts.

18. Pharmaceutical composition having cannabidiol SW antagonistic activity comprising the compound according to claim 1 and a pharmaceutically acceptable carrier and/or adjuvant.

19. The use of benzodioxole formula (I)

where R1and R2independently represent unsubstituted phenyl or phenyl which is mono-, di - or tizamidine, independently, hydroxy, lower alkyl, lower alkoxy, PERFLUORO-lower alkyl, PERFLUORO-lower alkoxy, cyano, nitro or halogen; or R1and 2together with the carbon atom to which they are attached, form a residue 10',11'-dihydro-2,5'-[5H]dibenzo[a,d]cycloheptene;

R3and R4independently represent hydrogen, halogen or hydroxy;

R5represents hydrogen, lower alkyl, lower alkylsulfonyl, cycloalkyl lower alkyl or hydroxy-lower alkyl;

R6is a Y-R8, lower alkyl, lower alkoxy, hydroxy-lower alkyl, lower alkoxy-lower alkyl, lower alkylaminocarbonyl-lower alkyl, heterocyclyl selected from morpholino,

tetrahydrofuranyl, pyrrolidinyl, piperidinyl and azepane, cycloalkyl, phenyl or vanillasky alkyl, where the phenyl group can be optionally substituted lower alkoxy, or

R6represents hydrogen, when X represents-C(O)- or-SO2-;

or

R5and R6together with the nitrogen atom to which they are attached, form a piperazinil, morpholino, piperidinyl, piperidine-4-one, pyrrolidinyl, thiomorpholine, azepane, 1,2,3,4-tetrahydro-ethenolysis, 1,2,3,6-tetrahydro-pyridinyl, [1,4]-diazepan, 1,4-dioxa-8-Aza-Spiro[4.5]Dec-8-yl, 2,3,5,6-tetrahydro-[1,2']bipyridinyl-4-yl and 3-hydroxy-8-Aza-bicyclo[3,2,1.]Oct-8-yl, optionally mono-, di - or tizamidine, independently, lower alkyl, lower alkoxycarbonyl, guy is rosenschon-alkyl, lower alkoxy-lower alkyl, dignissim allylcarbamate, carbamoyl, lower alkylcarboxylic, oxo, dioxo, alkanoyl, hydroxy, lower alkoxy, halogen, PERFLUORO-lower alkyl, heteroaryl selected from the group including pyridinyl, pyrazinyl or pyrimidinyl, or phenyl or fininished-alkyl, where the phenyl group may be optionally mono-, di - or tizamidine, independently, lower alkyl, lower alkoxy, halogen or PERFLUORO-lower alkyl.

R7represents hydrogen, halogen, lower alkyl or cyano;

R8represents phenyl, cycloalkyl selected from morpholino, tetrahydrofuranyl, pyrrolidinyl or piperidinyl and azepane; or heteroaryl selected from the group including pyridinyl, pyrazinyl and pyrimidinyl;

X represents a single bond, -CH2-, -C(O)- or-SO2-;

Y represents-CH2-, -C(O)-, -NH - or-SO2-;

and their pharmaceutically acceptable salts to obtain drugs for the treatment and/or prevention of diseases associated with modulation SW receptors.



 

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The invention relates to a derivative (azetidin-1-illlil)lactams of the formula (I) and their pharmaceutically acceptable salts, where R - (C1-C6)-alkyl, optionally substituted by-COOH, -COO((C1-C4)-alkyl), (C3-C7-cycloalkyl, aryl or het1and (C3-C7-cycloalkyl, optionally substituted with 1-2 substituents selected from (C1-C4)-alkyl and fluorine; R1is phenyl, optionally substituted by 1-2 halosubstituted; R2- -CONR3R4, -CONR5((C3-C7-cycloalkyl), -NR3R4that gets3or a group of formula (a), (b), (C); X - (C1-C4-alkylene; X1- directional communication, X2- directional communication or CO; m = 1; used in the treatment of diseases by producing antagonistic action on tachykinin, working in human NK1-, NK2- and NK3the receptor or in their combinations

The invention relates to derivatives of 3-(piperidinyl-1)-chroman-5,7-diol and 1-(4-hydroxyphenyl)-2-(piperidinyl-1)alkanol General formula I or their pharmaceutically acceptable salts accession acid, in which (a) R2and R5taken individually and R1, R2, R3and R4independently represent hydrogen, (C1-C6)-alkyl, halogen, HE or or7and R5represents methyl; or (b) R2and R5taken together form a ring chroman-4-ol, a R1, R3and R4each independently represent hydrogen, (C1-C6)-alkyl, halogen, HE or or7; R7represents methyl; and R6represents a substituted piperidinyl or 8-azabicyclo[3,2,1]octenidine derived; provided that (a) if R2and R5taken separately, at least one of R1, R2, R3and R4is not hydrogen; and (b) if R2and R5taken together, at least one of R1, R3and R4is not hydrogen, with the property that the NMDA antagonist

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds represented by the general formula (I): and their pharmaceutically acceptable salts and esters possessing agonistic activity with respect to peroxisome proliferator receptors PPARα and/or PPARγ, to a pharmaceutical composition based on thereof and their using for preparing medicines wherein R1 means thiophenyl or phenyl optionally substituted with from one to three substitutes chosen independently from halogen atom, (C1-C8)-alkoxy-group, (C1-C8)-alkyl and (C1-C8)-alkyl substituted with one-three halogen atoms; R2 means hydrogen atom or (C1-C8)-alkyl; R3 means phenoxy-, (C2-C8)-alkenyloxy- or (C1-C8)-alkoxy-group; R4 means hydrogen atom or (C1-C8)-alkyl wherein one of substitutes R5 and R6 means compound of the formula and another one means hydrogen atom and wherein the bond between carbon atoms Ca and Cb means a carbon-carbon simple or double bond; R7 means hydrogen atom or (C1-C8)-alkyl; R8 means hydrogen atom or (C1-C8)-alkyl being any of A and A1 means nitrogen atom and another means oxygen or sulfur atom; n means 1, 2 or 3.

EFFECT: valuable medicinal properties of compound and pharmaceutical composition.

30 cl, 1 tbl, 14 sch, 86 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of benzimidazole of the general formula (I): wherein A represents -CH2- or -C(O)-; Y represents -S- or -NH-; R1 and R2 represent independently hydrogen atom, (C1-C8)-alkyl, (C5-C9)-bicycloalkyl optionally substituted with one or some similar or different (C1-C6)-alkyl radicals, or radical of the formula -(CH2)n-X wherein X represents amino-group, (C3-C7)-cycloalkyl and other values of radicals also given in the invention claim; R3 represents -(CH2)p-W-(CH2)p'-Z3 wherein W3 represents a covalent bond, -CH(O)- or -C(O)-; Z3 represents (C1-C6)-alkyl, aryl radical, heteroaryl and other values of radical also; V3 represents -O-, -S-, -C(O)-, -C(O)-O-, -SO2- or a covalent bond; Y3 represents (C1-C6)-alkyl radical optionally substituted with one or some halogen-radicals, amino-group, di-((C1-C6)-alkyl)-amino-group, phenylcarbonylmethyl, heterocycloalkyl or aryl radicals; p, p' and p'' represent independently a whole number from 0 to 4; R4 represents radical of the formula: -(CH2)s-R''4 wherein R''4 represents heterocycle comprising at least one nitrogen atom and optionally substituted with (C1-C6)-alkyl or aralkyl, and other values of radicals given in the invention claim also. Also, invention relates to a pharmaceutical composition showing antagonistic property with respect to GnRH and based on these compounds. Also, using above proposed compounds for preparing a medicament is considered. Invention provides synthesis of novel compounds, preparing pharmaceutical composition and medicament based on thereof in aims for treatment of such diseases as endometriosis, fibroma, polycystic ovary, breast, ovary and endometrium cancer, gonadotropic hypophysis desensitization in medicinal stimulation of ovary in fertility treatment in females.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

18 cl, 2 tbl, 538 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention describes a compound of the formula (I):

wherein R1 is chosen from the following group: (C1-C6)-alkyl, (C2-C6)-alkylidene, (C2-C6)-alkenyl, (C2-C6)-alkynyl, -O-(C1-C6)-alkyl, -O-(C2-C6)-alkenyl; m = 1; C3-C4 mean -CH2-CH or -CH=C, or C4 represents -CH and C3 absents; R2 and R3 represent hydrogen atom (H); or R2, R3, m and C3-C4 form compound of the formula:

; each among R4 and R5 is chosen independently from group comprising H, halogen atom, hydroxy-group, (C1-C6)-alkyl, -O-(C1-C6)-alkyl; L1 and L2 represent biradicals chosen from group comprising -(CR6)=C(R7), -C(R6)=N and -N=C(R6)-, -S-; Y is chosen from group consisting of oxygen atom (O) and two hydrogen atoms; X is chosen from group comprising -C(R6)(R7)-C(R6)(R7)-, -C(R6)=C(R7)-, -O-C(R6)(R7)-, -C(R6)(R7-O-, -S-C(R6)(R7)-, -C(R6)(R7)-S- and -S-. Invention describes compositions comprising compounds of the formula (I), method for enhancing activity of muscarinic receptors of subtype M1, method for treatment of diseases associated with muscarinic receptors.

EFFECT: valuable medicinal properties of compounds and composition.

14 cl, 2 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a compound of the formula (I): or its pharmaceutically acceptable salt wherein X is chosen from the group consisting of carbon (C), oxygen (O), nitrogen (N) and sulfur (S) atoms; Z represents nitrogen atom (N); Y is chosen from the group consisting of =O, =S or their tautomers; SPU means a spacer element providing distance d between Z and N atom wherein -SPU- represents bi-radical -(CR6R7)n- wherein n means 1, 2, 3, 4 or 5; N atom in common with R1 and R2 forms heterocyclic ring wherein indicated heterocyclic ring is chosen from the group consisting of piperidine and 8-azabicyclo[3.2.1]octane and wherein heterocyclic ring is substituted with one or more substitutes R4 chosen from the group consisting of hydrogen atom, (C1-C8)-alkyl, (C3-C8)-cycloalkyl, (C1-C8)-alkoxy-group, (C1-C8)-alkylidene, (C2-C8)-alkenyl, (C2-C8)-alkynyl, (C1-C6)-alkyloxyimino-group each of them is substituted optionally with a substitute R5 and wherein at least with one of indicated substitutes R4 is represented by R4' chosen from the group consisting of (C1-C8)-alkyl, (C3-C8)-cycloalkyl, (C1-C8)-alkoxy-group and (C1-C8)-alkylidene wherein each of them is substituted optionally with a substitute R5 wherein R5 is chosen from the group consisting of hydrogen, halogen atom, hydroxy-group, (C1-C8)-alkyl, (C1-C8)-alkoxy-group, (C3-C8)-cycloalkyl, (C2-C8)-alkenyl and (C2-C8)-alkynyl; RX can absent or can be chosen from the group consisting of hydrogen atom and optionally substituted (C1-C8)-alkyl; R3 can be represented in 0-4-fold range and chosen from the group consisting of halogen atom, optionally substituted (C1-C8)-alkyl and (C1-C8)-alkoxy-group; each R6 and R7 is chosen optionally and independently among the group consisting of hydrogen atom, hydroxy-group and optionally substituted (C-C8)-alkyl. Also, invention relates to a pharmaceutical composition possessing the selective activity with respect to M and/or M4-subtypes of muscarinic receptors and antagonism with respect to D2-dopamine receptors and comprising compound of the formula (I) by claim 1 in common with pharmaceutically acceptable carriers or excipients. Also, invention relates to a method for enhancing activity of cholinergic receptor comprising interaction of cholinergic receptor and system comprising cholinergic receptor with the effective amount of at least one compound of the formula (I) by claim 1. Also, invention relates to using the compound according to any claim among 1-11 or its pharmaceutically acceptable salt, or pharmaceutical composition containing any base for preparing a medicinal preparation used in prophylaxis aim or treatment of psychosis or for attenuation of symptoms associated with psychosis.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

27 cl, 3 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to new 2-arylimino-2,3-dihydrothiazole derivatives of formula described in claims having affinity and selectivity to somatostatin receptors and useful as drugs for treatment of pathological conditions or diseases mediated by one or more somatostatin receptors, such as acromegalia, chromophone adenoma, endocrine pancreatic tumor, argentaffinoma syndrome, gastrointestinal hemorrhage, etc.

EFFECT: new agent for treatment of pathological conditions or diseases mediated by somatostatin receptors.

6 cl, 2836 ex

FIELD: organic chemistry, chemical technology, pesticides.

SUBSTANCE: invention relates to a method for synthesis of compound of the formula (I): wherein Q means nitrogen atom (N); Y means nitro-group (-NO2); Z means -NR3; R1 and R2 mean in common alkylene bridge that comprises two or three carbon atoms and, optionally, a heteroatom chosen from the group comprising -NR5 and oxygen atom (O); R3 means unsubstituted (C1-C12)-alkyl; R5 means hydrogen atom (H) or (C1-C12)-alkyl. Method involves the following steps: (a) interaction of compound of the formula (II): wherein X means a leaving group with a halogenated agent to yield compound of the formula (III): wherein W means halogen atom and wherein treatment of compound of the formula (III) involves extraction of compound of the formula (III) with hydrochloric acid taken in the concentration 10-50 wt.-%, and (b) interaction of the synthesized compound of the formula (III) with compound of the formula (IV): wherein R1, R2, Y, Z and Q have above given values. In the process for synthesis of compound of the formula (III) the stage (a) involves purification stage wherein formed crude product is treated with water at acid range of pH values.

EFFECT: improved method of synthesis.

3 cl, 6 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention proposes compounds of the general formula (1): wherein X is chosen from sulfur atom and methylene group; X1 is chosen from sulfur atom and methylene group; X2 is chosen from oxygen (O), sulfur (S) atoms and methylene group; X3 means -NR5 or carbonyl group; R1 means hydrogen atom or nitrile group; R and R3 are chosen independently from hydrogen atom (H) and (C1-C6)-alkyl; R4 means R4A when X3 means -NR5 and R4B when X3 means carbonyl group; R4A is chosen from -R6R7NC(=O), -R6R7NC(=S), -R8(CH2)qC(=O), -R8(CH2)qC(=S), -R8(CH2)qSO2 and -R8(CH2)qOC(=O); R4B means -R6R7N; R5 means hydrogen atom (H); R6 and R7 are chosen independently from -R8(CH2)q, or they form in common -(CH2)2-Z1-(CH2)2- or -CHR9-X2-CH2-CHR10-; R8 is chosen from hydrogen atom (H), (C1-C4)-alkyl, cycloalkyl group condensed with benzene ring, acyl, dialkylcarbamoyl, dialkylamino-group, N-alkylpiperidyl, optionally substituted aryl, optionally substituted α-alkylbenzyl, optionally substituted aroyl, optionally substituted arylsulfonyl and optionally substituted heteroaryl representing monocyclic 5- and 6-membered ring aromatic group with one or two heteroatoms chosen from nitrogen, oxygen and sulfur atoms, and derivatives of abovementioned rings condensed with benzene; R9 and R10 are chosen independently from hydrogen atom (H), hydroxymethyl and cyanomethyl groups; Z1 is chosen from -(CH2)r-, -O-, and -N((CH2)q)R8)-; Z2 means optionally the substituted ortho-phenylene group; m = 1-3; n = 0-4; p = 2-5; q = 0-3, and r = 1 or 3. Proposed compounds are inhibitors of dipeptidyl-peptidase IV and can be used in preparing pharmaceutical compositions designated for treatment of different diseases, among them, diabetes mellitus of type 2.

EFFECT: valuable medicinal and biochemical properties of compounds and pharmaceutical composition.

22 cl, 8 tbl, 453 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to derivatives of piperidine of the general formula (I): in free form or as a salt wherein Ar1 means phenyl substituted with one or some halogen atoms; Ar2 means phenyl or naphthyl that can be unsubstituted or substituted with one or some substitutes chosen from the group comprising halogen atom, cyano-, hydroxy-, nitro-group, (C1-C8)-alkyl, (C1-C8)-halogenalkyl, (C1-C8)-alkoxy-group or (C1-C8)-alkoxycarbonyl; R1 means hydrogen atom or (C1-C8)-alkyl optionally substituted with hydroxy-,(C1-C8)-alkoxy-, acyloxy-group, -N(R2)R3, halogen atom, carboxy-group, (C1-C8)-alkoxycarbonyl, -CON(R4)R5 or monovalence cyclic organic group; each among R2 and R3 and independently of one another means hydrogen atom or (C1-C8)-alkyl, or R2 means hydrogen atom and R3 means acyl or -SO2R6, or R and R3 in common with nitrogen atom to which they are bound form 5- or 6-membered heterocyclic group; each among R4 and R5 and independently of one another means hydrogen atom or (C1-C8)-alkyl, or R4 and R in common with nitrogen atom to which they are bound form 5- or 6-membered heterocyclic group; R6 means (C1-C8)-alkyl, (C1-C8)-halogenalkyl or phenyl optionally substituted with (C1-C8)-alkyl; n means 1, 2, 3 or 4 under condition that when Ar1 means para-chlorophenyl and R1 means hydrogen atom then Ar2 doesn't mean phenyl or para-nitrophenyl. Compounds of the formula (I) possess the inhibitory CCR-3 activity and can be used in medicine.

EFFECT: improved preparing method, valuable medicinal properties of compounds.

7 cl, 47 ex

FIELD: organic chemistry, chemical technology, herbicides.

SUBSTANCE: invention describes new substituted derivatives of pyrazole of the general formula (I): wherein n = 0 or 1; group A represents independently hydrogen atom, alkyl group with 1-4 carbon atoms, halogenalkyl group with 1-4 carbon atoms, cycloalkyl group with 3-6 carbon atoms or phenyl group having substituting groups optionally; group D represents hydrogen atom, alkyl group with 1-4 carbon atoms, halogenalkyl group with 1-4 carbon atoms, alkenyl group with 2-4 carbon atoms, alkoxy-group with 1-4 carbon atoms, cycloalkyl group with 3-6 carbon atoms, halogen atom, alkoxycarbonyl group with 1-4 carbon atoms, alkylsulfonyl group with 1-4 carbon atoms or phenyl group; group E represents hydrogen atom, halogen atom or phenyl group; groups R1 and R2 both represent halogen atom; group R3 represents hydrogen atom, alkyl group with 1-4 carbon atoms, halogenalkyl group with 1-4 carbon atoms, alkenyl group with 2-4 carbon atoms, alkynyl group with 2-4 carbon atoms or benzyl group; groups R4 and R5 are similar or different and each represents hydrogen atom, alkyl group with 1-4 carbon atoms, halogenalkyl group with 1-4 carbon atoms, cycloalkyl group with 3-8 carbon atoms that can be substituted with alkyl group with 1-4 carbon atoms, alkenyl group with 2-4 carbon atoms, alkynyl group with 2-4 carbon atoms, cyanomethyl group or phenyl group; or each R4 and R5 group means benzyl group; or each R4 and R5 group represents α- or β-phenethyl group having substituting groups at benzyl ring optionally. Indicated substituting groups represent alkoxy-groups with 1-4 carbon atoms wherein indicated substituting groups substitute hydrogen atom at the arbitrary positions 0-2 of the benzyl ring; or groups R4 and R5 form in common 5-membered or 6-membered aliphatic ring wherein the indicated ring can be substituted with alkyl groups with 1-4 carbon atoms and indicated ring can comprise one or two heteroatoms chosen from nitrogen oxygen and sulfur atom, and a method for their preparing. Also, invention describes herbicide compositions based on compound of the formula (I). Invention provides preparing herbicide compositions showing the strong herbicide effect and broad herbicide spectrum of their effect.

EFFECT: improved preparing method, valuable properties of derivatives and compositions.

7 cl, 6 tbl, 3 ex

FIELD: organic chemistry, biochemistry, medicine.

SUBSTANCE: invention relates to a new biologically active compound of 4-oxoquinoline that is useful as an anti-HIV agent and to its pharmaceutically acceptable salt. Invention describes an anti-HIV agent comprising compound of 4-oxoquinoline represented by the following formula [I] or its pharmaceutically acceptable salt as an active component wherein ring Cy represents phenyl group, naphthyl group or pyridyl group and each this group is substituted optionally with 1-5 substituted chosen from the following group A wherein A represents the group consisting of cyano-group, phenyl group, nitro-group, halogen atom, (C1-C4)-alkyl group, halogen-(C1-C4)-alkyl group, halogen-(C1-C4)-alkoxy-group, -ORa1, -SRa1, -NRa1Ra2, -CONRa1Ra2, -SO2NRa1Ra2, -NRa1CORa3, -SO2Ra3, -NRa1SO2Ra3 and -COORa1 wherein Ra1 and Ra2 are similar or different and each represents hydrogen atom, (C1-C4)-alkyl group or benzyl group, and Ra3 represents (C1-C4)-alkyl group; R1 represent a substitute chosen from the following group B, or (C1-C10)-alkyl group optionally substituted with 1-3 substitutes chosen from halogen atom and the following group B wherein the group B represents the group consisting of phenyl group optionally substituted with phenyl group or 1-5 halogen atoms; (C3-C6)-cycloalkyl group, imidazolyl group, benzothiophenyl group, thiazolyl group optionally substituted with 1-3 (C1-C6)-alkyl groups, morpholinyl group, pyridyl group, -ORa4, -SRa4, -NRa4Ra5, -CONRa4Ra5, -SO2NRa4Ra5, -CORa6, -NRa4CORa6, -SO2Ra6, -NRa4SO2Ra6, -COORa4 and -NRa5COORa6 wherein Ra4 and Ra5 are similar or different and each represents hydrogen atom, (C1-C4)-alkyl group or phenyl group; Ra6 represents (C1-C4)-alkyl group; R2 represents hydrogen atom or (C1-C4)-alkyl group; R31 represents hydrogen atom, cyano-group, hydroxy-group, halogen atom or (C1-C4)-alkoxy-group; X represents -C-R32, and Y represents -C-R33 or nitrogen atom wherein R32 and R33 are similar or different and each represents hydrogen atom, cyano-group, halogen atom, pyrrolidinyl group, (C1-C10)-alkyl group optionally substituted with 1-3 halogen atoms, -ORa7, -SRa7, -NRa7Ra8, -NRa7CORa9, -COORa10 or -N=CH-NRa10Ra11 wherein Ra7 and Ra8 are similar or different and each represents hydrogen atom, phenyl group or (C1-C10)-alkyl group optionally substituted with (C3-C6)-cycloalkyl group or hydroxy-group; Ra9 represents (C1-C4)-alkyl group and Ra10 and Ra11 are similar or different and each represents hydrogen atom or (C1-C4)-alkyl group. Also, invention describes compound of the formula (III) given in the invention description, integrase inhibitor, antiviral agent, ant-HIV composition, anti-HIV agent, using compound of 4-oxoqionoline, method for inhibition of integrase activity, method for prophylaxis or treatment of viral infectious disease, pharmaceutical composition used for inhibition of integrase activity, antiviral composition and commercial package (variants). Invention provides the development of a pharmaceutical agent possessing inhibitory effect on activity of integrase.

EFFECT: valuable medicinal properties of compound, agent and composition.

40 cl, 7 tbl, 250 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to N3-alkylated benzimidazole derivatives for preparing a drug used in inhibition of MEK activity. Invention describes benzimidazole compound of the formula (I): and its pharmaceutically acceptable salts and solvates wherein R1, R2, R9 and R10 are chosen independently from hydrogen atom, halogen atom, trifluoromethyl group, difluoromethoxy-, trifluoromethoxy-, azido-group, -OR3, -C(O)R3, -C(O)OR3, -OC(O)R3, (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C3-C10)-cycloalkylalkyl wherein each alkyl and cycloalkyl moiety is substituted possibly with groups in the amount from one to five and chosen independently from halogen atom, trifluoromethyl group, difluoromethoxy-, trifluoromethoxy-group; R3 is chosen from hydrogen atom, trifluormethyl group, (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C3-C10)-cycloalkylalkyl wherein each alkyl and cycloalkyl group is substituted possibly with groups in the amount from one to five and chosen independently from halogen atom, trifluoromethyl group, difluoromethoxy-, trifluoromethoxy-group, -C(O)R', -C(O)OR', -OC(O)R' wherein R' is chosen independently from hydrogen atom, lower alkyl; R4 represents independently hydrogen atom or (C1-C6)-alkyl; R6 is chosen from trifluoromethyl group or (C1-C10)-alkyl, (C3-C10)-cycloalkyl wherein each alkyl and cycloalkyl moiety is substituted possibly with groups in the amount from one to five and chosen independently from halogen atom, trifluoromethyl group, difluoromethoxy-, trifluoromethoxy-group, -C(O)R', -C(O)OR', -OC(O)R', -OR'; R7 is chosen from (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C3-C10)-cycloalkylalkyl wherein each alkyl and cycloalkyl moiety is substituted possibly with groups in the amount from one to five and chosen independently from halogen atom, trifluoromethyl group, difluoromethoxy-, trifluoromethoxy-group, -C(O)R3, -C(O)OR3, -OC(O)R3, -SO2R6, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl; W is chosen from -C(O)OR3, -C(O)NR3R4, -C(O)NROR3, -C(O)R4OR3, -C(O)(C3-C10)-cycloalkyl, -C(O)(C1-C10)-alkyl. Also, invention describes compositions used for inhibition of MEK activity, using such compounds for preparing a drug used in inhibition of MEK activity and preparing a drug used in cancer treatment.

EFFECT: valuable medicinal and biochemical properties of compounds and composition.

17 cl, 10 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes novel compounds of the general formula (I) wherein p, R1, R2, R3 and A are determined in the invention description, their individual isomers and their pharmaceutically acceptable salts. Proposed compounds possess antagonistic effect with respect to muscarinic receptors that allows their using in treatment and prophylaxis of diseases yielding to treatment with muscarinic receptor antagonist. Also, invention describes a pharmaceutical composition containing these compounds.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

23 cl, 22 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds represented by the general formula (I): and their pharmaceutically acceptable salts and esters possessing agonistic activity with respect to peroxisome proliferator receptors PPARα and/or PPARγ, to a pharmaceutical composition based on thereof and their using for preparing medicines wherein R1 means thiophenyl or phenyl optionally substituted with from one to three substitutes chosen independently from halogen atom, (C1-C8)-alkoxy-group, (C1-C8)-alkyl and (C1-C8)-alkyl substituted with one-three halogen atoms; R2 means hydrogen atom or (C1-C8)-alkyl; R3 means phenoxy-, (C2-C8)-alkenyloxy- or (C1-C8)-alkoxy-group; R4 means hydrogen atom or (C1-C8)-alkyl wherein one of substitutes R5 and R6 means compound of the formula and another one means hydrogen atom and wherein the bond between carbon atoms Ca and Cb means a carbon-carbon simple or double bond; R7 means hydrogen atom or (C1-C8)-alkyl; R8 means hydrogen atom or (C1-C8)-alkyl being any of A and A1 means nitrogen atom and another means oxygen or sulfur atom; n means 1, 2 or 3.

EFFECT: valuable medicinal properties of compound and pharmaceutical composition.

30 cl, 1 tbl, 14 sch, 86 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention describes a compound of the formula (I):

wherein R1 is chosen from the following group: (C1-C6)-alkyl, (C2-C6)-alkylidene, (C2-C6)-alkenyl, (C2-C6)-alkynyl, -O-(C1-C6)-alkyl, -O-(C2-C6)-alkenyl; m = 1; C3-C4 mean -CH2-CH or -CH=C, or C4 represents -CH and C3 absents; R2 and R3 represent hydrogen atom (H); or R2, R3, m and C3-C4 form compound of the formula:

; each among R4 and R5 is chosen independently from group comprising H, halogen atom, hydroxy-group, (C1-C6)-alkyl, -O-(C1-C6)-alkyl; L1 and L2 represent biradicals chosen from group comprising -(CR6)=C(R7), -C(R6)=N and -N=C(R6)-, -S-; Y is chosen from group consisting of oxygen atom (O) and two hydrogen atoms; X is chosen from group comprising -C(R6)(R7)-C(R6)(R7)-, -C(R6)=C(R7)-, -O-C(R6)(R7)-, -C(R6)(R7-O-, -S-C(R6)(R7)-, -C(R6)(R7)-S- and -S-. Invention describes compositions comprising compounds of the formula (I), method for enhancing activity of muscarinic receptors of subtype M1, method for treatment of diseases associated with muscarinic receptors.

EFFECT: valuable medicinal properties of compounds and composition.

14 cl, 2 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention describes a method for synthesis of novel carboxylic acid amides of the general formula (I):

wherein R1 represents hydrogen atom (H); R2 represents a linear or branched (C1-C8)-alkyl possibly substituted with phenyl; or R1 and R2 in common with nitrogen atom (N) represent a 5-membered heterocyclic residue or a 6-membered heterocyclic residue comprising oxygen atom additionally; n = 0, 1. Method involves heating a mixture of 5-amino-1,2,4-triazol-3-ylcarboxylic acid ester of the general formula (II):

wherein R3 represents (C1-C4)-alkyl group; n = 0, 1, amine of the general formula (III):

wherein R1 and R2 have value given above and tertiary aliphatic amine of the formula (IV) given in the invention description at temperature 70-130°C wherein components are taken in the ratio (II) : (III) : (IV) = 1.0:(1.1-2.5):(1.0-3.0), respectively. Method provides decreasing the cost of compounds of the formula (I) based on using the more inexpensive raw, reducing duration of the process and enhancing safety of the process. Synthesized compounds can be used in synthesis of biologically active substances and dyes.

EFFECT: improved method of synthesis, valuable properties of compounds.

2 cl, 6 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a compound of the formula (I): or its pharmaceutically acceptable salt wherein X is chosen from the group consisting of carbon (C), oxygen (O), nitrogen (N) and sulfur (S) atoms; Z represents nitrogen atom (N); Y is chosen from the group consisting of =O, =S or their tautomers; SPU means a spacer element providing distance d between Z and N atom wherein -SPU- represents bi-radical -(CR6R7)n- wherein n means 1, 2, 3, 4 or 5; N atom in common with R1 and R2 forms heterocyclic ring wherein indicated heterocyclic ring is chosen from the group consisting of piperidine and 8-azabicyclo[3.2.1]octane and wherein heterocyclic ring is substituted with one or more substitutes R4 chosen from the group consisting of hydrogen atom, (C1-C8)-alkyl, (C3-C8)-cycloalkyl, (C1-C8)-alkoxy-group, (C1-C8)-alkylidene, (C2-C8)-alkenyl, (C2-C8)-alkynyl, (C1-C6)-alkyloxyimino-group each of them is substituted optionally with a substitute R5 and wherein at least with one of indicated substitutes R4 is represented by R4' chosen from the group consisting of (C1-C8)-alkyl, (C3-C8)-cycloalkyl, (C1-C8)-alkoxy-group and (C1-C8)-alkylidene wherein each of them is substituted optionally with a substitute R5 wherein R5 is chosen from the group consisting of hydrogen, halogen atom, hydroxy-group, (C1-C8)-alkyl, (C1-C8)-alkoxy-group, (C3-C8)-cycloalkyl, (C2-C8)-alkenyl and (C2-C8)-alkynyl; RX can absent or can be chosen from the group consisting of hydrogen atom and optionally substituted (C1-C8)-alkyl; R3 can be represented in 0-4-fold range and chosen from the group consisting of halogen atom, optionally substituted (C1-C8)-alkyl and (C1-C8)-alkoxy-group; each R6 and R7 is chosen optionally and independently among the group consisting of hydrogen atom, hydroxy-group and optionally substituted (C-C8)-alkyl. Also, invention relates to a pharmaceutical composition possessing the selective activity with respect to M and/or M4-subtypes of muscarinic receptors and antagonism with respect to D2-dopamine receptors and comprising compound of the formula (I) by claim 1 in common with pharmaceutically acceptable carriers or excipients. Also, invention relates to a method for enhancing activity of cholinergic receptor comprising interaction of cholinergic receptor and system comprising cholinergic receptor with the effective amount of at least one compound of the formula (I) by claim 1. Also, invention relates to using the compound according to any claim among 1-11 or its pharmaceutically acceptable salt, or pharmaceutical composition containing any base for preparing a medicinal preparation used in prophylaxis aim or treatment of psychosis or for attenuation of symptoms associated with psychosis.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

27 cl, 3 ex

FIELD: organic chemistry, biochemistry, medicine.

SUBSTANCE: invention relates to novel derivatives of imidazolidine and describes compound of the formula (I): wherein R1 is chosen from the group consisting of (C1-C9)-alkyl, (C1-C2)-alkyl-Ar; R2 is chosen from the group consisting of phenyl, (C1-C4)-alkyl-Ar', -NC(O)R4, (C2-C4)-alkyl-NR3R4, (C1-C3)-alkyl-C(O)-Ar'; R3 is chosen from the group consisting of hydrogen atom (H), (C1-C2)-alkyl-Ar and Ar; R4 represents R3, or R4 can be taken in common with R3 and nitrogen atom to which they are bound for formation of morpholinyl; Ar is chosen from the group consisting of phenyl that can be optionally substituted with one, two or three substitutes chosen from the group consisting of F, Cl, Br and J; Ar' is chosen from the group consisting of phenyl, biphenyl, benzofuranyl and benz[b]thiophene that can be optionally substituted with one, two or three substitutes chosen from the group consisting of (C1-C6)-alkyl, -(CH2)0-5CO2R1, F, Cl, Br, J and COOH; A is chosen from -C(O)NHOH or -N(CHO)OH; X means -NH if Y means -C(O), or its pharmaceutically acceptable salt. Also, invention describes a method for treatment of bacterial infection based on compounds of the formula (I). Invention provides preparing novel compounds possessing the useful biological properties.

EFFECT: valuable medicinal and biochemical properties of compounds.

4 cl, 3 ex

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