Piperazine derivatives that destabilize androgen receptors

Abstract

This invention relates to new piperazine derivatives of general formula I, 1

Description

[0002] This invention relates to substituted piperazine derivatives that destabilize the androgen receptor (AR), and process for the production of these piperazine derivatives, their intermediate products as well as pharmaceutical preparations that contain the piperazine derivatives according to the invention and their use for the production of pharmaceutical agents.

[0003] In industrialized countries, prostate cancer, behind lung cancer, is the second main cause of death by cancer in men. In men over 55 years of age, 4% of deaths are attributed to a prostate tumor disease, and it is suggested that the proportion in men over 80 increases up to 80% of deaths. The mortality rate is still always relatively low, but it increases annually to about 14%. The number of men in whom a prostate tumor was diagnosed increased in recent years by 30%, which can be attributed, however, less to an increasing number of new diseases but rather to that the population is generally older, that the diagnostic processes have improved and that systematic screening programs were introduced (E. J. Small, D. M. Reese, Curr. Opi. Oncol. 2000, 12, 265-272).

[0004] The prostate tumor grows in an androgen-dependent manner in the early stages. As long as the tumor is limited locally to the prostate, it can be treated removed by surgical intervention or by radiation therapy, whereby these methods are associated with corresponding risks. In the cases in which the tumor is no longer locally limited, and has already formed metastases, the tumor is treated in a palliative manner by reduction of the testosterone level in the blood. This is carried out either surgically by castration or medicinally by treatment with antiandrogens (bicalutamide, cyproterone acetate, flutamide), LHRH agonists (buserelin, zoladex), LHRH antagonists (cetrorelix) or 5α-reductase inhibitors (finasteride). Since the adrenal androgen synthesis remains unaffected in surgical castration, more recently a combined surgical and medicinal treatment is frequently performed. This treatment, however, has only temporary success, since renewed growth of the tumor generally occurs after two years at the latest, and said renewed growth in most cases is then hormone-independent (L. J. Denis, K. Griffith, Semin. in Surg. Onc. 2000, 18, 52-74). Up until now despite intensive research in the last 50 years, there has been no effective treatment against these advanced stages. The 5-year survival rate in these patients is under 15%.

[0005] There are various indications that show that the androgen receptor plays an important role in the development and the growth of the prostate tumor not only in the early hormone-dependent stages but also in late hormone-independent stages of the tumor progression.

[0006] The androgen receptor belongs to the family of steroid hormone receptors that act as transcription factors. The androgen receptor binds androgens, by which it is stabilized and protected from a quick proteolytic degradation. After hormone binding, it is transported into the nucleus where it activates certain genes by binding to so-called androgen-responsive DNA elements that are in promoter regions (D. J. Lamb et al., Vitam. Horm. 2001, 62, 199-230).

[0007] Studies on prostate tumors show that an amplification of the androgen receptor locus was detected in 30% of the advanced tumors. In other cases, a number of mutations were found in the androgen receptor gene that are located in various domains of the androgen receptor molecule and result in altered receptor properties. Mutated receptors can have either a higher affinity for androgens, can be constitutively active, can change their ligand specificity, such that they are activated by other steroid hormones or even antiandrogens, can be activated via interactions with molecules from other growth-promoting signal-transmission methods, which change interaction with co-factors, or can activate other target genes (J. P. Elo, T. Visakorpi, Ann. Med. 2001, 33, 130-41).

[0008] The identification of antiandrogens that inhibit not only the natural androgen receptor but also its mutated forms and in addition change the receptor molecule so that it is destabilized, would presumably be very helpful in treating prostate tumors in various stages. Such compounds could prevent a recurrence of tumor growth or at least considerably delay such recurrence. In the case of the estrogen receptor, ligands could be identified that destabilize the receptor and result in a reduction of the receptor content in vitro and in vivo (S. Dauvois et al. Proc. Natl. Acad. Sci. USA 1992, 89, 4037-41; R. A. McClelland et al. Eur. J. Cancer 1996, 32A, 413-6).

[0009] Nonsteroidal antiandrogens are described in U.S. Pat. No. 5,411,981 (phenylimidazolidine derivatives), in WO97/00071 (specifically substituted phenyldimethylhydantoins as well as imino or thione derivatives thereof), in WO00/37430 (phenylalanines, phenylhydantoins as well as phenylureas), in WO01/58855 (aminopropanilides) and in EP1122242 (substituted cyanophenylpiperazines).

[0010] The object of this invention consists in making available compounds with antiandrogenic action that destabilize the androgen receptor, inhibit the prostate tumor growth and simultaneously have a high, optionally oral bioavailability.

[0011] Studies with nonsteroidal antiandrogens have shown that they have advantages compared to the steroidal compounds and therefore are to be preferred. Thus with nonsteroidal compounds, a more selective action can be achieved with fewer adverse side effects. In contrast to the steroidal antiandrogens, e.g., the progestagenic activity is lacking in the known nonsteroids bicalutamide and flutamide, and in addition, their use results in an increase in the testosterone level in the serum, which clinically could result in preserving potency.

[0012] This object is achieved according to the invention by the new compounds of general formula I:

[0013] This invention relates to compounds of general formula I, whereby 2

[0014] V stands for a substituted, aromatic radical of general formula II, 3

[0015] in which

[0016] A stands for an acetyl group, an acetylamino group, a cyano group, a nitro group, a trifluoromethyl group, or a halogen (fluorine, chlorine),

[0017] B stands for a hydrogen atom, a halogen (fluorine, chlorine) or a trifluoromethyl group, or

[0018] A and B together stand for a cyclic group of formula III or IV that is bonded to the aromatic ring, whereby E stands for a methylene group or an oxygen atom, 4

[0019] W stands for a heterocyclic compound of formula V, 5

[0020] in which

[0021] T can represent carbon or nitrogen,

[0022] if T stands for carbon, a double bond is to be present between Q and T, and Q means a group ═C(CH3)— and U means oxygen, and n is to assume one of the integral values 1, 2, 3, 4, 5, 6, 7, or 8, or

[0023] if T stands for nitrogen, a single bond is to be present between Q and T, and Q means a group —C(CH3)2— and U means sulfur, and n is to assume one of the integral values 2, 3, 4, 5, 6, 7, or 8,

[0024] i and j, independently of one another, stand for the values 1 and 2, whereby i+j can assume the value 2 or 3,

[0025] R and R′, independently of one another, can be a hydrogen atom or a methyl group,

[0026] Y stands for a bond between the heterocyclic nitrogen and Z, for a carbonyl group —C(O)—, for a sulfonyl group —S(O)2—, for an iminocarbonyl group —C(O)N(Z′)-, for an iminosulfonyl group —S(O)2N(Z′)-, for an imino(thioxomethyl) group —C(S)N(Z′)-, for an oxycarbonyl-imino(thioxomethyl) group —C(S)N(Z′)C(O)O—, for an oxycarbonyl group —C(O)O—, for a sulfanylcarbonyl group —C(O)S—, and

[0027] Z and Z′, independently of one another, stand for an unbranched C1-C8-alkyl group or branched C3-C8-alkyl group, a C3-C6-cycloalkyl group that is optionally substituted with a phenyl radical, a (C3-C6-cycloalkyl)-C1-C4-alkylene group, a branched or unbranched C2-C5-alkenyl group, a branched or unbranched C2-C5-alkenyl group, a C3-C5-alkinyl group, a C1-C4-alkoxy group, cyano group, phenylsulfanyl group or hydroxy-C1-C4-alkylene group, a (2-methoxyethoxy)methyl group, a [2-(2-methoxyethoxy)ethoxy]methyl group, a 2-(2-methoxyethoxy)ethyl group, a 2-[2-(2-methoxyethoxy)ethoxy] ethyl group, a C1-C4-alkoxy-C1-C4-alkylene group, a C1l-C4-alkoxycarbonyl-C1-C4-alkylene group, an adamantyl group, a trichloroacetyl group; an aryl, heteroaryl, heterocyclyl, aryl-C1-C4-alkylene, heteroaryl-C1-C4-alkylene, aryloxy-C1-C4-alkylene, heteroaryloxy-C1-C4-alkylene, aryl-C1-C4-alkylenoxy-C1-C4-alkylene group that is unsubstituted or that is substituted with up to three branched or unbranched C1-C4-alkyl, C2-C6-alkenyl, C3-C6-cycloalkyl, C3-C6-cycloalkyloxy, phenyl, cyano, halogen, methoxy, ethoxy, phenoxy, benzyloxy, methylsulfanyl, ethylsulfanyl, benzylsulfanyl, phenylsulfanyl, dimethylamino, acetylamino, trifluoromethyl, trifluoromethoxy, trifluoromethylsulfanyl, acetyl, (1-iminoethyl) or nitro groups, or a radical of formula CpFqHr with p=1, 2, 3, 4, q>1 and q+r=2p+1, and

[0028] Z′ in addition to the above-mentioned definitions stands for a hydrogen atom.

[0029] The compounds according to the invention are distinguished in that in each case they contain a diazacycloalkane nucleus whose nitrogen atoms are presented in substituted form in each case.

[0030] The unbranched C1-C8-alkyl groups for radicals Z and Z′ can be, for example, a methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl or n-octyl group; the branched C3-C8-alkyl groups are an iso-propyl, iso-butyl, sec-butyl, tert-butyl, iso-pentyl, neo-pentyl, 2-methylpentyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 2-methylhexyl, 2,2-dimethylpentyl, 2,2,3-trimethylbutyl or 2,3,3-trimethylbutyl group.

[0031] The C3-C6-cycloalkyl groups that are optionally substituted with a phenyl radical for radicals Z and Z′ can readily be a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or phenylcyclopropyl group, phenylcyclobutyl, phenylcyclopentyl, or phenylcyclohexyl group.

[0032] The (C3-C6-cycloalkyl)-C1-C4-alkylene groups for radicals Z and Z′ can be, for example, a cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyclopropylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl, cyclopropylpropyl, cyclobutylpropyl, cyclopentylpropyl, cyclohexylpropyl, cyclopropylbutyl, cyclobutylbutyl, cyclopentylbutyl or cyclohexylbutyl group.

[0033] The branched or unbranched C2-C5-alkenyl groups for the radicals Z and Z′ can be, for example, a vinyl, allyl, homoallyl, (E)-but-2-enyl, (Z)-but-2-enyl, (E)-but-1-enyl, (Z)-but-1-enyl, pent-4-enyl, (E)-pent-3-enyl, (Z)-pent-3-enyl, (E)-pent-2-enyl, (Z)-pent-2-enyl, (E)-pent-1-enyl, (Z)-pent-1-enyl, 2-methylvinyl, 3-methylbut-3-enyl, 2-methylbut-3-enyl, (E)-2-methylbut-2-enyl, (Z)-2-methylbut-2-enyl, or 3-methylbut-2-enyl group.

[0034] The C3-C5-alkinyl groups for radicals Z and Z′ can be, for example, a prop-1-inyl, prop-2-inyl, but-1-inyl, but-2-inyl, but-3-inyl, pent-1-inyl, penty-2-inyl, pent-3-inyl, pent-4-inyl, 1-methylprop-2-inyl, 1-methylbut-3-inyl, or 1-ethylprop-2-inyl group.

[0035] The C1-C4-alkoxy groups for radicals Z and Z′ can be, for example, a methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, sec-butoxy, iso-butoxy or tert-butoxy group.

[0036] The C1-C4-alkylene groups within radicals Z and Z′ can be, for example, a methylene group (—CH2—), ethylidene group [—CH(CH3)—], ethylene group (—CH2CH2—), 1,3-propylene group (—CH2CH2CH2—), 1,2-propylene group [—CH2CH(CH3)—], 1,4-butylene group (—CH2CH2CH2CH2—), 1,3-butylene group [—CH2CH2CH(CH3)—], 1,2-butylene group [—CH2CH(CH2CH3)—], 2-methyl-1,2-propylene group [—CH2C(CH3)2—], or 2-methyl-1,3-propylene group [—CH2CH(CH3)CH2—].

[0037] The hydroxy-C1-C4-alkylene groups for radicals Z and Z′ can be a hydroxymethyl group (HOCH2—), 2-hydroxyethyl group (HOCH2CH2—), 1-hydroxyethyl group [CH3CH(OH)—], 3-hydroxypropyl group (HOCH2CH2CH2—), 2-hydroxypropyl group [CH3CH(OH)CH2CH2—], 1-hydroxypropyl group [CH3CH2CH(OH)—], 4-hydroxybutyl group (HOCH2CH2CH2CH2—), 3-hydroxybutyl group [CH3CH(OH)CH2CH2—], 2-hydroxybutyl group [CH3CH2CH(OH)CH2—], 1-hydroxybutyl group [CH3CH2CH2CH(OH)—], 1-hydroxy-1-methylethyl group [(CH3)2C(OH)—], or 1-hydroxy 1-methylpropyl group [CH3CH2C(CH3)(OH)—].

[0038] The C1-C4-alkoxycarbonyl-C1-C4-alkylene groups for radicals Z and Z′ are, for example, a combination of the C1-C4-alkoxycarbonyl group and the C1-C4-alkylene group. A C1-C4-alkoxycarbonyl group is defined as methoxycarbonyl-[MeOC(O)-], ethoxycarbonyl [EtOC(O)-), n-propoxycarbonyl-[CH3CH2CH2OC(O)-—], iso-propoxycarbonyl-[(CH3)2CHOC(O)—], n-butoxycarbonyl-[CH3CH2CH2CH2OC(O)—], iso-butoxycarbonyl-[(CH3)2CHCH2OC(O)—], sec-butoxycarbonyl-[CH3CH2(CH3)CHOC(O)—], tert-butoxycarbonyl [(CH3)3COC(O)—]. A C1-C4-alkylene group is defined as the C1-C4-alkylene groups that are further mentioned above. For example, the following radicals can be produced from the combination of these groups to form the C1-C4-alkoxycarbonyl-C1-C4-alkylene groups: (methoxycarbonyl)methyl-[CH3OC(O)CH2—], (ethoxycarbonyl)methyl-[CH3CH2OC(O)CH2—], (n-propoxycarbonyl)methyl-[CH3CH2CH2OC(O)CH2—], (iso-propoxycarbonyl)methyl-[(CH3)2CHOC(O)CH2—], (n-butoxycarbonyl)methyl-[CH3CH2CH2CH2OC(O)CH2—], (iso-butoxycarbonyl)methyl-[(CH3)2CHCH2OC(O)CH2—], (sec-butoxycarbonyl)methyl-[CH3CH2(CH3)CHOC(O)CH2—], (tert-butoxycarbonyl)methyl-[(CH3)3COC(O)CH2—], 2-(methoxycarbonyl)ethyl-[CH3OC(O)CH2CH2—], 2-(ethoxycarbonyl)ethyl-[CH3CH2OC(O)CH2CH2—], 2-(n-propoxycarbonyl)ethyl-[CH3CH2CH2OC(O)CH2CH2—], 2-(iso-propoxycarbonyl)ethyl-[(CH3)2CHOC(O)CH2CH2—], 2-(n-butoxycarbonyl)ethyl-[CH3CH2CH2CH2OC(O)CH2CH2—], 2-(iso-butoxycarbonyl)ethyl-[(CH3)2CHCH2OC(O)CH2CH2—], 2-(sec-butoxycarbonyl)-ethyl-[CH3CH2(CH3)CHOC(O)CH2CH2—], 2-(tert-butoxycarbonyl)ethyl-[(CH3)3COC(O)CH2CH2—].

[0039] The aryl groups for radicals Z and Z′ can be a phenyl, naphthalen-1-yl, naphthalen-2-yl, [1,1′-biphenyl]-2-yl, [1,1′-biphenyl]-3-yl or a [1,1′-biphenyl]-4-yl group.

[0040] The heteroaryl groups for radicals Z and Z′ can be a pyridinyl, pyrimidinyl, quinolinyl, isoquinolinyl, benzofuranyl, benzothienyl, 1,3-benzodioxolyl, 2,1,3-benzothiadiazolyl, indolyl, furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, pyrrolyl, pyrazolyl or an imidazolyl group that is linked via one of the sites that can be substituted.

[0041] The heterocyclyl groups for radicals Z and Z′ can be piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, tetrahydrofuranyl, tetrahydrothienyl, imidazolidinyl or a pyrrolidinyl group that is linked via one of the sites that can be substituted.

[0042] The substituents of the aryl, heteroaryl and heterocyclyl radicals, also in each case within the aryl-C1-C4-alkylene, heteroaryl-C1-C4-alkylene, aryloxy-C1-C4-alkylene, heteroaryl-oxy-C1-C4-alkylene, aryl-C1-C4-alkylenoxy-C1-C4-alkylene units for radical Z, can be, i.a.,

[0043] Unbranched or branched C1-C4-alkyl groups (methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, as well as tert-butyl-) and/or C2-C6-alkenyl groups (vinyl, allyl, homoallyl, (E)-but-2-enyl, (Z)-but-2-enyl, pent-4-enyl, (E)-pent-3-enyl, (Z)-pent-3-enyl, (E)-pent-2-enyl, (Z)-pent-2-enyl, 2-methylvinyl, 3-methylbut-3-enyl, 2-methylbut-3-enyl, (E)-2-methylbut-2-enyl, (Z)-2-methylbut-2-enyl, 2-ethylprop-2-enyl, hex-5-enyl, (E)-hex-4-enyl, (Z)-hex-4-enyl, (E)-hex-3-enyl, (Z)-hex-3-enyl, (E)-hex-2-enyl, (Z)-hex-2-enyl, 1-methylpent-4-enyl, (E)-1-methylpent-3-enyl, (Z)-1-methylpent-3-enyl, 1-ethylbut-3-enyl, (E)-1-methylpent-2-enyl, (Z)-1-methylpent-2-enyl) and/or C3-C6-cycloalkyl groups (cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl) and/or halogen (fluorine, chlorine, bromine, iodine).

[0044] The aryl-C1-C4-alkylene groups for radicals Z and Z′ can be a combination of the above-defined aryl and C1-C4-alkyl groups, for example: a phenylmethyl, 1-phenylethyl, 2-phenylethyl, 1-methyl-1-phenylethyl, 3-phenylpropyl-4-phenylbutyl, (naphthalen-1-yl)methyl, 1-(naphthalen-1-yl)ethyl, 2-(naphthalen-1-yl)-ethyl, (naphthalen-2-yl)methyl, 1-(naphthalen-2-yl)ethyl, 2-(naphthalen-2-yl)ethyl, ([1,1′-biphenyl]-2-yl)methyl, ([1,1′-biphenyl]-3-yl)methyl or a ([1,1′-biphenyl]-4-yl)methyl group.

[0045] The heteroaryl-C1-C4-alkylene groups for radicals Z and Z′ can be a combination of the above-defined heteroaryl and C1-C4-alkylene groups, for example a (pyridin-2-yl)methyl, (pyridin-3-yl)methyl, (pyridin-4-yl)methyl, (furan-2-yl)methyl, (furan-3-yl)methyl, (thien-2-yl)methyl, (thien-3-yl)methyl, 2-(thien-2-yl)ethyl or a 2-(thien-3-yl)ethyl group.

[0046] The aryloxy-C1-C4-alkylene groups for radicals Z and Z′ can be a combined linkage of the above-defined aryl and C1-C4-alkylene groups via an ether group (—O—), for example: a phenoxymethyl, 1-phenoxyethyl, 2-phenoxyethyl, 1-methyl-1-phenoxyethyl, 3-phenoxypropyl, 4-phenoxybutyl, [(naphthalen-1-yl)oxy]methyl, 1-[(naphthalen-1-yl)oxy]ethyl, 2-[(naphthalen-1-yl)oxy]-ethyl, [(naphthalen-2-yl)oxy]methyl, 1-[(naphthalen-2-yl)oxy]ethyl, 2-[(naphthalen-2-yl)-oxy]ethyl, [([1,1′-biphenyl]-2-yl)oxy]methyl, [([1,1′-biphenyl]-3-yl)oxy]methyl or a [([1,1′-biphenyl]-4-yl)oxy]methyl group.

[0047] The heteroaryloxy-C1-C4-alkylene groups for radicals Z and Z′ can be a combined linkage of the previously defined heteroaryl and C1-C4-alkylene groups via an ether group (—O—), for example: a [(pyridin-2-yl)oxy]methyl, [(pyridin-3-yl)oxy]methyl or a [(pyridin-4-yl)oxy]methyl group.

[0048] The aryl-C1-C4-alkylenoxy-C1-C4-alkylene groups for radicals Z and Z′ can be a sequentially combined linkage of the above-defined aryl and C1-C4-alkylene groups via an ether group (—O—) to the alkylene group, for example: a (phenylmethoxy)methyl group or a 2-(phenylmethoxy)ethyl group.

[0049] The radical of formula CpFqHr with p=1, 2, 3, 4, q>1 and q+r=2p+1 for the radical Z can be a trifluoromethyl, pentafluoroethyl, perfluoropropyl, perfluorobutyl or a 2,2,2-trifluoroethyl group.

[0050] Preferred according to this invention are those compounds of general formula I, in which: 6

[0051] A stands for a cyano group,

[0052] B stands for a trifluoromethyl group, or

[0053] AB together stand for a cyclic group of formula IIIa that is bonded to the aromatic ring, 7

[0054] n stands for one of the integral values 1 (only for the case that T represents carbon), 2, 3, 4, 5, 6, 7 or 8,

[0055] i and j stand for the value 1,

[0056] R and R′ stand for a hydrogen atom,

[0057] Y stands for a carbonyl group —C(O)—, for a sulfonyl group —S(O)2—, for an iminocarbonyl group —C(O)N(Z′)-, for an iminosulfonyl group —S(O)2 N(Z′), for an imino(thioxomethyl) group —C(S)N(Z′), for an oxycarbonylimino(thioxomethyl) group —C(S)N(Z′)C(O)O—, for an oxycarbonyl group —C(O)O—, for a sulfanylcarbonyl group —C(O)S—, and

[0058] Z and Z′, independently of one another, stand for an unbranched C1-C4-alkyl group or branched C3-C4-alkyl group, a C3-C6-cycloalkyl group that is optionally substituted for one with a phenyl radical, a (C3-C6-cycloalkyl)-C1-C4-alkylene group, a branched or unbranched C2-C3-alkenyl group, a C1-C4-alkoxy, cyano, phenylsulfanyl, or hydroxy-C1-C4-alkylene group, a (2-methoxyethoxy)methyl group, a [2-(2-methoxyethoxy)-ethoxy]methyl group, a 2-(2-methoxyethoxy)ethyl group, a 2-[2-(2-methoxyethoxy)ethoxy]ethyl group, a C1-C4-alkoxy-C1-C4-alkylene group, a C1-C4-alkoxycarbonyl-C1-C4-alkylene group; an aryl, heteroaryl, heterocyclyl, aryl-C1-C4-alkylene, heteroaryl-C1-C4-alkylene, aryloxy-C1-C4-alkylene, heteroaryloxy-C1-C4-alkylene, aryl-C1-C4-alkylenoxy-C1-C4-alkylene group that is unsubstituted or that is substituted with up to three branched or unbranched C1-C4-alkyl, C2-C4-alkenyl, C3-C6-cylcoalkyl, C3-C6-cycloalkyloxy, phenyl, cyano, halogen, methoxy, ethoxy, phenoxy, benzyloxy, methylsulfanyl, ethylsulfanyl, benzyl, sulfanyl, phenylsulfanyl, dimethylamino, acetylamino, trifluoromethyl, trifluoromethoxy, trifluoromethylsulfanyl, or acetyl groups, or a radical of formula CpFqHr with p=1, 2, 3, 4, q>1 and q+r=2p+1, and

[0059] Z′ in addition to the above-mentioned definitions stands for a hydrogen atom.

[0060] For the formation of pharmaceutically compatible salts of the compounds of general formula I according to the invention, according to the methods that are known to one skilled in the art, i.a., hydrochloric acid, hydrobromic acid, sulfuric acid and phosphoric acid, and nitric acid are considered as inorganic acids; i.a., acetic acid, propionic acid, hexanoic acid, octanoic acid, decanoic acid, oleic acid, stearic acid, maleic acid, fumaric acid, succinic acid, benzoic acid, ascorbic acid, oxalic acid, salicylic acid, tartaric acid, citric acid, lactic acid, glycolic acid, malic acid, mandelic acid, cinnamic acid, glutaminic acid, and aspartic acid are considered as carboxylic acids, and, i.a., methanesulfonic acid, ethanesulfonic acid, toluenesulfonic acid, benzenesulfonic acid as well as naphthalenesulfonic acid are considered as sulfonic acids.

[0061] The compounds of Examples 1 to 745 that are mentioned below according to the invention are especially preferred.

[0062] Pharmacological Studies

[0063] The compounds according to the invention were tested in various models. The compounds of general formula I according to the invention are distinguished in that in this case, these are compounds with antiandrogenic action that destabilize the androgen receptor, inhibit the prostate tumor growth and simultaneously have a high, optionally oral bio-availability.

[0064] The in-vitro tests regarding the influences on the activities of the androgen receptor were performed as follows:

[0065] In the diagrams presented here, the following abbreviations were used:

Bicalutamide: N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-
              fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide
R1881:        Methyltrienolone, 17β-hydroxy-17α-methylestra-4,9,11-
              trien-3-one
CPA:          Cyproterone acetate, 17-(acetyloxy)-6-chloro-1β,2β-
              dihydro-3′H-cyclopropa[1,2]pregna-1,4,6-triene-3,20-
              dione
Compound B:   4-[2,5-Dihydro-3-methyl-4-[4-[4-(methyl-
              sulfonyl)piperazin-1-yl]butyl]-2,5-dioxo-1H-pyrrol-1-yl]-
              2-(trifluoromethyl)benzonitrile (Example 117)

[0066] Model 1: Destabilization of the AR in LNCaP Cells by Test Substances

[0067] In a 25 cm2 cell culture flask, 2*106 LNCaP cells in 6 ml of RPMI 1640 without phenol red are grown with 4 mmol of glutamine and 5% activated-carbon-treated serum (CCS) and are cultivated overnight at 37° C., 5% CO2, in a moist atmosphere. On the next day, the cells are treated with the test substance at a concentration of 10 or 1 μm, whereby the final concentration of the solvent is 0.5% DMSO. As a control, cells are treated only with 0.5% DMSO. After an incubation time of 24 hours, the medium is changed with a renewed addition of substance and another 24 hours of incubation. After 48 hours, the cells are washed with PBS, dissolved with PBS/20 mmol of EDTA, washed again with PBS-CA2+/Mg2+ and then frozen for at least two hours as cell pellets at −80° C. Then, the cell pellet is resuspended in 200 μl of lysis buffer (50 mmol of tris/HCl, pH 7.5; 150 mmol of NaCl, 1.5 mmol of MgCl2, 0.2% SDS, 10% glycerol, 1 mmol of DTT, 0.01× complete-EDTA protease inhibitors (Roche, Mannheim)) and treated with 10U benzonase (Merck, Darmstadt) for 10 minutes at 4° C. After 5 mmol of EDTA is added, insoluble material is pelletized, and 25 μg of the cell extract is separated in a 4-12% SDS-polyacrylamide gel (Invitrogen). Then, the proteins are transferred to nitrocellulose (HyBondECL, Amersham) and incubated with monoclonal antibodies against the androgen receptor (AR441; Santa Cruz Biotechnologies; 1:400 dilution) and actin (ICN, 1:5000-1:20,000 dilution). After incubation with the secondary antibodies (anti-mouse IgG-HRP, Amersham or—AP, Invitrogen), the Western blot is developed by chemiluminescence (ECL, Amersham; Western Breeze, Invitrogen), and the light signals are quantified with a ChemiImager™ (Kodak). The amount of androgen receptor is calculated in a ratio to actin as a percentage of the DMSO control.

[0068] Table 1 shows the action of selected test substances at concentrations of 10 or 1 μM on the content of androgen receptor protein in the human prostate cell line LNCaP. The data correspond to the proportion by percentage of the AR content of cells that were treated only with the solvent DMSO (=control). The treatment of the cells with the cited test substances results in a treatment concentration of 10 μM in a reduction of the AR content to one-fifth of the control (22% of Example 248: 4-[2,5-dihydro-3-[6-[4-(2-methoxybenzoyl)piperazin-1-yl]hexyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile). The comparison substance bicalutamide does not influence the AR content, while the synthetic androgen R1881 stabilizes the AR protein. The latter is known from the literature (J. A. Kemppainen et al. J. Biol. Chem. 1992, 267, 968-974).

[0069] Example 248: 4-[2,5-Dihydro-3-[6-[4-(2-methoxybenzoyl)piperazin-1-yl]hexyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile and Example 629: 4-[3-[5-[4-(ethyl-sulfonyl)piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-trifluoromethyl)benzonitrile reduce the AR content also at a concentration of 1 μM to a value up to half of the control. By the reduction of the AR content, which presumably is carried out by a destabilization of the AR protein, the inhibitory action of the antihormones on the cell proliferation is to be further intensified.

TABLE 1
AR Content (%) in LNCaP Cells After Treatment
with Selected Test
		AR Content
		[%]
Ex-		At 10	At 1
ample	Test Substance	μM	μM
248	4-[2,5-Dihydro-3-[6-[4-(2-	22	51
	methoxybenzoyl)piperazin-1-yl]hexyl]-4-methyl-
	2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
158	4-[3-[5-[4-(3,4-Dimethoxybenzoyl)piperazin-1-	22
	yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
117	4-[2,5-Dihydro-3-methyl-4-[4-[4-	36	57
	(methylsulfonyl)piperazin-1-yl]butyl]-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)-benzonitrile
90	4-[3-[4-[4-(2-Chlorobenzoyl)piperazin-1-	34
	yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
300	4-[3-[6-[4-[(4-Cyanophenyl)sulfonyl]piperazin-	35
	1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
365	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-	36	82
	dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(2,6-dichloropyridin-4-yl)piperazine-
	1-carboxamide
264	4-[3-[6-[4-[(4-Chlorophenoxy)acetyl]piperazin-1-	37
	yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
340	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,	41
	5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[3-(methyl-
	sulfanyl)phenyl]piperazine-1-carboxamide
207	4-[3-[5-[4-[(2,1,3-Benzothiadiazol-4-	42
	yl)sulfonyl]piperazin-1-yl]pentyl]-
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-
	yl]-2-(trifluoromethyl)benzonitrile
326	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,	45
	5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-3-yl]hexyl]-N-(3-fluorophenyl)-
	piperazine-1-carboxamide
330	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,	46
	5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-
	3-yl]hexyl]-N-(4-fluorophenyl)-
	piperazine-1-carboxamide
295	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-	48
	(phenylsulfonyl)piperazin-1-yl]hexyl]-1H-pyrrol-
	1-yl]-2-(trifluoromethyl)benzonitrile
296	4-[2,5-Dihydro-3-methyl-4-[6-[4-	48
	(methylsulfonyl)piperazin-
	1-yl]hexyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
96	4-[3-[4-[4-[4-(Dimethylamino)benzoyl]piperazin-	50
	1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
315	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-	52
	dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-phenylpiperazine-1-carboxamide
121	4-[3-[4-[4-[(4-Cyanophenyl)sulfonyl]piperazin-	53
	1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
93	4-[3-[4-[4-(Cyclobutylcarbonyl)piperazin-1-	53
	yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
297	4-[2,5-Dihydro-3-methyl-4-[6-[4-[(4-	59
	methylphenyl)sulfonyl]piperazin-1-yl]hexyl]-
	2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
351	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	61
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(2,6-dichlorophenyl)piperazine-1-
	carboxamide
350	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-	61
	dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(2,6-difluorophenyl)piperazine-
	1-carboxamide
324	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-	62
	dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[2-(trifluoro-
	methyl)phenyl]piperazine-1-carboxamide
270	4-[2,5-Dihydro-3-methyl-4-[6-[4-(3-methyl-1-	65
	oxobutyl)piperazin-1-yl]hexyl]-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
99	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[4-	66
	[4-[(thien-2-yl)carbonyl]piperazin-1-yl]butyl]-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
342	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-	67
	dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[4-(methyl-
	sulfanyl)phenyl]piperazine-1-carboxamide
268	4-[3-[6-[4-(4-Cyanobenzoyl)piperazin-1-	73
	yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
319	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	74
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(1-methylethyl)-piperazine-
	1-carboxamide
629	4-[3-[5-[4-(Ethylsulfonyl)piperazin-1-	54
	yl]pentyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
696	S-Methyl 4-[6-[3-[4-cyano-3-		60
	(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-
	2-thioxoimidazolidin-1-yl]hexyl]piperazine-
	1-carbothioate
524	4-[4,4-Dimethyl-5-oxo-3-[2-[4-[(thien-2-		61
	yl)carbonyl]-piperazin-1-yl]propyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)benzonitrile
546	4-[4,4-Dimethyl-3-[4-[4-(2-methyl-1-		68
	oxopropyl)piperazin-1-yl]butyl]-5-oxo-
	2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
653	4-[4,4-Dimethyl-3-[6-[4-(2-methyl-1-		71
	oxopropyl)piperazin-1-yl]hexyl]-5-oxo-
	2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
632	4-[3-[5-[4-[(4-Cyanophenyl)sulfonyl]piperazin-1-		75
	yl]pentyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)benzonitrile
Bicalu-	N-[4-Cyano-3-(trifluoromethyl)phenyl]-3-[(4-	100
tamide	fluorophenyl)sulfonyl]-2-hydroxy-2-methyl-
	propanamide
R1881	17β-Hydroxy-17α-methylestra-4,9,11-trien-3-one	250
(10 nM)

[0070] Model 2: Inhibition of the Proliferation of LNCaP Cells

[0071] For the proliferation assay, 6000 LNCaP cells/well are grown in a microtiter plate (96-well) in 50 μl of RPMI1640 medium with 5% CCS and cultivated as in Model 1. After 24 hours, the cells receive 50 μl of twice-concentrated test substance that is diluted in culture medium. The solvent concentration is 0.5% DMSO. After 4 days, the cells receive another 100 μl of once-concentrated test substance that is diluted in culture medium. After 7-8 days, the proliferation rate of the cells is determined by means of crystal violet assay (Gillies et al. Anal. Biochem. 1986, 159, 109-113). For determining antagonism, the substance treatment is performed in the presence of 0.1 nM of R1881 (1:1000 dilution of ethanolic solution). Control cells receive only 0.5% DMSO. For the agonism, the cells are treated only with test substance (without R1881).

[0072] Table 2 shows the inhibitory action of test substances on the proliferation of human androgen-dependent prostate cell line LNCaP. The inhibition of the cell proliferation is an important requirement for the therapeutic use of substances in the treatment of prostate cancer. Seven AR-destabilizing test substances that are selected according to the invention inhibit the cell proliferation in the presence of 0.1 nM of synthetic androgen R1881 with a similar to considerably lower IC50, such as the approved nonsteroidal antiandrogen bicalutamide. In a substance concentration of 1 μM, the proliferation is reduced by at least 80% compared to the cell growth in the presence of 0.1 nM of R1881. Example 696: S-Methyl 4-[6-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]piperazine-1-carbothioate and Example 653: 4-[4,4-dimethyl-3-[6-[4-(2-methyl-1-oxopropyl)piperazin-1-yl]hexyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile completely block the growth at this concentration, while bicalutamide, under these conditions, achieves only an inhibition of 85%. Up to a tested concentration of 10 μM, a proliferation-stimulating action was not observed in any one of the seven test substances.

TABLE 2
Inhibition of the Proliferation of LNCaP Cells by Test Substances.
			%
			Inhibition
Ex-		IC50	at
ample	Test Substance	[10−7 M]	1 μM
248	4-[2,5-Dihydro-3-[6-[4-(2-methoxy-	2.5	97.6
	benzoyl)-piperazin-1-yl]hexyl]-4-
	methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
315	4-[6-[1-[4-Cyano-3-(trifluoro-	3.8	80.8
	methyl)phenyl]-2,5-dihydro-4-methyl-2,
	5-dioxo-1H-pyrrol-3-yl]hexyl]-
	N-phenylpiperazine-1-carboxamide
516	4-[3-[3-[4-(2-Methoxy-	0.26	107
	benzoyl)piperazin-1-yl]propyl]-
	4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
546	4-[4,4-Dimethyl-3-[4-[4-(2-methyl-1-	0.8	97.5
	oxopropyl)-piperazin-1-yl]butyl]-5-
	oxo-2-thioxoimidazolidin-1-
	yl]-2-(trifluoromethyl)benzonitrile
602	4-[3-[5-[4-(2,2-Dimethyl-1-oxopropyl)-	0.18	92
	piperazin-1-yl]pentyl]-4,4-dimethyl-
	5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)-benzonitrile
629	4-[3-[5-[4-(Ethylsulfonyl)piperazin-1-	1.4	94.6
	yl]pentyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
638	4-[5-[3-[4-Cyano-3-(trifluoro-	0.33	95
	methyl)phenyl]-5,5-dimethyl-4-oxo-
	2-thioxoimidazolidin-1-yl]pentyl]-
	N-ethylpiperazine-1-carbothioamide
645	4-[4,4-Dimethyl-3-[6-[4-methyl-	0.26	92
	piperazin-1-yl)hexyl]-5-oxo-
	2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
648	4-[6-[3-[4-Cyano-3-(trifluoro-	0.11	99
	methyl)phenyl]-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-
	yl]hexyl]piperazine-1-carbonitrile
653	4-[4,4-Dimethyl-3-[6-[4-(2-methyl-1-	0.9	108
	oxopropyl)piperazin-1-yl]hexyl]-5-
	oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)-benzonitrile
656	4-[3-[6-[4-(2-Hydroxy-2-methyl-1-	0.26	99
	oxopropyl)-piperazin-1-yl]hexyl]-
	4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)-benzonitrile

[0073]

TABLE 3
(Continuation) Inhibition of the Proliferation
of LNCaP Cells by Test Substances.
			%
			Inhibition
Ex-		IC50	at
ample	Test Substance	[10−7 M]	1 μM
670	4-[4,4-Dimethyl-5-oxo-2-thioxo-3-	0.24	96
	[6-[4-(trifluoracetyl)piperazin-1-
	yl]hexyl]-imidazolidin-1-yl]-2-
	(trifluoromethyl)-benzonitrile
672	4-[4,4-Dimethyl-5-oxo-3-[6-[4-	0.26	100
	[(thien-2-yl)acetyl]piperazin-1-
	yl]hexyl]-2-thioxoimidazolidin-1-
	yl]-2-(trifluoromethyl)-benzonitrile
679	rel-4-[3-[6-[(2R,5S)-2,5-Dimethyl-4-	0.55	97
	[(thien-2-yl)carbonyl]piperazin-1-
	yl]hexyl]-4,4-dimethyl-5-oxo-
	2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
696	S-Methyl 4-[6-[3-[4-cyano-3-	0.2	110
	(trifluoromethyl)-phenyl]-5,5-dimethyl-
	4-oxo-2-thioxoimidazolidin-1-
	yl]hexyl]-piperazine-1-carbothioate
706	4-[3-[7-[4-(Methoxyacetyl)piperazin-1-	0.19	101
	yl]heptyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
723	4-[4,4-Dimethyl-3-[8-[4-(methyl-	0.26	90
	sulfonyl)-piperazin-1-yl]octyl]-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)-benzonitrile
Bicalu-	N-[4-Cyano-3-(trifluoro-	3.8	84.6
tamide	methyl)phenyl]-3-[(4-fluoro-
	phenyl)sulfonyl]-2-hydroxy-2-
	methylpropanamide

[0074] Model 3: Inhibition of the Proliferation of Other Cell Lines that Do Not Originate from the Prostate

[0075] To examine the growth-inhibiting action of test substances in cells that are not of prostatic origin, MaTu cells, MaTu/Adr cells, HaCaT cells and A431 cells were treated with test substances, whereby

MaTu:     means human breast cancer cell line
MaTu/Adr: means adriamycin-resistant MaTu cell line
HaCaT:    means human fibroblast cell line
A-431:    means human epidermis cell line.

[0076] Depending on the cell line, 1000-4000 cells/well were grown in RPMI 1640 medium (A431; MaTu and MaTu/Adr) or DMEM/HAM′SF12 medium (HaCaT) without phenol red with 2 mmol of L-glutamine and 10% CCS, and after a 24-hour incubation, they were treated with various concentrations of test substances diluted in culture medium. After a 3-day treatment period, the number of cells was determined by crystal violet assay, as in Model 2. The solvent control contained 0.1% ethanol.

[0077] Table 3 shows the effect of selective test substances on the proliferation of human cells that do not originate from the prostate. The substances were tested at a concentration of 10 μM, and the data correspond to the proportion, in percent, of the cell growth of the solvent control. It turns out that the test substances exerted no inhibitory action on the four different cell lines or, in individual cases, only a slight inhibitory action. Under the given test conditions, the comparison substance bicalutamide showed a slight inhibition in all cell lines except for MaTu. These results indicate that the antiproliferative action of the test substances is androgen receptor-dependent and that even at high substance concentrations in the micromolecular range, no secondary cytotoxic actions occur.

TABLE 4
Action of Selective Test Substances on the Proliferation
of Non-Prostate Cells at a Concentration of 10 μM.
	Proliferation in the Cell Line
Test Substance		MaTu/
(Example No.)	MaTu	Adr	A431	HaCaT
4-[2,5-Dihydro-3-methyl-4-[4-[4-	103 ±	94 ±	100 ±	104 ±
(methylsulfonyl)piperazin-1-	10%	4%	5%	6%
yl]butyl]-2,5-dioxo-1H-pyrrol-1-
yl]-2-(trifluoromethyl)-
benzonitrile (117)
4-[3-[4-[4-(2-Chlorobenzoyl)-	96+/	80+/	98+/	102+/
piperazin-1-yl]butyl]-2,5-dihydro-	−3%	−2%	−7%	−12%
4-methyl-2,5-dioxo-1H-pyrrol-1-
yl]-2-(trifluoromethyl)-
benzonitrile (90)
4-[2,5-Dihydro-3-[6-[4-(2-	98+/	88+/	102+/	104+/
methoxybenzoyl)piperazin-1-	−4%	−4%	−5%	−7%
yl]hexyl]-4-methyl-2,5-dioxo-1H-
pyrrol-1-yl]-2-(trifluoromethyl)-
benzonitrile (248)
4-[6-[1-[4-Cyano-3-(trifluoro-	95+/	90+/	95+/	102+/
methyl)phenyl]-2,5-dihydro-4-	−7%	−10%	−5%	−6%
methyl-2,5-dioxo-1H-pyrrol-3-
yl]hexyl]-N-phenylpiperazine-1-
carboxamide (315)
Bicalutamide	97 ±	84 ±	89 ±	92 ±
	3%	6%	7%	3%

[0078] Model 4: Antiandrogenic Action of Selective Test Substances on the Growth of Accessory Sexual Glands of Mice

[0079] The function and the size of accessory sexual glands (prostate and seminal vesicles) depend on androgens. In castrated animals, a growth of these organs is induced by androgen administration. The simultaneous treatment with antiandrogens inhibits this growth, depending on the dose.

[0080] To examine the test substances, the mice were castrated. The treatment with testosterone propionate (0.03 mg/mouse) and the test substances (formulated 2× daily 30 mg/kg s.c. in benzyl benzoate-castor oil (10:90)) was on the same day. The treatment was carried out over 7 days and at the end of the test, the weights of the seminal vesicles and prostates were determined. The inhibition, in percent, of the seminal vesicle growth was calculated relative to the control groups (with and without testosterone). As a reference substance, cyproterone acetate (30 mg/kg s.c.) was used.

[0081] The results are shown in Table 4.

[0082] The treatment with the test substances of Example 629: 4-[3-[5-[4-(ethylsulfonyl)-piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-benzonitrile and Example 546: 4-[4,4-dimethyl-3-[4-[4-(2-methyl-1-oxopropyl)piperazin-1-yl]butyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-1-yl]-2-(trifluoromethyl)-benzonitrile resulted in an almost 100% inhibition of the growth of the seminal vesicles, while the treatment with the reference substance cyproterone acetate resulted in an inhibition of only 85%. The inhibiting values for bicalutamide, determined in preceding tests, was also only at 86%.

TABLE 4
Action of Selective Test Substances on Testosterone-Stimulated
Growth of the Seminal Vesicles at a Dose of 2 × 30 mg/kg.
		%
		Inhibition
		of
		the MSB
Example	Test Substance	Growth
629	4-[3-[5-[4-(Ethylsulfonyl)piperazin-1-yl]pentyl]-4,	98
	4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
546	4-[4,4-Dimethyl-3-[4-[4-(2-methyl-1-oxopropyl)-	98
	piperazin-1-yl]butyl]-5-oxo-2-thioxoimidazolidin-
	1-yl]-2-(trifluoromethyl)benzonitrile
696	S-Methyl 4-[6-[3-[4-cyano-3-	87
	(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]hexyl]-piperazine-1-
	carbothioate
CPA	17-(Acetyloxy)-6-chloro-1β,2β-dihydro-3′H-	85
	cyclopropa[1,2]pregna-1,4,6-triene-3,20-dione
Bicaluta-	N-[4-Cyano-3-(trifluoromethyl)phenyl]-3-[(4-	86
mide	fluorophenyl)-sulfonyl]-2-hydroxy-2-
	methylpropanamide

[0083] Model 5: Antiandrogenic Action of a Selective Test Substance on the Growth of Human Prostate Cancer Xenografts in Vivo

[0084] In this invention, the action of Example 117 according to the invention: 4-[2,5-dihydro-3-methyl-4-[4-[4-(methylsulfonyl)piperazin-1-yl]butyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile on the tumor growth in vivo was studied by means of mouse-xenograft modules, in which the compound according to the invention was continuously administered subcutaneously.

[0085] The CWR22 tumor model [M. A. Wainstein, F. He, D. Robinson, H. J. Kung, S. Schwartz, J. M. Giaconia, N. L. Edgehouse, T. P. Pretlow, D. R. Bodner, E. D. Kursh, Cancer Res. 1994, 1; 54(23), 6049-52] is a hormone-dependent human prostate carcinoma model. The tumor model was established and further propagated by “serial passaging” of prostate cancer tissue, which was removed during an OP in immunodeficient hairless mice. The androgen-dependent LNCaP prostate cancer model was also established from a patient tumor. This tumor model grows both in cell culture and as a xenotransplant on immunodeficient mice (Culig, Hoffman Brit. J. Cancer, 1999, 242-251). For therapy tests, 6-week-old male hairless mice (NMRI mice, M&B, Bornholdtgard, Denmark) were supplemented with testosterone pellets (12.5 mg, 90-day release; IRA, Sarasota, Fla.). Either LNCaP cells (1.5×106 cells) or small CWR22 tumor fragments (2×2 mm) were implanted subcutaneously in the left flank of the animals. After the tumors reached a size of 20-25 mm2, the treatment with the invention substance was begun. [M. A. Wainstein, F. He, D. Robinson, H. J. Kung, S. Schwartz, J. M. Giaconia, N. L. Edgehouse, T. P. Pretlow, D. R. Bodner, E. D. Kursch, Cancer Res. 1994, 1; 54(23), 6049-52].

[0086] The results are shown in Diagrams 1 and 2.

[0087] [Key:]

[0088] Tumorfläche=Tumor surface area

[0089] Kontrolle Vehikel=Control vehicle

[0090] Kontrolle Kastration=Control castration

[0091] Bicalutamid=Bicalutamide

[0092] Substanz B=Substance B

[0093] Tage [nach Tumortransplantation]=Days [after tumor transplantation]

[0094] While the tumor grows quickly in the untreated control animals, the treatment with the invention substance results in a considerable growth inhibition of the prostate tumors. Both in the CWR22 tumor and in the LNCaP tumor, this growth inhibition is comparable to the effects of castration.

[0095] [Key:]

[0096] Tumorfläche=Tumor surface area

[0097] Kontrolle Vehikel=Control vehicle

[0098] Kontrolle Kastration=Control castration

[0099] Bicalutamid=Bicalutamide

[0100] Substanz B=Substance B

[0101] Tage [nach Tumortransplantation]=Days [After tumor transplantation]

[0102] In both models, the inhibition of the tumor growth in the treatment with the antiandrogen bicalutamide is superior. The results of the tests in the prostate cancer models show an inhibition of the tumor growth by the compound according to the invention.

[0103] In this invention, the action of a compound according to the invention on the tumor growth in vivo by means of a mouse-xenograft model was studied, in which the compound according to the invention was administered subcutaneously 2× daily over the entire treatment period. In comparison to the untreated control animals, an inhibition of tumor growth resulted. Retardation of the tumor growth was shown to be significant in castrated mice. The treatment was well-tolerated.

[0104] This invention shows that the compound according to the invention causes an inhibition of the prostate tumor growth that is superior to that of bicalutamide.

[0105] Dosage

[0106] In general, satisfactory results can be expected when the daily doses encompass a range of 5 μg to 50 mg of the compound according to the invention per kg of body weight. In larger mammals, for example humans, a recommended daily dose lies in the range of 10 μg to 30 mg per kg of body weight. Suitable dosages for the compounds according to the invention are from 0.005 to 50 mg per day per kg of body weight, depending on the age and constitution of the patient, whereby the necessary daily dose can be administered one or more times.

[0107] The formulation of the pharmaceutical preparations based on the new compounds is carried out in a way that is known in the art by the active ingredient being processed with the vehicles, fillers, substances that influence decomposition, binding agents, moisturizers, lubricants, absorbing agents, diluents, flavoring correctives, dyes, etc., that are commonly used in galenicals, and being converted into the desired form of administration. In this case, reference is made to Remington's Pharmaceutical Science, 15th Edition. Mack Publishing Company, East Pennsylvania (1980).

[0108] For oral administration, especially tablets, coated tablets, capsules, pills, powders, granulates, lozenges, suspensions, emulsions or solutions are suitable. For parenteral administration, injection and infusion preparations are possible. For intra-articular injection, correspondingly prepared crystal suspensions can be used. For intramuscular injection, aqueous and oily injection solutions or suspensions and corresponding depot preparations are used. For rectal administration, the new compounds can be used in the form of suppositories, capsules, solutions (e.g., in the form of enemas) and ointments both for systemic and for local therapy. For topical application, formulations in gels, ointments, fatty ointments, creams, pastes, powders, milks and tinctures are possible. The dosage of the compounds of general formula I should be 0.01% -20% in these preparations to achieve an adequate pharmacological action. The topical application can also be carried out by means of a transdermal system, for example a patch.

[0109] The invention also comprises the compounds of general formula I according to the invention as therapeutic active ingredients. In addition, the compounds of general formula I according to the invention are part of the invention as therapeutic active ingredients together with pharmaceutically compatible and acceptable adjuvants and vehicles. The invention also comprises a pharmaceutical composition that contains one of the pharmaceutically active compounds according to the invention or mixture thereof and a pharmaceutically compatible salt or pharmaceutically compatible adjuvants and vehicles.

[0110] Subjects of this invention are therefore also pharmaceutical compositions that contain at least one compound of general formula I, optionally together with pharmaceutically compatible adjuvants and/or vehicles.

[0111] These pharmaceutical compositions and pharmaceutical agents can be provided for oral, rectal, subcutaneous, transdermal, percutaneous, intravenous or intramuscular administration. In addition to commonly used vehicles and/or diluents, they contain at least one compound of general formula I.

[0112] The pharmaceutical agents of the invention are produced in a known way with commonly used solid or liquid vehicles or diluents and the commonly used pharmaceutical-technical adjuvants according to the desired type of administration with a suitable dosage. The preferred preparations consist of a form for dispensing that is suitable for oral administration. Such forms for dispensing are, for example, tablets, film tablets, coated tablets, capsules, pills, powders, solutions or suspensions or else depot forms.

[0113] The pharmaceutical compositions, which contain at least one of the compounds according to the invention, are preferably administered orally.

[0114] Parenteral preparations, such as injection solutions, are also considered.

[0115] In addition, for example, suppositories are also named as preparations.

[0116] Corresponding tablets can be obtained, for example, by mixing active ingredient with known adjuvants, for example inert diluents such as dextrose, sugar, sorbitol, mannitol, polyvinyl pyrrolidone, explosives such as corn starch or alginic acid, binding agents such as starches or gelatins, lubricants such as magnesium stearate or talc and/or agents for achieving a depot effect, such as carboxylpolymethylene, carboxymethyl cellulose, cellulose acetate phthalate, or polyvinyl acetate. The tablets can also consist of several layers.

[0117] Coated tablets can accordingly be produced by coating cores, which are produced analogously to the tablets, with agents that are commonly used in tablet coatings, for example polyvinyl pyrrolidone or shellac, gum arabic, talc, titanium oxide or sugar. In this case, the shell of the coated tablet can also consist of several layers, whereby the adjuvants that are mentioned above in the tablets can be used.

[0118] In addition, solutions or suspensions with the compounds of general formula I according to the invention can contain taste-improving agents such as saccharin, cyclamate or sugar, as well as, e.g., flavoring substances, such as vanilla or orange extract. In addition, they can contain suspending adjuvants such as sodium carboxymethyl cellulose or preservatives such as p-hydroxybenzoates.

[0119] The capsules that contain compounds of general formula I can be produced, for example, by the compound(s) of general formula I being mixed with an inert vehicle such as lactose or sorbitol and encapsulated in gelatin capsules.

[0120] Suitable suppositories can be produced, for example, by mixing with vehicles that are provided for this purpose, such as neutral fats or polyethylene glycol or derivatives thereof.

[0121] The compounds according to the invention can be administered combined with one or more of the following active ingredients for therapy of prostate cancers:

[0122] 1) Gonadotropic-hormone (GnRH) agonists

[0123] 2) 5α-Reductase inhibitor such as finasteride

[0124] 3) Cytostatic agents

[0125] 4) VEGF-kinase inhibitors

[0126] 5) Antigestagens

[0127] 6) Antiestrogens

[0128] 7) Antisense oligonucleotides

[0129] 8) EGF antibodies

[0130] 9) Estrogens

[0131] It is also possible, when treating prostate cancer with the compounds according to the invention, to combine their use with a clinical radiology method that is known in the art. (Laverdiere, J. et al., 1997, Intl. J. of Rad. Onc. Biol. Phys., 37, 247-252; Bolla, M. et al., 1997, New Engl. J. Med., 377, 95-300.)

[0132] Moreover, the compounds of general formula I according to the invention can be used for therapy and prophylaxis of other disease conditions that are not mentioned above.

[0133] The compounds of general formula I according to the invention can be produced as described below.

[0134] This invention also relates to the intermediate products of general formula VII

V—W—(CH2)n—I   VII

[0135] as well as of general formula VIII 8

[0136] in which

[0137] V stands for a substituted, aromatic radical of general formula II, 9

[0138] in which

[0139] A stands for an acetyl group, an acetylamino group, a cyano group, a nitro group, a trifluoromethyl group, or a halogen (fluorine, chlorine),

[0140] B stands for a hydrogen atom, a halogen (fluorine, chlorine) or a trifluoromethyl group, or

[0141] A and B together stand for a cyclic group of formula III or IV that is bonded to the aromatic ring, whereby E stands for a methylene group or an oxygen atom, 10

[0142] W stands for a heterocyclic compound of formula V, 11

[0143] in which

[0144] T stands for carbon, and a double bond is present between Q and T, and Q means a group ═C(CH3)— and U means oxygen,

[0145] n can assume one of the integral values 1, 2, 3, 4, 5, 6, 7, or 8,

[0146] i and j, independently of one another, stand for the values 1 and 2, whereby i+j can assume the value 2 or 3,

[0147] R and R′, independently of one another, can be a hydrogen atom or a methyl group,

[0148] as well as the intermediate products of general formula VII and of general formula VIII, in which

[0149] A and B together stand for a cyclic group of formula III or IV that is bonded to the aromatic ring, whereby E stands for a methylene group or an oxygen atom, 12

[0150] W stands for a heterocyclic compound of formula V, 13

[0151] in which

[0152] T stands for nitrogen, and a single bond is present between Q and T, and Q means a group —C(CH3)2— and U means sulfur,

[0153] n can assume one of the integral values 4, 5, 6, 7, or 8,

[0154] i and j, independently of one another, stand for the values 1 and 2, whereby i+j can assume the value 2 or 3,

[0155] R and R′, independently of one another, can be a hydrogen atom or a methyl group.

[0156] This invention is explained in more detail based on the examples below without being limited thereto.

[0157] Synthesis Diagrams

[0158] According to the following diagram, maleimide derivatives of chain lengths n=4 to 8 can be produced: 14

[0159] Reagents: (a) BrMg(CH2)nCl, CuBr.Me2S, THF, then MeI, HMPT, THF; (b) LiOH, H2O, THF, then HCl, extraction; (c) Aniline derivative, EtOH, MS 4 Å; (d) NaI, ethylmethylketone; (e) THF; (f) trifluoroacetic acid, CH2Cl2; (g) NEt3, THF.

[0160] According to the following diagram, maleimide derivatives of chain lengths n=1 to 8 can be produced: 15

[0161] Reagents: (b) LiOH, H2O, THF, then HCl, extraction; (c) aniline derivative, EtOH, MS 4 Å; (e) THF; (f) Trifluoroacetic acid, CH2Cl2; (g) NEt3, THF; (h) BrMg(CH2)m—CH═CH2, CuBr.Me2S, THF, then MeI, HMPT, THF; (i) BrMg(CH2)nOPG, CuBr Me2S, THF, then MeI, HMPT, THF; (PG=protective group); (j) Protection removal; (k) 9-BBN, then NaOH, H2O2; (l) OsO4; (m) NaIO4; (n) Na(Oac)3BH; (s) Imidazole, iodine, triphenylphosphine.

[0162] According to the following diagram, thiohydantoin derivatives of chain lengths n=4 to 8 can be produced: 16

[0163] Reagents: (d) NaI, ethylmethylketone; (e) THF; (f) Trifluoroacetic acid, CH2Cl2; (g) NEt3, THF; (o) CSCl2, H2O; (p) NEt3, THF; (q) 4 M HCl; (r) RSO2Cl, NEt3, CH2Cl2.

[0164] According to the following diagram, thiohydantoin derivatives of chain lengths n=2 to 8 can be produced: 17

[0165] Reagents: (f) Trifluoroacetic acid, CH2Cl2; (g) NEt3, THF; (o) CSCl2, H2O; (p) NEt3, THF; (q) 4 M HCl.

[0166] Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following preferred specific embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.

[0167] In the foregoing and in the following examples, all temperatures are set forth uncorrected in degrees Celsius and, all parts and percentages are by weight, unless otherwise indicated.

[0168] Production Process

EXAMPLE 1

[0169] 1,1-Dimethylethyl 4-[5-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]piperazine-1-carboxylate

[0170] 1a) Dimethyl (Z)-2-(5-chloropentyl)-3-methyl-2-butenedicarboxylate

[0171] For the production of a Grignard reagent, 4.1 g of magnesium chips in 22 ml of tetrahydrofuran was introduced under nitrogen atmosphere, mixed with 31.3 g of 1-bromo-5-chloropentane in 200 ml of tetrahydrofuran, and it was stirred for 1 hour at room temperature. This mixture was then added in drops under nitrogen atmosphere and while being stirred at −35 to −40° C. to a suspension of 34.7 g of copper(I)-bromide-dimethyl sulfide complex in 700 ml of tetrahydrofuran, and it was stirred for another 2 hours at −40° C. Then, it was cooled to −65 to −70° C., and a solution of 20 g of dimethyl acetylenedicarboxylate and 48 ml of hexamethylphosphoric acid triamide in 290 ml of tetrahydrofuran were added in drops at this temperature while being stirred; after 5 minutes, a solution of 95 ml of hexamethylphosphoric acid triamide in 95 ml of tetrahydrofuran was added at −65 to −70° C., it was stirred for another 5 minutes at this temperature, 100 g of iodomethane in 280 ml of tetrahydrofuran was added in drops, and this mixture was heated overnight to room temperature. For working-up, it was cooled to −60° C. while being stirred, 410 ml of saturated ammonium chloride solution (with concentrated ammonia solution set at a pH of 8) was added in drops, heated to room temperature and stirred for 45 minutes at room temperature. This mixture was extracted four times with ethyl acetate, the combined organic phases were washed with saturated ammonium chloride solution (with concentrated ammonia solution set at a pH of 8) until the organic phase was light blue and then washed with water until the organic phase was colorless. After washing with saturated sodium chloride solution, drying on sodium sulfate and concentration by evaporation, it was chromatographed on silica gel with ethyl acetate/hexane, and thus in addition to 7.2 g of dimethyl (E)-2-(5-chloropentyl)-3-methyl-2-butenedicarboxylate, in each case 10.0 g of the title compound was obtained as a yellowish oil.

[0172] 1 H-NMR (300 MHz, CDCl3): δ [ppm]=3.76 s (3H, OCH3); 3.75 s (3H, OCH3); 3.53 t (J=6.5 Hz, 2H, CH2Cl); 2.35 tbr (J=7 Hz, 2H, CH2olefin); 1.95 s (3H, CH3); 1.78 m (2H, CH2); 1.47 m (4H, CH2).

[0173] 1b) 3-(5-Chloropentyl)-4-methyl-2,5-furandione

[0174] 86 ml of water as well as 164 ml of a solution of lithium hydroxide in water (1 mol/l) were added to a solution of 7.16 g of (Z)-dimethyl 2-(5-chloropentyl)-3-methyl-2-butenedicarboxylate that was stirred under nitrogen atmosphere, and it was stirred for 2 days at room temperature. For working-up, it was concentrated by evaporation, the residue was dissolved in 290 ml of water, set at pH 2 with hydrochloric acid (2 mol/l) while being cooled in an ice bath and extracted three times with diethyl ether. The combined organic phases were washed with saturated sodium chloride solution, dried on sodium sulfate, concentrated by evaporation, and the title compound was thus obtained as a yellowish oil.

[0175] 1 H-NMR (300 MHz, CDCl3): δ [ppm]=3.54 t (J=6.5 Hz, 2H, CH2Cl); 2.48 tbr (J=7.5 Hz, 2H, CH2olefin); 2.08 sbr (3H, CH3); 1.81 m (2H, CH2); 1.63 m (2H, CH2); 1.51 m (2H, CH2).

[0176] 1c) 4-[3-(5-Chloropentyl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0177] A mixture of 9.46 g of 3-(5-chloropentyl)-4-methyl-2,5-furandione and 8.13 g of 4-amino-2-(trifluoromethyl)benzonitrile in 22 ml of ethanol was mixed under a nitrogen atmosphere with 2.5 g of an activated molecular sieve (0.3 nm), and it was stirred for 2 days at 90° C. For working-up, the molecular sieve was filtered off after cooling, washed with ethanol, and the combined ethanol solutions were concentrated by evaporation. The residue was taken up in ethyl acetate and washed with water as well as saturated sodium chloride solution. After drying on sodium sulfate and concentration by evaporation, it was chromatographed on silica gel with ethyl acetate/hexane/toluene, and 11.69 g of the title compound was thus obtained as a white solid.

[0178] 1 H-NMR (300 MHz, CDCl3): δ [ppm]=8.06 sbr (1H, aryl); 7.91 s (2H, aryl); 3.56 t (J=7 Hz, 2H, CH2Cl); 2.53 t (J=7.5 Hz, 2H, CH2olefin); 2.11 s (3H, CH3); 1.83 m (2H, CH2); 1.69−1.50 m (4H, CH2).

[0179] 1d) 4-[2,5-Dihydro-3-(5-iodopentyl)-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0180] A mixture of 11.68 g of 4-[3-(5-chloropentyl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile and 18.2 g of sodium iodide in 180 ml of ethylmethylketone was stirred under a nitrogen atmosphere for 19 hours at 80° C. After cooling, it was diluted with ethyl acetate and washed with water as well as saturated sodium chloride solution. After drying on sodium sulfate and concentration by evaporation, 11.26 g of the title compound was obtained as a white solid.

[0181] 1 H-NMR (300 MHz, CDCl3): δ [ppm]=8.06 sbr (1H, aryl); 7.91 s (2H, aryl); 3.20 t (J=7 Hz, 2H, CH2I); 2.52 t (J=7.5 Hz, 2H, CH2olefin); 2.11 s (3H, CH3); 1.86 m (2H, CH2); 1.63 m (2H, CH2); 1.50 m (2H, CH2).

[0182] 1e) 1,1-Dimethylethyl 4-[5-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]piperazine-1-carboxylate

[0183] 1.56 g of 1,1-dimethylethyl piperazine-1-carboxylate was added under a nitrogen atmosphere to a solution of 2.0 g of 4-[2,5-dihydro-3-(5-iodopentyl)-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile in 53 ml of tetrahydrofuran, and this mixture was stirred for 7 days at room temperature. For working-up, it was diluted with ethyl acetate and washed with semi-saturated sodium bicarbonate solution. After drying on sodium sulfate and concentration by evaporation, it was chromatographed with methanol/dichloromethane on silica gel, and thus 2.2 g of the title compound was obtained as a yellowish oil.

[0184] 1 H-NMR (300 MHz, CDCl3): δ [ppm]=8.06 sbr (1H, aryl); 7.90 m (2H, aryl); 3.43 m (4H, piperazine); 2.50 tbr (J=7.5 Hz, 2H, CH2olefin); 2.40−2.31 m (4H, piperazine); 2.40−2.31 m (2H, CH2piperazine); 2.09 s (3H, CH3); 1.66−1.36 m (6H, CH2); 1.45 s (9H, CH3).

EXAMPLE 2

[0185] 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-(piperazin-1-yl)pentyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0186] 60 ml of trifluoroacetic acid was added in drops to a solution of 4.5 g of 1,1-dimethylethyl 4-[5-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]piperazine-1-carboxylate in 120 ml of dichloromethane under a nitrogen atmosphere and while being cooled in an ice bath, and it was stirred for 1 hour at room temperature. For working-up, the reaction solution was diluted with 250 ml of toluene, and the mixture was concentrated by evaporation. The residue was taken up in ethyl acetate and washed with saturated sodium bicarbonate solution. After drying on sodium sulfate and concentration by evaporation, it was chromatographed with methanol/dichloromethane on silica gel, and 3.5 g of the title compound was thus obtained as a white solid.

[0187] 1 H-NMR (300 MHz, CD3OD): δ [ppm]=8.13 dbr (J=2 Hz, 1H, aryl); 8.08 dbr (J=8.5 Hz, 1H, aryl); 8.01 dd (J=8.5 Hz+2 Hz, 1H, aryl): 3.18 m (4H, piperazine); 2.69 m (4H, piperazine); 2.53 tbr (J=7.5 Hz, 2H, CH2olefin); 2.47 tbr (J=7.5 Hz, 2H, CH2piperazine); 2.07 s (3H, CH3); 1.69−1.53 m (4H, CH2); 1.44 m (2H, CH2).

EXAMPLE 3

[0188] 4-[2,5-Dihydro-3-methyl-4-[5-[4-[2-(methylsulfanyl)phenyl]piperazin-1-yl]pentyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0189] 9 mg of 1-(2-thiomethylphenyl)piperazine in 0.5 ml of tetrahydrofuran was added to a solution of 10 mg of 4-[2,5-dihydro-3-(5-iodopentyl)-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile in 0.4 ml of tetrahydrofuran, and the mixture was stirred for 2 days at room temperature. For working-up, the reaction mixture was diluted with ethyl acetate and washed with semi-saturated sodium bicarbonate solution. After the organic phase was concentrated by evaporation, it was chromatographed with methanol/dichloromethane on silica gel, and 6 mg of the title compound was thus obtained as a yellowish oil.

[0190] ESI-MS: 557.

EXAMPLE 4

[0191] 4-[3-[5-[4-(4-Cyanobenzoyl)piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0192] 0.2 ml of a solution of triethylamine in tetrahydrofuran (1.5 mol/l) and 7 mg of 4-cyanobenzoyl chloride in 0.4 ml of tetrahydrofuran were added to a solution of 9 mg of 4-[2,5-dihydro-3-methyl-2,5-dioxo-4-[5-(piperazin-1-yl)-pentyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile in 0.4 ml of tetrahydrofuran, and the mixture was stirred for 8 hours at room temperature. For working-up, the reaction mixture was diluted with ethyl acetate and washed with semi-saturated sodium bicarbonate solution. After the organic phase was concentrated by evaporation, it was chromatographed with methanol/dichloromethane on silica gel, and 7 mg of the title compound was thus obtained as a yellowish oil.

[0193] ESI-MS: 564.

EXAMPLE 5

[0194] 4-[3-[5-[4-[(3-Fluorophenyl)sulfonyl]piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0195] 0.2 ml of a solution of triethylamine in tetrahydrofuran (1.5 mol/l) and 8 mg of 3-fluorophenylsulfonyl chloride in 0.4 ml of tetrahydrofuran were added to a solution of 9 mg of 4-[2,5-dihydro-3-methyl-2,5-dioxo-4-[5-(piperazin-1-yl)pentyl]-1H-pyrrol-1yl]-2-(trifluoromethyl)benzonitrile in 0.4 ml of tetrahydrofuran, and the mixture was stirred for 8 hours at room temperature. For working-up, the reaction mixture was diluted with ethyl acetate and washed with semi-saturated sodium bicarbonate solution. After the organic phase was concentrated by evaporation, it was chromatographed with methanol/dichloromethane on silica gel, and 6 mg of the title compound was thus obtained as a white solid.

[0196] ESI-MS: 593.

Example 6

[0197] 4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]-N-[4-(dimethylamino)phenyl]piperazine-1-carboxamide

[0198] 0.2 ml of a solution of triethylamine in tetrahydrofuran (1.5 mol/l) and 7 mg of 4-(dimethylamino)phenylisocyanate in 0.4 ml of tetrahydrofuran were added to a solution of 9 mg of 4-[2,5-dihydro-3-methyl-2,5-dioxo-4-[5-(piperazin-1-yl)pentyl]-1H-pyrrol-1- yl]-2-(trifluoromethyl)benzonitrile in 0.4 ml of tetrahydrofuran, and the mixture was stirred for 8 hours at room temperature. For working-up, the reaction mixture was diluted with ethyl acetate and washed with semi-saturated sodium bicarbonate solution. After the organic phase was concentrated by evaporation, it was chromatographed with methanol/dichloromethane on silica gel, and 3 mg of the title compound was thus obtained as a yellowish oil.

[0199] ESI-MS: 597.

EXAMPLE 7

[0200] 4-[2,5-Dihydro-3-methyl-4-[3-[4-(1-methylethylsulfonyl)piperazin-1-yl]propyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0201] 7a) Dimethyl (Z)-2-methyl-3-(prop-2-enyl)-2-butenedicarboxylate

[0202] A solution of allylmagnesium chloride in tetrahydrofuran (8.5 ml, c=2.0 M) was added in drops under nitrogen atmosphere and while being stirred at −35 to −40° C. to a suspension of 3.47 g of copper(I)-bromide-dimethylsulfide complex in 70 ml of tetrahydrofuran, and it was stirred for 2 hours at −40° C. Then, it was cooled to −70° C., and a solution of 2.0 g of dimethyl acetylenedicarboxylate and 4.8 ml of hexamethylphosphoric acid triamide in 29 ml of tetrahydrofuran was added in drops at this temperature while being stirred. After 5 minutes, a solution of 9.5 ml of hexamethylphosphoric acid triamide in 9.5 ml of tetrahydrofuran was added at −70° C. It was stirred for 5 minutes at this temperature, then 4.2 ml of iodomethane in 28 ml of tetrahydrofuran was added in drops, and this mixture was heated overnight to room temperature. For working-up, it was cooled to −60° C. while being stirred, 200 ml of saturated ammonium chloride solution (with concentrated ammonia solution set at pH 8) was added in drops, it was heated to room temperature and stirred for 45 minutes at room temperature. This mixture was extracted four times with ethyl acetate, the combined organic phases were washed with saturated ammonium chloride solution (with concentrated ammonia solution set at pH 8) until the organic phase was light blue and was then washed with water until the organic phase was colorless. After washing with saturated sodium chloride solution, drying on sodium sulfate and concentration by evaporation, it was chromatographed on silica gel with ethyl acetate/hexane, and 980 mg of the title compound in addition to 950 mg of dimethyl (E)-2-methyl-3-(prop-2-enyl)-2-butenedicarboxylate in each case were obtained as a yellowish oil.

[0203] 1 H-NMR (300 MHz, CDCl3): δ [ppm]=5.8 m (1H); 5.1 m (2H); 3.77 s (3H); 3.75 s (3H); 3.10 d (J=6.58 Hz, 2H); 1.96 s (3H).

[0204] ESI-MS: 198

[0205] 7b) 3-Methyl-4-(prop-2-enyl)-2,5-furandione

[0206] 10 ml of water as well as 16 ml of a solution of lithium hydroxide in water (1 mol/l) were added to a solution, stirred under a nitrogen atmosphere, of 980 mg of the compound, produced under 7a, in 10 ml of tetrahydrofuran, and it was stirred for 2 days at room temperature. For working-up, it was concentrated by evaporation, the residue was dissolved in 30 ml of water, the pH was set at 2 with hydrochloric acid (2 mol/l) while being cooled in an ice bath, and it was extracted three times with diethyl ether. The combined organic phases were washed with saturated sodium chloride solution, dried on sodium sulfate, concentrated by evaporation, and 750 mg of the title compound was thus obtained as a yellowish oil.

[0207] ESI-MS: 152

[0208] 7c) 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-(prop-2-enyl)-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0209] A mixture of 750 mg of the compound, produced under 7b, and 920 mg of 4-amino-2-(trifluoromethyl)benzonitrile in 10 ml of ethanol was mixed under a nitrogen atmosphere with 0.5 g of an activated molecular sieve (0.3 nm) and stirred for 2 days at 90° C. For working-up, the molecular sieve was filtered off after cooling, washed with ethanol, and the combined ethanol solutions were concentrated by evaporation. The residue was taken up in ethyl acetate and washed with water as well as saturated sodium chloride solution. After drying on sodium sulfate and concentration by evaporation, it was chromatographed on silica gel with ethyl acetate/hexane, and 731 mg of the title compound was thus obtained as a colorless oil.

[0210] ESI-MS: 320

[0211] 7d) 4-[2,5-Dihydro-3-(3-hydroxypropyl)-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0212] A solution of 720 mg of the compound, produced under 7c, in 15 ml of THF was mixed under a nitrogen atmosphere at −78° C. with 5.9 ml of a 0.5 molar solution of 9-borabicyclo (3.3.1)nonane. The solution was slowly heated to room temperature and stirred overnight at room temperature. The solution that was stirred vigorously was mixed at 0° C. with 3.1 ml of 10% sodium hydroxide solution and with 2.7 ml of 33% hydrogen peroxide solution, and it was stirred for 12 hours at room temperature. For working-up, it was mixed with water (20 ml) and extracted three times with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried on sodium sulfate, concentrated by evaporation, chromatographed on silica gel with ethyl acetate/hexane, and 623 mg of the title compound was thus obtained as a yellowish oil.

[0213] ESI-MS: 338

[0214] 7e) 4-[2,5-Dihydro-3-(3-iodopropyl)-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0215] A solution of 610 mg of the compound, produced under 7d, of 565 mg of triphenylphosphine and 183 mg of 1H-imidazole in 50 ml of THF was mixed under a nitrogen atmosphere with 545 mg of iodine. The solution was stirred overnight at room temperature and then mixed with 20 ml of water and 10 ml of 20% sodium thiosulfate solution and extracted three times with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried on sodium sulfate, concentrated by evaporation, chromatographed on silica gel with ethyl acetate/hexane, and 572 mg of the title compound was thus obtained as a yellowish oil.

[0216] ESI-MS: 448

[0217] 7f) 1,1-Dimethylethyl 4-[3-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]propyl]piperazine-1-carboxylate

[0218] The production of the title compound was carried-out analogously to the reaction described under 1e. Starting from 550 mg of the compound that was produced under 7e, 372 mg of the title compound was obtained.

[0219] ESI-MS: 506

[0220] 7g) 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[3-(piperazin-1-yl)propyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0221] 350 mg of the compound that was produced under 7f was stirred with 3 ml of trifluoroacetic acid in 10 ml of dichloromethane for 6 hours at room temperature. The reaction mixture was concentrated by evaporation in a vacuum and concentrated by evaporation several times with toluene in a vacuum, taken up in methanol, set at a pH of 8 to 9 with anion exchanger (Bio-Rad AG 1-X8, OH form), filtered, and concentrated by evaporation in a vacuum. 227 mg of the title compound was obtained as a crude product, which was further reacted in this form.

[0222] ESI-MS: 406

[0223] 7h) 4-[2,5-Dihydro-3-methyl-4-[3-[4-(1-methylethylsulfonyl)piperazin-1-yl]propyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0224] 25 mg of the compound that was produced under 7g was stirred with 11 μl of 1-methylethylsulfonyl chloride and 25 μl of triethylamine in 2 ml of tetrahydrofuran for 16 hours at room temperature. The reaction mixture was concentrated by evaporation in a vacuum. Column chromatography on silica gel with a mixture that consists of hexane/ethyl acetate yielded 23 mg of the title compound as a colorless oil.

[0225] ESI-MS: 512

EXAMPLE 8

[0226] 4-[2,5-Dihydro-3-methyl-4-[[4-(1-methylethylsulfonyl)piperazin-1-yl]methyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0227] 8a) Dimethyl (Z)-2-ethenyl-3-methyl-2-butenedicarboxylate

[0228] The reaction of vinylmagnesium chloride with 5 g of dimethyl acetylenedicarboxylate analogously to the instructions described under 7a yielded 1.8 g of the title compound as a yellowish oil.

[0229] ESI-MS: 184

[0230] 8b) 4-[3-Ethenyl-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0231] The reaction of 1.8 g of the compound, produced under 8a, analogously to the instructions described under 7b and 7c yielded 1.1 g of the title compound as a colorless oil.

[0232] ESI-MS: 306

[0233] 8c) 4-[3-(1,2-Dihydroxyethyl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0234] A solution of 1.1 g of the compound, produced under 8b, in 50 ml of acetone was mixed at room temperature with a solution of 640 mg of N-methylmorpholine-N-oxide in 10 ml of water and 0.9 ml of a 10% solution of osmium tetraoxide. It was stirred for 30 hours at room temperature, then mixed with saturated sodium thiosulfate solution and extracted three times with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried on sodium sulfate, concentrated by evaporation, chromatographed with dichloromethane/methanol on silica gel, and 770 mg of the title compound was thus obtained as a colorless oil.

[0235] ESI-MS: 340

[0236] 8d) 4-[3-Formyl-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0237] A solution of 750 mg of the compound, produced under 8c, in 50 ml of dichloromethane was mixed at room temperature in succession with 619 mg of sodium periodate and with 5 ml of a 10% aqueous solution of sodium bicarbonate. It was stirred for 5 hours at room temperature, then mixed with sodium sulfate and diluted with 50 ml of dichloromethane. The mixture was filtered and concentrated by evaporation. 705 mg of the title compound was obtained as a crude product, which was further reacted in this form.

[0238] ESI-MS: 308

[0239] 8e) 4-[2,5-Dihydro-3-methyl-4-[[4-(1-methylethylsulfonyl)piperazin-1-yl]methyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0240] 25 mg of the compound, produced under 8d, in 1 ml of 1,2-dichloroethane was mixed with 19 mg of 1-(1-methylethylsulfonyl)piperazine and stirred for 15 minutes at room temperature. 25 mg of sodium tris-acetoxy borohydride was added in portions, and it was stirred for 2 hours at room temperature. The reaction mixture was mixed with 10 ml of sodium bicarbonate solution, stirred for 15 minutes at room temperature, and extracted three times with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried on sodium sulfate, concentrated by evaporation and chromatographed with dichloromethane/methanol on silica gel. 17 mg of the title compound was obtained as a colorless oil.

[0241] ESI-MS: 484

EXAMPLE 9

[0242] 4-[2,5-Dihydro-3-methyl-4-[7-[4-(1-methylethylsulfonyl)piperazin-1-yl]heptyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0243] 9a) Dimethyl (Z)-2-[7-[(4-methoxyphenyl)methoxy]heptyl]-3-methyl-2-butenedicarboxylate

[0244] The reaction of 12.4 g of 1-[[(7-chloroheptyl)oxy]methyl]-4-methoxybenzene with 5.0 g of dimethyl acetylene dicarboxylate analogously to the instructions described under 1a yielded 4.18 g of the title compound as a yellowish oil.

[0245] ESI-MS: 378

[0246] 9b) 4-[2,5-Dihydro-3-[7-[(4-methoxyphenyl)methoxy]heptyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0247] The reaction of 4.10 g of the compound, produced under 9a, analogously to the instructions described under 7b and 7c yielded 3.35 g of the title compound as a colorless oil.

[0248] ESI-MS: 514

[0249] 9c) 4-[2,5-Dihydro-3-(7-hydroxyheptyl)-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0250] 3.30 g of the compound, produced under 9b, in 100 ml of dichloromethane was mixed with 10 ml of water and 1.90 g of 4,5-dichloro-3,6-dioxocyclohexa-1,4-diene-1,2-dicarbonitrile, and it was stirred for 5 hours at room temperature. The reaction mixture was mixed with 20 ml of sodium bicarbonate solution and extracted three times with dichloromethane. The combined organic phases were washed with saturated sodium chloride solution, dried on sodium sulfate, concentrated by evaporation and chromatographed with dichloromethane/methanol on silica gel. 2.05 g of the title compound was obtained as a colorless oil.

[0251] ESI-MS: 394

[0252] 9d) 4-[3-(7-Iodoheptyl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0253] The reaction of 2.0 g of the compound, produced under 9c, analogously to the instructions that are described under 7e, yielded 1.99 g of the title compound as a colorless oil.

[0254] ESI-MS: 504

[0255] 9e) 1,1-Dimethylethyl 4-[7-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]heptyl]piperazine-1-carboxylate

[0256] The production of the title compound was carried out analogously to the reaction that was described under 1e. Starting from 1.95 g of the compound that was produced under 9c, 1.01 g of the title compound was obtained.

[0257] ESI-MS: 562

[0258] 9f) 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[7-(piperazin-1-yl)heptyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0259] The production of the title compound was carried out analogously to the reaction that was described under 7g. Starting from 1.0 g of the compound that was produced under 9e, 707 mg of the title compound was obtained.

[0260] ESI-MS: 462

[0261] 9g) 4-[2,5-Dihydro-3-methyl-4-[7-[4-(1-methylethylsulfonyl)piperazin-1-yl]heptyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0262] The production of the title compound was carried out analogously to the reaction that was described under 7h. Starting from 25 mg of the compound that was produced under 9f, 20 mg of the title compound was obtained.

[0263] ESI-MS: 568

EXAMPLE 10

[0264] 1,1-Dimethylethyl 4-[5-[3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]pentyl]piperazine-1-carboxylate

[0265] 10a) 5-[3-(5-Hydroxypentyl)-5-imino-4,4-dimethyl-2-thioxoimidazolidin-1-yl]isobenzofuran-1(3h)-one

[0266] 5 g of 5-aminoisobenzofuran-1(3H)-one, whose production is described in R. N. Warrener, L. Liu, R. A. Russell, Tetrahedron 1998, 54, 7485-7496, with 2.8 ml of thiophosgene in 70 ml of water, was stirred for one hour at room temperature under nitrogen atmosphere. The reaction mixture was filtered. The residue was washed with water and then dried for 30 minutes at 60° C. in a vacuum. The thus obtained crude isothiocyanate was combined with the cyanoamine that was produced by four hours of stirring of 520 μl of acetone cyanohydrin with 617 μl of 5-aminopentan-1-ol at room temperature, and it was heated to boiling with 4.7 ml of triethylamine in 100 ml of tetrahydrofuran for 30 minutes. After concentration by evaporation in a vacuum, the title compound was obtained as a crude product, which was immediately further reacted.

[0267] 10b) 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-(5-hydroxypentyl)-5,5-dimethyl-2-thioxoimidazolidin-4-one

[0268] The crude product that was produced under 10a was stirred with 17 ml of 4 molar aqueous hydrochloric acid in 150 ml of methanol overnight at room temperature. The reaction mixture was then poured onto saturated, aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic phase was washed with saturated aqueous sodium chloride solution, dried on sodium sulfate, filtered and concentrated by evaporation in a vacuum. Column chromatography on silica gel with a mixture that consists of hexane/ethyl acetate yields 4.0 g of the title compound as a colorless foam.

[0269] 1 H-NMR (300 MHz, CDCl3): δ [ppm]=8.03 d (J=8 Hz, 1H, aryl); 7.53 ddbr (J=8 Hz+1 Hz, 1H, aryl); 7.52 d (J=1 Hz, 1H, aryl); 5.37 s (1H, CH2O); 3.71 m (2H, CH2OH); 3.69 m (2H, CH2N); 1.89 m (2H, CH2); 1.66 m (2H, CH2); 1.58 s (6H, CH3); 1.49 m (2H, CH2).

[0270] 10c) 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[5-[[(4-methylphenyl)-sulfonyl]oxy]pentyl]-2-thioxoimidazolidin-4-one

[0271] 3.9 g of the compound that was produced under 10b was stirred with 12.3 g of p-toluenesulfonic acid chloride and 15 ml of triethylamine in 100 ml of dichloromethane for one hour at room temperature. The reaction mixture was poured into saturated aqueous sodium bicarbonate solution and extracted with dichloromethane. The organic phase was washed with saturated aqueous sodium chloride solution, dried on sodium sulfate, filtered and concentrated by evaporation in a vacuum. Column chromatography on silica gel with a mixture that consists of hexane/ethyl acetate yields 5.15 g of the title compound as a colorless foam.

[0272] Flash point 164.9° C. (methanol)

[0273] 1H-NMR (300 MHz, CDCl3): δ [ppm]=8.04 d (J=8 Hz, 1H, aryl); 7.81 d (J=9 Hz, 2H, tolyl); 7.54 dbr (J=8 Hz, 1H, aryl); 7.53 sbr (1H, aryl); 7.37 d (J=9 Hz, 2H, tolyl); 5.38 s (1H, CH2O); 4.08 t (J=6 Hz, 2H, CH2OTs); 3.68 m (2H, CH2N); 1.86 m (2H, CH2); 1.76 m (2H, CH2); 1.58 s (6H, CH3); 1.49 m (2H, CH2).

[0274] 10d) 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-(5-iodopentyl)-2-thioxo-imidazolidin-4-one

[0275] 5.15 g of the compound that was produced under 10c was heated to boiling with 3 g of sodium iodide in 100 ml of acetone for one hour. The reaction mixture was filtered at room temperature and concentrated by evaporation in a vacuum. Column chromatography on silica gel with a mixture that consists of hexane/ethyl acetate yields 4.16 g of the title compound as a yellowish foam.

[0276] 1 H-NMR (300 MHz, CDCl3): δ [ppm]=8.03 d (J=8 Hz, 1H, aryl); 7.53 ddbr (J=8 Hz+2 Hz, 1H, aryl); 7.52 sbr (1H, aryl); 5.37 s (1H, CH2O); 3.70 m (2H, CH2N); 3.23 t (J=7 Hz, 2H, CH2I); 1.89 m (4H, CH2); 1.59 s (6H, CH3); 1.53 m (2H, CH2).

[0277] 10e) 1,1-Dimethylethyl-4-[5-[3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]pentyl]piperazine-1-carboxylate

[0278] 1 g of the compound that was produced under 10d was stirred with 790 mg of 1,1-dimethylethyl piperazine-1-carboxylate and 591 μl of triethylamine for three days at room temperature. The reaction mixture was concentrated by evaporation in a vacuum. Column chromatography on silica gel with a mixture that consists of hexane/ethyl acetate yields 903 mg of the title compound as a yellowish foam.

[0279] 1 H-NMR (300 MHz, CDCl3): δ [ppm]=8.04 d (J=8 Hz, 1H, aryl); 7.54 dbr (J=8 Hz, 1H, aryl); 7.52 sbr (1H, aryl); 5.37 s (1H, CH2O); 3.69 m (2H, CH2N); 3.44 m (4H, piperazine); 2.38 m (4H, piperazine); 2.36 m (2H, CH2piperazine); 1.86 m (2H, CH2); 1.58 s (6H, CH3); 1.57 m (2H, CH2); 1.46 s (9H, tBu); 1.42 m (2H, CH2).

EXAMPLE 11

[0280] 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-[5-(piperazin-1-yl)pentyl]-5,5-dimethyl-2-thioxoimidazolidin-4-one

[0281] 450 mg of the compound that was produced under 10e was stirred with 653 μl of trifluoroacetic acid in 8.5 ml of dichloromethane for 24 hours at room temperature. The reaction mixture was concentrated by evaporation in a vacuum and concentrated by evaporation in a vacuum several times with toluene, taken up in methanol, set at a pH of 8 to 9 with anion exchanger (Bio-Rad AG 1-X8, OH form), filtered, and concentrated by evaporation in a vacuum. 313 mg of the title compound was obtained as a crude product, which was further reacted in this form.

[0282] 1 H-NMR (300 MHz, CD3OD): δ [ppm]=7.96 d (J=8 Hz, 1H, aryl); 7.57 dbr (J=8 Hz, 1H, aryl); 7.65 sbr (1H, aryl); 5.43 s (1H, CH2O); 3.75 m (2H, CH2N); 2.87 m (4H, piperazine); 2.48 m (4H, piperazine); 2.39 m (2H, CH2piperazine); 1.88 m (2H, CH2); 1.61 m (2H, CH2); 1.58 s (6H, CH3); 1.42 m (2H, CH2).

EXAMPLE 12

[0283] 4-[5-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]pentyl]-N-ethylpiperazine-1-carbothioamide

[0284] 20 mg of the compound that was produced under 11 was heated to 80° C. with 7.7 ml of isothiocyanatoethane and 12.4 μl of triethylamine in 3 ml of tetrahydrofuran for 6 hours. The reaction mixture was concentrated by evaporation in a vacuum. Column chromatography on silica gel with a mixture that consists of hexane/ethyl acetate yields 11 mg of the title compound as a colorless oil.

[0285] 1 H-NMR (300 MHz, CDCl3): δ [ppm]=8.02 d (J=8 Hz, 1H, aryl); 7.53 dbr (J=8 Hz, 1H, aryl); 7.51 sbr (1H, aryl); 5.47 tbr (J=5 Hz, 1H, NH); 5.37 s (1H, CH2O); 3.81 m (4H, piperazine); 3.70 qd (J=7 Hz+5 Hz, 2H, CH2N); 3.67 m (2H, CH2N); 2.47 m (4H, piperazine); 2.38 m (2H, CH2piperazine); 1.86 m (2H, CH2); 1.57 s (6H, CH3); 1.57 m (2H, CH2); 1.41 m (2H, CH2); 1.24 t (J=7 Hz, 3H, CH3).

EXAMPLE 13

[0286] S-Methyl 4-[5-[3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]pentyl]piperazine-1-carbothioate

[0287] 15.5 mg of the compound that was produced under 11 was refluxed for 4 hours with 6.2 ml of S-methyl chlorothioformate and 10 μl of triethylamine in 1 ml of tetrahydrofuran. The reaction mixture was concentrated by evaporation in a vacuum. Column chromatography on silica gel with a mixture that consists of hexane/ethyl acetate yields 8 mg of the title compound as a colorless oil.

[0288] 1 H-NMR (300 MHz, CDCl3): δ [ppm]=8.03 d (J=8 Hz, 1H, aryl); 7.53 dbr (J=8 Hz, 1H, aryl); 7.52 sbr (1H, aryl); 5.37 s (1H, CH2O); 3.69 m (2H, CH2N); 3.56 m (4H, piperazine); 2.43 m (4H, piperazine); 2.38 m (2H, CH2piperazine); 2.33 s (3H, CH3); 1.86 m (2H, CH2); 1.57 s (6H, CH3); 1.56 m (2H, CH2); 1.42 m (2H, CH2).

EXAMPLE 14

[0289] 4-[5-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]pentyl]-N,N-diethylpiperazine-1-carboxamide

[0290] 15.5 mg of the compound that was produced under 11 was refluxed for 4 hours with 9.8 ml of diethylcarbamidoyl chloride and 10 μl of triethylamine in 1 ml of tetrahydrofuran. The reaction mixture was concentrated by evaporation in a vacuum. Column chromatography on silica gel with a mixture that consists of hexane/ethyl acetate yields 6 mg of the title compound as a colorless oil.

[0291] 1 H-NMR (300 MHz, CDCl3): δ [ppm]=8.03 d (J=8 Hz, 1H, aryl); 7.53 dbr (J=8 Hz, 1H, aryl); 7.52 sbr (1H, aryl); 5.37 s (1H, CH2O); 3.69 m (2H, CH2N); 3.23 m (4H, piperazine); 3.19 q (J=7 Hz, 4H, CH2N); 2.43 m (4H, piperazine); 2.37 m (2H, CH2piperazine); 1.86 m (2H, CH2); 1.59 m (2H, CH2); 1.58 s (6H, CH3); 1.41 m (2H, CH2); 1.11 t (J=7 Hz, 6H, CH3).

EXAMPLE 15

[0292] 4-[3-[2-[4-(2-Methoxybenzoyl)piperazin-1-yl]ethyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile

[0293] 15a) 1,1-Dimethylethyl 4-[2-[3-[4-cyano-3-(trifluoromethyl)phenyl]-4-imino-5,5-dimethyl-2-thioxoimidazolidin-1-yl]ethyl]piperazine-1-carboxylate

[0294] 687 g of 4-amino-2-(trifluoromethyl)benzonitrile with 311 μl of thiophosgene in 4 ml of N,N-dimethylformamide was stirred for one hour at room temperature under nitrogen atmosphere. The reaction mixture was diluted with ethyl acetate, washed with water and then concentrated by evaporation in a vacuum. The thus obtained crude isothiocyanate was combined with the cyanoamine that was produced and filtered by two hours of stirring from 743 μl of acetone cyanohydrin with 930 mg of 1,1-dimethylethyl 4-(2-aminoethyl)piperazine-1-carboxylate and 406 mg of a molecular sieve 3 Å in 20 ml of tetrahydrofuran at room temperature, and it was heated to boiling for one hour with 0.57 ml of triethylamine in 40 ml of tetrahydrofuran. After concentration by evaporation in a vacuum, the title compound was obtained as a crude product, which was immediately further reacted.

[0295] 15b) 1,1-Dimethylethyl 4-[2-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]ethyl]piperazine-1-carboxylate

[0296] The crude product that was produced under 15a was stirred with 3.7 ml of 4 molar aqueous hydrochloric acid in 40 ml of methanol overnight at room temperature. The reaction mixture was then poured onto saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic phase was washed with saturated aqueous sodium chloride solution, dried on sodium sulfate, filtered and concentrated by evaporation in a vacuum. Column chromatography on silica gel with a mixture that consists of hexane/ethyl acetate yields 553 mg of the title compound as a colorless foam.

[0297] 1 H-NMR (300 MHz, CDCl3): δ [ppm]=7.95 d (J=8 Hz, 1H, aryl); 7.88 d (J=2 Hz, 1H, aryl); 7.77 ddbr (J=8 Hz+2 Hz, 1H, aryl); 3.85 m (2H, CH2N); 3.44 m (4H, piperazine); 2.78 m (2H, CH2N); 2.52 m (4H, piperazine); 1.59 s (6H, CH3); 1.46 m (9H, tBu).

[0298] 15c) 4-[4,4-Dimethyl-5-oxo-3-[2-(piperazin-1-yl)ethyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile

[0299] 553 mg of the compound, produced under 15b, was stirred with 809 μl of trifluoroacetic acid in 10 ml of dichloromethane for 24 hours at room temperature. The reaction mixture was concentrated by evaporation in a vacuum and concentrated by evaporation in a vacuum several times with toluene, taken up in methanol, set at a pH of 8 to 9 with anion exchanger (Bio-Rad AG 1-X8, OH form), filtered and concentrated by evaporation in a vacuum. 426 mg of the title compound was obtained as a crude product, which was further reacted in this form.

[0300] 1 H-NMR (300 MHz, CDCl3): δ [ppm]=7.95 d (J=8 Hz, 1H, aryl); 7.89 d (J=2 Hz, 1H, aryl); 7.77 ddbr (J=8 Hz+2 Hz, 1H, aryl); 3.85 m (2H, CH2N); 2.91 m (4H, piperazine); 2.76 m (2H, CH2N); 2.55 m (4H, piperazine); 1.59 s (6H, CH3).

[0301] 15d) 4-[3-[2-[4-(2-Methoxybenzoyl)piperazin-1-yl]ethyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile

[0302] 20 mg of the compound that was produced under 15c was refluxed with 14 ml of 2-methoxybenzoyl chloride and 13.1 μl of triethylamine in 1 ml of tetrahydrofuran for 4 hours. The reaction mixture was concentrated by evaporation in a vacuum. Column chromatography on silica gel with a mixture that consists of hexane/ethyl acetate yields 16 mg of the title compound as a colorless oil.

[0303] 1 H-NMR (300 MHz, CDCl3): δ [ppm]=7.95 d (J=8 Hz, 1H, aryl); 7.88 d (J=2 Hz, 1H, aryl); 7.76 ddbr (J=8 Hz+2 Hz, 1H, aryl); 7.35 ddd (J=8 Hz+7 Hz+2 Hz, 1H, aryl); 7.23 dd (J=7 Hz+2 Hz, 1H, aryl); 6.99 dd (J=7 Hz+7 Hz, 1H, aryl); 6.91 dbr (J=8 Hz, 1H, aryl); 3.85 m (2H, CH2N); 3.84 m (1H, piperazine); 3.83 s (3H, OCH3); 3.81 m (1H, piperazine); 3.28 m (2H, piperazine); 2.80 m (2H, CH2N); 2.67 m (1H, piperazine); 2.60 m (1H, piperazine); 2.55 m (1H, piperazine); 2.47 m (1H, piperazine); 1.59 s (6H, CH3).

[0304] The following compounds according to the invention were produced analogously to the previously described compounds.

TABLE 5
Compounds of General Formula I According to the Invention, in which
V = Trifluoromethylbenzonitrile, W = Maleimide, n = 1
		Synthesis
		Analogous
Ex-		to	ESI-
ample	Name	Example	MS
16	4-[3-[(4-Acetylpiperazin-1-yl)methyl]-	8	420
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-
	1-yl]-2-(trifluoromethyl)benzonitrile
17	4-[2,5-Dihydro-3-[[4-(methoxy-	8	450
	acetyl)piperazin-1-yl]methyl]-4-methyl-
	2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
18	4-[2,5-Dihydro-3-[4-[[(2-methoxyethoxy)-	8	494
	acetyl]piperazin-1-yl]methyl]-4-
	methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
19	4-[2,5-Dihydro-3-[[4-[[2-(2-	8	538
	methoxyethoxy)-ethoxy]acetyl]piperazin-
	1-yl]methyl]-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
20	4-[2,5-Dihydro-3-[[4-(2-methoxybenzoyl)-	8	512
	piperazin-1-yl]methyl]-4-methyl-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzo-
	nitrile
21	4-[2,5-Dihydro-3-methyl-4-[[4-	8	456
	(methylsulfonyl)-piperazin-1-yl]methyl]-2,
	5-dioxo-1H-pyrrol-1-yl]-
	2-(trifluoromethyl)benzonitrile
22	4-[3-[[4-(Ethylsulfonyl)piperazin-1-	8	470
	yl]methyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
23	4-[2,5-Dihydro-3-[[4-(2-methoxy-	8	500
	ethyl)sulfonyl]-piperazin-1-yl]methyl]-4-
	methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
24	4-[2,5-Dihydro-3-[[4-[[2-[2-(2-	8	588
	methoxyethoxy)-ethoxy]-
	ethyl]sulfonyl]piperazin-1-yl]methyl]-4-
	methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
25	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[[4-	8	518
	(phenylsulfonyl)piperazin-1-yl]methyl]-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile

[0305]

TABLE 6
Compounds of General Formula I According to the Invention, in which
V = Trifluoromethylbenzonitrile, W = Maleimide, n = 2
		Synthesis
		Analogous
Ex-		to	ESI-
ample	Name	Example	MS
26	4-[3-[2-(4-Acetylpiperazin-1-yl)ethyl]-	7 (4)	434
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-
	1-yl]-2-(trifluoromethyl)benzonitrile
27	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[2-	7 (4)	448
	(4-(1-oxopropyl)piperazin-1-yl)ethyl]-
	1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
28	4-[3-[2-[4-(Cyclopropylcarbonyl)piperazin-1-	7 (4)	460
	yl]ethyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
29	4-[2,5-Dihydro-3-[2-[4-	7 (4)	464
	(methoxyacetyl)piperazin-1-
	yl]ethyl]-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
30	4-[2,5-Dihydro-3-[2-[4-(3-methoxy-1-	7 (4)	478
	oxopropyl)piperazin-1-yl]ethyl]-4-
	methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)-benzonitrile
31	4-[2,5-Dihydro-3-[2-[4-[(2-methoxyethoxy)-	7 (4)	508
	acetyl]piperazin-1-yl]ethyl]-4-methyl-
	2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
32	4-[2,5-Dihydro-3-[2-[4-[[2-(2-	7 (4)	552
	methoxyethoxy)-ethoxy]acetyl]piperazin-1-
	yl]ethyl]-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
33	4-[2,5-Dihydro-3-[2-[4-(2-methoxybenzoyl)-	7 (4)	526
	piperazin-1-yl]ethyl]-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
34	4-[2,5-Dihydro-3-methyl-4-	7	470
	[2-[4-(methylsulfonyl)-piperazin-
	1-yl]ethyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
35	4-[3-[2-[4-(Ethylsulfonyl)piperazin-	7	484
	1-yl]ethyl]-2,5-dihydro-4-methyl-
	2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
36	4-[3-[2-[4-(Cyclopropylsulfonyl)piperazin-1-	7	496
	yl]ethyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
37	4-[2,5-Dihydro-3-[2-[4-(2-methoxyethyl)-	7	514
	sulfonyl]piperazin-1-yl]ethyl]-4-methyl-
	2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)benzonitrile
38	4-[2,5-Dihydro-3-[2-[4-[[2-	7	558
	(2-methoxyethoxy)-ethyl]sulfonyl]piperazin-
	1-yl]ethyl]-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
39	4-[2,5-Dihydro-3-[2-[4-[[2-	7	602
	[2-(2-methoxyethoxy)-
	ethoxy]ethyl]sulfonyl]piperazin-1-
	yl]ethyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-
	yl]-2-(trifluoromethyl)benzonitrile
40	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[2-[4-	7	532
	(phenylsulfonyl)piperazin-1-yl]ethyl]-
	1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)benzonitrile
41	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[2-[4-	7	546
	[(phenylmethyl)sulfonyl]piperazin-1-
	yl]ethyl]-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
42	4-[2,5-Dihydro-3-methyl-4-[2-[4-	7	536
	[(1-methyl-1H-imidazol-4-
	yl)sulfonyl]piperazin-1-yl]ethyl]-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
43	4-[2-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	7 (6)	477
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]ethyl]-N-(1-methylethyl)piperazine-
	1-carboxamide
44	4-[2-[1-[4-Cyano-3-(trifluoro-	7 (12)	479
	methyl)phenyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-3-yl]ethyl]-
	N-ethylpiperazine-1-carbothioamide
45	Methyl 4-[2-[1-[4-cyano-3-(trifluoromethyl)-	7 (13)	450
	phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-3-yl]ethyl]piperazine-1-carboxylate
46	S-Methyl 4-[2-[1-[4-cyano-3-	7 (13)	466
	(trifluoromethyl)-phenyl]-2,5-dihydro-4-
	methyl-2,5-dioxo-1H-pyrrol-3-
	yl]ethyl]piperazine-1-carbothioate
47	4-[2-[1-[4-Cyano-3-(trifluoro-	7	499
	methyl)phenyl]-2,5-dihydro-4-methyl-
	2,5-dioxo-1H-pyrrol-3-yl]ethyl]-
	N,N-dimethylpiperazine-1-sulfonamide

[0306]

TABLE 7
Compounds of General Formula I According to the Invention, in which
V = Trifluoromethylbenzonitrile, W = Maleimide, n = 3
		Synthesis
		Analogous
Ex-		to	ESI-
ample	Name	Example	MS
48	4-[3-[3-(4-Acetylpiperazin-1-yl)propyl]-	7 (4)	448
	2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
49	4-[2,5-Dihydro-3-methyl-2,5-dioxo-	7 (4)	462
	4-[3-(4-(1-oxopropyl)-piperazin-1-
	yl)propyl]-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)-benzonitrile
50	4-[3-[3-[4-(Cyclopropyl-	7 (4)	474
	carbonyl)piperazin-1-yl]-propyl]-2,5-
	dihydro-4-methyl-2,5-dioxo-1H-pyrrol-
	l-yl]-2-(trifluoromethyl)benzonitrile
51	4-[2,5-Dihydro-3-[3-[4-	7 (4)	478
	(methoxyacetyl)piperazin-1-yl]-propyl]-
	4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-
	2-(trifluoromethyl)benzonitrile
52	4-[2,5-Dihydro-3-[3-[4-(3-methoxy-	7 (4)	492
	1-oxopropyl)-piperazin-1-yl]propyl]-4-
	methyl-2,5-dioxo-1H-pyrrol-1-yl]-
	2-(trifluoromethyl)benzonitrile
53	4-[2,5-Dihydro-3-[3-[4-[(2-methoxyethoxy)-	7 (4)	522
	acetyl]piperazin-1-yl]propyl]-
	4-methyl-2,5-dioxo-1H-pyrrol-1-
	yl]-2-(trifluoromethyl)benzonitrile
54	4-[2,5-Dihydro-3-[3-[4-[[2-(2-	7 (4)	566
	methoxyethoxy)-ethoxy]-acetyl]piperazin-
	1-yl]propyl]-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
55	4-[2,5-Dihydro-3-[3-[4-(2-methoxybenzoyl)-	7 (4)	540
	piperazin-1-yl]-propyl]-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
56	4-[2,5-Dihydro-3-methyl-4-[3-[4-	7	484
	(methylsulfonyl)-piperazin-1-yl]propyl]-2,
	5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)-benzonitrile
57	4-[3-[3-[4-(Ethylsulfonyl)piperazin-	7	498
	1-yl]propyl]-2,5-dihydro-4-methyl-2,
	5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)-benzonitrile
58	4-[3-[3-[4-(Cyclopropylsulfonyl)piperazin-1-	7	510
	yl]propyl]-2,5-dihydro-4-methyl-
	2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
59	4-[2,5-Dihydro-3-[3-[4-(2-methoxyethyl)-	7	528
	sulfonyl]piperazin-1-yl]propyl]-4-
	methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)-benzonitrile
60	4-[2,5-Dihydro-3-[3-[4-[[2-	7	572
	(2-methoxyethoxy)-ethoxy]ethyl]-
	sulfonyl]piperazin-1-yl]propyl]-4-
	methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)-benzonitrile
61	4-[2,5-Dihydro-3-[3-[4-[[2-[2-	7	616
	(2-methoxyethoxy)-ethoxy]-
	ethyl]sulfonyl]piperazin-1-yl]propyl]-4-
	methyl-2,5-dioxo-1H-pyyrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
62	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[3-[4-	7	546
	(phenyl-sulfonyl)piperazin-1-yl]propyl]-
	1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
63	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[3-[4-	7	560
	[(phenylmethyl)-sulfonyl]piperazin-
	1-yl]propyl]-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
64	4-[2,5-Dihydro-3-methyl-4-[3-[4-	7	550
	[(1-methyl-1H-imidazol-4-
	yl)sulfonyl]piperazin-1-yl]propyl]-
	2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)-benzonitrile
65	4-[3-[1-[4-Cyano-3-(trifluoro-	7 (6)	491
	methyl)phenyl]-2,5-dihydro-4-methyl-
	2,5-dioxo-1H-pyrrol-3-yl]propyl]-N-
	(1-methylethyl)-piperazine-1-carboxamide
66	4-[3-[l-[4-Cyano-3-(trifluoromethyl)phenyl]-	7 (12)	493
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]propyl]-N-ethylpiperazine-1-
	carbothioamide
67	Methyl 4-[3-[l-[4-cyano-3-(trifluoromethyl)-	7 (13)	464
	phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-3-yl]propyl]-piperazine-1-carboxylate
68	S-Methyl 4-[3-[1-[4-cyano-3-	7 (13)	480
	(trifluoromethyl)-phenyl]-2,5-dihydro-
	4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]propyl]-piperazine-1-carbothioate
69	4-[3-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	7	513
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]propyl]-N,N-dimethylpiperazine-
	1-sulfonamide

[0307]

TABLE 8
Compounds of General Formula I According to the Invention, in which
V = Trifluoromethylbenzonitrile, W = Maleimide, n = 4
		Synthesis
		Anal-
Ex-		ogous
am-		to	ESI-
ple	Name	Example	MS
70	1,1-Dimethylethyl 4-[4-[1-[4-cyano-3-	1	521
	(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-
	2,5-dioxo-1H-pyrrol-3-yl]-butyl]piperazine-1-
	carboxylate
71	4-[2,5-Dihydro-3-methyl-4-[4-[4-[2-	3	543
	(methylsulfanyl)-phenyl]piperazin-1-yl]butyl]-
	2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
72	4-[3-[4-[4-(3,5-Dichloropyridin-4-yl)piper-	3	566
	azin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)ben-
	zonitrile
73	4-[3-[4-[4-(Cyclopentylacetyl)piperazin-1-	4	531
	yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
74	4-[3-[4-[4-(2,6-Difluorobenzoyl)piperazin-1-	4	561
	yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
75	4-[3-[4-[4-(2,6-Dichlorobenzoyl)piperazin-1-	4	593
	yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
76	4-[3-[4-[4-(3-Fluorobenzoyl)piperazin-1-	4	543
	yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
77	4-[2,5-Dihydro-3-[4-[4-(3-methoxybenzoyl)-	4	555
	piperazin-1-yl]butyl]-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
78	4-[2,5-Dihydro-3-methyl-4-[4-[4-(3-	4	539
	methylbenzoyl)-piperazin-1-yl]butyl]-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)ben-
	zonitrile
79	4-[3-[4-[4-(4-Fluorobenzoyl)piperazin-1-	4	543
	yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
80	4-[2,5-Dihydro-3-methyl-4-[4-[4-[(naphthalen-	4	575
	1-yl)-carbonyl]piperazin-1-yl]butyl]-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
81	4-[2,5-Dihydro-3-methyl-4-[4-[4-[(naphthalen-	4	575
	2-yl)-carbonyl]piperazin-1-yl]butyl]-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
82	4-[3-[4-[4-(3-Cyanobenzoyl)piperazin-1-	4	550
	yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
83	4-[3-[4-[4-(Cyclohexylcarbonyl)piperazin-1-	4	531
	yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
84	4-[3-[4-[4-[(Furan-2-yl)carbonyl]piperazin-1-	4	515
	yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
85	4-[3-[4-[4-(Cyclopentylcarbonyl)piperazin-1-	4	517
	yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
86	4-[2,5-Dihydro-3-methyl-4-[4-[4-[(5-	4	530
	methylisoxazol-3-yl)carbonyl]piperazin-1-
	yl]butyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
87	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[4-[4-	4	539
	(phenyl-acetyl)piperazin-1-yl]butyl]-1H-pyrrol-
	1-yl]-2-(trifluoromethyl)benzonitrile
88	4-[2,5-Dihydro-3-[4-[4-(2-methoxybenzoyl)-	4	555
	piperazin-1-yl]butyl]-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
89	4-[2,5-Dihydro-3-[4-[4-(methoxyacetyl)piper-	4	492
	azin-1-yl]-butyl]-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
90	4-[3-[4-[4-(2-Chlorobenzoyl)piperazin-1-	4	559
	yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
91	4-[3-[4-[4-(2-Fluorobenzoyl)piperazin-1-	4	543
	yl]butyl]2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
92	4-[3-[4-(4-Benzoylpiperazin-1-yl)butyl]-2,5-	4	525
	dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)-benzonitrile
93	4-[3-[4-[4-(Cyclobutylcarbonyl)piperazin-1-	4	503
	yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
94	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[4-[4-	4	526
	[(pyridin-3-yl)carbonyl]piperazin-1-yl]butyl]-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
95	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[4-[4-	4	526
	[(pyridin-4-yl)carbonyl]piperazin-1-yl]butyl]-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
96	4-[3-[4-[4-[4-(Dimethylamino)benzoyl]piper-	4	568
	azin-1-yl]butyl-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)benzonitrile
97	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[4-[4-	4	571
	[(phenyl-sulfanyl)acetyl]piperazin-1-yl]butyl]-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
98	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[4-[4-	4	555
	(phenoxy-acetyl)piperazin-1-yl]butyl]-1H-
	pyrrol-1-yl)-2-(trifluoromethyl)benzonitrile
99	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[4-[4-	4	531
	[(thien-2-yl)-carbonyl]piperazin-1-yl]butyl]-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
100	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[4-[4-(3-	4	553
	phenyl-1-oxopropyl)piperazin-1-yl]butyl]-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
101	4-[3-[4-[4-[(1,3-Benzodioxol-5-yl)carbonyl]-	4	569
	piperazin-1-yl]-butyl]-2,5-dihydro-4-methyl-2,
	5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
102	4-[2,5-Dihydro-3-[4-[4-[(4-methoxyphenyl)-	4	569
	acetyl]piperazin-1-yl]butyl]-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)benzonitrile
103	4-[2,5-Dihydro-3-methyl-4-[4-[4-(2-	4	539
	methylbenzoyl)-piperazin-1-yl]butyl]-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)benzonitrile
104	4-[3-[4-[4-(4-Chlorobenzoyl)piperazin-1-	4	559
	yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
105	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[4-[4-	4	545
	[(thien-2-yl)-acetyl]piperazin-1-yl]butyl]-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
106	4-[3-[4-[4-(3-Chlorobenzoyl)piperazin-1-	4	559
	yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
107	4-[3-[4-[4-(4-Cyanobenzoyl)piperazin-1-	4	550
	yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
108	4-[2,5-Dihydro-3-[4-[4-(3-methoxy-1-	4	506
	oxopropyl)piperazin-1-yl]butyl]-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
109	4-[2,5-Dihydro-3-[4-[4-[(2-methoxyethoxy)-	4	536
	acetyl]piperazin-1-yl]butyl]-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)benzonitrile
110	4-[2,5-Dihydro-3-[4-[4-[[2-(2-methoxyethoxy)-	4	580
	ethoxy]-acetyl]piperazin-1-yl]butyl]-4-methyl-
	2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
111	4-[4-[4-[4-(Cyclopropylsulfonyl)piperazin-1-	5	524
	yl]butyl]-2,5-dihydro-3-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
112	4-[2,5-Dihydro-3-[4-[4-(2-methoxyethyl)-	5	542
	sulfonyl]piperazin-1-yl]butyl]-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)benzonitrile
113	4-[2,5-Dihydro-3-[4-[4-[[2-(2-	5	586
	methoxyethoxy)ethyl]-sulfonyl]piperazin-1-
	yl]butyl]-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
114	4-[2,5-Dihydro-3-[4-[4-[[2-[2-(2-methoxy-	5	630
	ethoxy)-ethoxy]-ethyl]sulfonyl]piperazin-1-
	yl]butyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-
	yl]-2-(trifluoromethyl)benzonitrile
115	4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,	5	527
	5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]butyl]-N,N-dimethylpiperazine-1-sulfon-
	amide
116	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[4-[4-	5	561
	(phenyl-sulfonyl)piperazin-1-yl]butyl]-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
117	4-[2,5-Dihydro-3-methyl-4-[4-[4-(methyl-	5	499
	sulfonyl)-piperazin-1-yl]butyl]-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
118	4-[2,5-Dihydro-3-methyl-4-[4-[4-[(4-	5	575
	methylphenyl)-sulfonyl]piperazin-1-yl]butyl]-2,
	5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
119	N-[4-[[4-[4-[1-[4-Cyano-3-(trifluoromethyl)-	5	618
	phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-3-yl]butyl]piperazin-1-yl]sulfonyl]-
	phenyl]acetamide
120	4-[3-[4-[4-[(4-Chlorophenyl)sulfonyl]piperazin-	5	595
	1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
121	4-[3-[4-[4-[(4-Cyanophenyl)sulfonyl]piperazin-	5	586
	1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
122	4-[2,5-Dihydro-3-methyl-4-[4-[4-[(naphthalen-	5	611
	2-yl)-sulfonyl]piperazin-1-yl]butyl]-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
123	4-[3-[4-[4-[(Quinolin-8-yl)sulfonyl]piperazin-1-	5	612
	yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
124	4-[3-[4-[4-[(2-Cyanophenyl)sulfonyl]piperazin-	5	586
	1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
125	4-(3-[4-[4-[(3-Cyanophenyl)sulfonyl]piperazin-	5	586
	1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
126	4-[3-[4-[4-[(3,5-Dimethylisoxazol-4-yl)sul-	5	580
	fonyl]-piperazin-1-yl]butyl]-2,5-dihydro-4-
	methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
127	4-[3-[4-[4-[(5-Chloro-1,3-dimethyl-1H-pyrazol-	5	613
	4-yl)sulfonyl]piperazin-1-yl]butyl]-2,5-dihydro-
	4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
128	4-[2,5-Dihydro-3-methyl-4-[4-[4-[(1-methyl-	5	565
	1H-imidazol-4-yl)sulfonyl]piperazin-1-
	yl]butyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(tri-
	fluoromethyl)-benzonitrile
129	4-3-[4-[4-(Butylsulfonyl)piperazin-1-yl]butyl]-	5	541
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-
	yl]-2-(trifluoromethyl)-benzonitrile
130	4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,	6	540
	5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]butyl]-N-phenylpiperazine-1-carboxamide
131	4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,	6	590
	5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]butyl]-N-(naphthalen-1-yl)-piperazine-1-
	carboxamide
132	4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,	6	590
	5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]butyl]-N-(naphthalen-2-yl)-piperazine-1-
	carboxamide
133	N-(2-Chlorophenyl)-4-[4-[1-[4-cyano-3-	6	574
	(trifluoromethyl)-phenyl]-2,5-dihydro-4-
	methyl-2,5-dioxo-1H-pyrrol-3-yl]-butyl]piper-
	azine-1-carboxamide
134	4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	608
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]butyl]-N-[2-(trifluoromethyl)-phenyl]piper-
	azine-1-carboxamide
135	4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	570
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]butyl]-N-(3-methoxy-phenyl)piperazine-1-
	carboxamide
136	N-(4-Chlorophenyl)-4-[4-[1-[4-cyano-3-	6	574
	(trifluoromethyl)-phenyl]-2,5-dihydro-4-
	methyl-2,5-dioxo-1H-pyrrol-3-yl]-butyl]piper-
	azine-1-carboxamide
137	4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	632
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]butyl]-N-(4-phenoxy-phenyl)piperazine-1-
	carboxamide
138	4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	586
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]butyl]-N-[4-(methylsulfanyl)phenyl]piper-
	azine-1-carboxamide
139	N-([1,1′-Biphenyl]-2-yl)-4-[4-[1-[4-cyano-3-	6	616
	(trifluoromethyl)-phenyl]-2,5-dihydro-4-
	methyl-2,5-dioxo-1H-pyrrol-3-yl]-butyl]piper-
	azine-1-carboxamide
140	4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	600
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]butyl]-N-(2,5-dimethoxyphenyl)piperazine-
	1-carboxamide
141	4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	582
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]butyl]-N-[2-(1-methylethyl)phenyl]pipera-
	zine-1-carboxamide
142	4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	582
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]butyl]-N-(2,4,6-trimethylphenyl)pipera-
	zine-1-carboxamide
143	(R)-4-[4-[1-[4-Cyano-3-(trifluoro-	6	568
	methyl)phenyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-3-yl]butyl]-N-(1-phenylethyl)-
	piperazine-1-carboxamide
144	4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	596
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]butyl]-N-[2-(1,1-dimethylethyl)phenyl]pip-
	erazine-1-carboxamide
145	4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	548
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]butyl]-N-hexylpiperazine-1-carboxamide

[0308]

TABLE 9
Compounds of General Formula I According to the Invention, in which
V = Trifluoromethylbenzonitrile, W = Maleimide, n = 5
		Synthesis
		Anal-
Ex-		ogous
am-		to	ESI-
ple	Name	Example	MS
146	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-	3	513
	(pyrazin-2-yl)-piperazin-1-yl]pentyl]-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)-benzonitrile
147	4-[3-[5-[4-(2,4-Difluorophenyl)piperazin-1-	3	547
	yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
148	4-[3-[5-[4-[(Furan-2-yl)carbonyl]piperazin-1-	4	529
	yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
149	4-[2,5-Dihydro-3-methyl-4-[5-[4-[(5-	4	544
	methylisoxazol-3-yl)-carbonyl]piperazin-1-
	yl]pentyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
150	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-	4	553
	(phenylacetyl)-piperazin-1-yl]pentyl]-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)-benzonitrile
151	4-[2,5-Dihydro-3-[5-[4-(4-methoxybenzoyl)-	4	569
	piperazin-1-yl]-pentyl]-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
152	4-[2,5-Dihydro-3-[5-[4-(2-methoxybenzoyl)-	4	569
	piperazin-1-yl]-pentyl]-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
153	4-[2,5-Dihydro-3-[5-[4-(methoxyacetyl)piper-	4	507
	azin-1-yl]-pentyl]-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
154	4-[3-[5-[4-(2-Chlorobenzoyl)piperazin-1-	4	573
	yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
155	4-[3-[5-[4-(2-Fluorobenzoyl)piperazin-1-	4	557
	yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
156	4-[3-[5-(4-Benzoylpiperazin-1-yl)pentyl]-2,5-	4	539
	dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
157	4-[3-[5-[4-(Cyclobutylcarbonyl)piperazin-1-	4	517
	yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
158	4-[3-[5-[4-(3,4-Dimethoxybenzoyl)piperazin-1-	4	599
	yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
159	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-	4	540
	[(pyridin-3-yl)-carbonyl]piperazin-1-yl]pentyl]-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
160	4-[3-[5-[4-(Cyclopropylcarbonyl)piperazin-1-	4	503
	yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
161	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-	4	540
	[(pyridin-4-yl)-carbonyl]piperazin-1-yl]pentyl]-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
162	4-[3-[5-[4-[4-(Dimethylamino)benzoyl]piper-	4	582
	azin-1-yl]-pentyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)benzonitrile
163	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-	4	585
	[(phenylsulfanyl)acetyl]piperazin-1-yl]pentyl]-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
164	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-	4	569
	(phenoxyacetyl)piperazin-1-yl]pentyl]-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
165	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-	4	545
	[(thien-2-yl)-carbonyl]piperazin-1-yl]pentyl]-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
166	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-(3-	4	567
	phenyl-1-oxopropyl)piperazin-1-yl]pentyl]-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
167	4-[3-[5-[4-[(1,3-Benzodioxol-5-yl)carbonyl]-	4	583
	piperazin-1-yl]-pentyl]-2,5-dihydro-4-methyl-2,
	5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
168	4-[2,5-Dihydro-3-[5-[4-[(4-methoxyphenyl)-	4	583
	acetyl]piperazin-1-yl]pentyl]-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)benzonitrile
169	4-[2,5-Dihydro-3-methyl-4-[5-[4-(2-	4	553
	methylbenzoyl)-piperazin-1-yl]pentyl]-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)benzonitrile
170	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-	4	559
	[(thien-2-yl)-acetyl]piperazin-1-yl]pentyl]-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
171	4-[3-[5-[4-[(4-Chlorophenoxy)acetyl]piperazin-	4	603
	1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
172	4-[3-[5-[4-(3-Cyclopentyl-1-oxopropyl)piper-	4	559
	azin-1-yl]-pentyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)benzonitrile
173	4-[3-[5-[4-(3-Chlorobenzoyl)piperazin-1-	4	573
	yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
174	4-[3-[5-[4-(3,3-Dimethyl-1-oxobutyl)piper-	4	533
	azin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
175	4-[2,5-Dihydro-3-methyl-4-[5-[4-(3-methyl-1-	4	519
	oxobutyl)-piperazin-1-yl]pentyl]-2,5-dioxo-1H-
	pyrrol-1-yl)-2-(trifluoromethyl)benzonitrile
176	4-[2,5-Dihydro-4-methyl-2,5-dioxo-3-[5-[4-	4	583
	[(phenyl-methoxy)acetyl]piperazin-1-
	yl]pentyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
177	4-[3-[5-[4-(Cyclopentylacetyl)piperazin-1-	4	545
	yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
178	4-[3-[5-[4-(2,6-Difluorobenzoyl)piperazin-1-	4	575
	yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
179	4-[3-[5-[4-(2,6-Dichlorobenzoyl)piperazin-1-	4	607
	yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
180	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-[2-	4	607
	(trifluoromethyl)benzoyl]piperazin-1-
	yl]pentyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
181	4-[3-[5-[4-(3-Fluorobenzoyl)piperazin-1-	4	557
	yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
182	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-[3-	4	607
	(trifluoromethyl)benzoyl]piperazin-1-
	yl]pentyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
183	4-[2,5-Dihydro-3-methyl-4-[5-[4-(4-	4	553
	methylbenzoyl)-piperazin-1-yl]pentyl]-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
184	4-[2,5-Dihydro-3-methyl-4-[5-[4-[(naphthalen-	4	589
	1-yl)-carbonyl]piperazin-1-yl]pentyl]-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
185	4-[2,5-Dihydro-3-methyl-4-[5-[4-[(naphthalen-	4	589
	2-yl)-carbonyl]piperazin-1-yl]pentyl]-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
186	4-[3-[5-[4-(3-Cyanobenzoyl)piperazin-1-	4	564
	yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
187	4-[3-[5-[4-(Cyclohexylcarbonyl)piperazin-1-	4	545
	yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
188	4-[3-[5-(4-Acetylpiperazin-1-yl)pentyl]-2,5-	4	476
	dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)-benzonitrile
189	4-[2,5-Dihydro-3-[5-[4-(3-methoxy-1-	4	520
	oxopropyl)piperazin-1-yl]pentyl]-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
190	4-[2,5-Dihydro-3-[5-[4-[(2-methoxyethoxy)-	4	550
	acetyl]piperazin-1-yl]pentyl]-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
191	4-[2,5-Dihydro-3-[5-[4-[[2-(2-methoxyethoxy)-	4	594
	ethoxy]-acetyl]piperazin-1-yl]pentyl]-4-
	methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
192	4-[4-[5-[4-(Cyclopropylsulfonyl)piperazin-1-	5	538
	yl]pentyl]-2,5-dihydro-3-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
193	4-[2,5-Dihydro-3-[5-[4-(2-methoxyethyl)-	5	556
	sulfonyl]piperazin-1-yl]pentyl]-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
194	4-[2,5-Dihydro-3-[5-[4-[[2-(2-methoxyethoxy)-	5	600
	ethyl]-sulfonyl]piperazin-1-yl]pentyl]-4-methyl-
	2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
195	4-[2,5-Dihydro-3-[5-[4-[[2-[2-(2-methoxy-	5	644
	ethoxy)-ethoxy]-ethyl]sulfonyl]piperazin-1-
	yl]pentyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-
	yl]-2-(trifluoromethyl)benzonitrile
196	4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	5	541
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]pentyl]-N,N-dimethylpiperazine-1-sulfona-
	mide
197	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-[(1-	5	541
	methylethyl)-sulfonyl]piperazin-1-yl]pentyl]-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
198	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-	5	575
	(phenylsulfonyl)piperazin-1-yl]pentyl]-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
199	4-[2,5-Dihydro-3-methyl-4-[5-[4-	5	513
	(methylsulfonyl)piperazin-1-yl]pentyl]-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
200	4-[3-[5-[4-[(4-Chlorophenyl)sulfonyl]piperazin-	5	609
	1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
201	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-	5	589
	[(phenylmethyl)-sulfonyl]piperazin-1-
	yl]pentyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
202	4-[3-[5-[4-[(4-Cyanophenyl)sulfonyl]piper-	5	600
	azin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
203	4-[4-[5-[4-[(Quinolin-8-yl)sulfonyl]piperazin-1-	5	626
	yl]pentyl]-2,5-dihydro-3-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
204	4-[3-[5-[4-[(2-Fluorophenyl)sulfonyl]piperazin-	5	593
	1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
205	4-[3-[5-[4-[(2,5-Dimethoxyphenyl)sulfonyl]-	5	635
	piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-
	2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
206	4-[3-[5-[4-[(3-Cyanophenyl)sulfonyl]piperazin-	5	600
	1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
207	4-[3-[5-[4-[(2,1,3-Benzothiadiazol-4-	5	633
	yl)sulfonyl]piperazin-1-yl]pentyl]-2,5-dihydro-
	4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
208	4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	534
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]pentyl]-N-(1,1-dimethyl-ethyl)piperazine-1-
	carboxamide
209	4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	604
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]pentyl]-N-(naphthalen-1-yl)piperazine-1-
	carboxamide
210	N-(4-Cyanophenyl)-4-[5-[1-[4-cyano-3-	6	579
	(trifluoromethyl)-phenyl]-2,5-dihydro-4-
	methyl-2,5-dioxo-1H-pyrrol-3-yl]-pentyl]piper-
	azine-1-carboxamide
211	N-(2-Chlorophenyl)-4-[5-[1-[4-cyano-3-	6	588
	(trifluoromethyl)-phenyl]-2,5-dihydro-4-
	methyl-2,5-dioxo-1H-pyrrol-3-yl]-pen-
	tyl]piperazine-1-carboxamide
212	4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	622
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]pentyl]-N-[2-(trifluoromethyl)phenyl]piper-
	azine-1-carboxamide
213	4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	568
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]pentyl]-N-(2-methyl-phenyl)piperazine-1-
	carboxamide
214	4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	568
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]pentyl]-N-(3-methyl-phenyl)piperazine-1-
	carboxamide
215	4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	572
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]pentyl]-N-(4-fluorophenyl)-piperazine-1-
	carboxamide
216	4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	584
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]pentyl]-N-(4-methoxy-phenyl)piperazine-1-
	carboxamide
217	N-(3-Cyanophenyl)-4-[5-[1-[4-cyano-3-	6	579
	(trifluoromethyl)-phenyl]-2,5-dihydro-4-
	methyl-2,5-dioxo-1H-pyrrol-3-yl]-pentyl]piper-
	azine-1-carboxamide
218	4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	614
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]pentyl]-N-(3,5-dimethoxy-phenyl)pipera-
	zine-1-carboxamide
219	4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	582
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]pentyl]-N-(2-phenylethyl)-piperazine-1-
	carboxamide
220	N-([1,1′-Biphenyl]-2-yl)-4-[5-[1-[4-cyano-3-	6	630
	(trifluoromethyl)-phenyl]-2,5-dihydro-4-
	methyl-2,5-dioxo-1H-pyrrol-3-yl]-pen-
	tyl]piperazine-1-carboxamide
221	4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	596
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]pentyl]-N-[2-(1-methyl-ethyl)phenyl]piper-
	azine-1-carboxamide
222	4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	623
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]pentyl]-N-(2,6-dichloropyridin-4-yl)piper-
	azine-1-carboxamide
223	(R)-4-[5-[1-[4-Cyano-3-(trifluoro-	6	582
	methyl)phenyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-3-yl]pentyl]-N-(1-phenylethyl)
	piperazine-1-carboxamide
224	4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	654
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]pentyl]-N-[3-[(trifluoromethyl)sulfanyl]-
	phenyl]piperazine-1-carboxamide
225	4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	582
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]pentyl]-N-[(3-methylphenyl)methyl]piper-
	azine-1-carboxamide
226	4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	598
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]pentyl]-N-[(4-methoxy-phenyl)methyl]-
	piperazine-1-carboxamide
227	4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	590
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]pentyl]-N-(1,1,3,3-tetramethylbutyl)piper-
	azine-1-carboxamide

[0309]

TABLE 10
Compounds of General Formula I According to the Invention, in which
V = Trifluoromethylbenzonitrile, W = Maleimide, n = 6
		Synthesis
		Anal-
Ex-		ogous
am-		to	ESI-
ple	Name	Example	MS
228	1,1-Dimethylethyl 4-[6-[1-[4-cyano-3-	1	549
	(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-
	2,5-dioxo-1H-pyrrol-3-yl]hexyl]-piperazine-1-
	carboxylate
229	4-[2,5-Dihydro-3-methyl-4-[6-(4-methylpiper-	3	463
	azin-1-yl)hexyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)-benzonitrile
230	Ethyl 4-[6-[1-[4-cyano-3-(trifluoro-	3	521
	methyl)phenyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-3-yl]hexyl]piperazine-1-
	carboxylate
231	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-	3	526
	(pyridin-2-yl)piperazin-1-yl]hexyl]-1H-pyrrol-
	1-yl]-2-(trifluoromethyl)-benzonitrile
232	(Phenylmethyl) 4-[6-[1-[4-cyano-3-	3	583
	(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-
	2,5-dioxo-1H-pyrrol-3-yl]hexyl]-piperazine-1-
	carboxylate
233	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-	3	527
	(pyrimidin-2-yl)-piperazin-1-yl]hexyl]-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)-benzonitrile
234	4-[2,5-Dihydro-3-[6-[4-(2-methoxyphenyl)-	3	555
	piperazin-1-yl]-hexyl]-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
235	4-[2,5-Dihydro-3-methyl-4-[6-[4-(2-	3	570
	nitrophenyl)piperazin-1-yl]hexyl]-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)-benzonitrile
236	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-	3	527
	(pyrazin-2-yl)-piperazin-1-yl]hexyl]-1H-pyrrol-
	1-yl]-2-(trifluoromethyl)-benzonitrile
237	4-[2,5-Dihydro-3-methyl-4-[6-[4-[2-	3	571
	(methylsulfanyl)-phenyl]piperazin-1-yl]hexyl]-
	2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
238	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-[3-	3	594
	(trifluoromethyl)pyridin-2-yl]piperazin-1-
	yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
239	4-[2,5-Dihydro-3-[6-[4-(2-methoxyethyl)piper-	3	507
	azin-1-yl]-hexyl]-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
240	4-[3-[6-[4-(3,5-Dichloropyridin-4-yl)piperazin-	3	594
	1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
241	4-[3-[6-(4-Acetylpiperazin-1-yl)hexyl]-2,5-	4	491
	dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)-benzonitrile
242	4-[3-[6-[4-[(Furan-2-yl)carbonyl]piperazin-1-	4	543
	yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
243	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-	4	547
	[(tetrahydrofuran-2-yl)carbonyl]piperazin-1-
	yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
244	4-[3-[6-[4-(Cyclopentylcarbonyl)piperazin-1-	4	545
	yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
245	4-[2,5-Dihydro-3-methyl-4-[6-[4-[(5-	4	558
	methylisoxazol-3-yl)-carbonyl]piperazin-1-
	yl]hexyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
246	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-	4	567
	(phenylacetyl)-piperazin-1-yl]hexyl]-1H-pyrrol-
	1-yl]-2-(trifluoromethyl)-benzonitrile
247	4-[2,5-Dihydro-3-[6-[4-(4-methoxybenzoyl)-	4	583
	piperazin-1-yl]-hexyl]-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
248	4-[2,5-Dihydro-3-[6-[4-(2-methoxybenzoyl)-	4	583
	piperazin-1-yl]-hexyl]-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
249	4-[2,5-Dihydro-3-[6-[4-(methoxyacetyl)piper-	4	521
	azin-1-yl]-hexyl]-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
250	4-[3-[6-[4-(2-Chlorobenzoyl)piperazin-1-	4	587
	yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
251	4-[3-[6-[4-(2-Fluorobenzoyl)piperazin-1-	4	571
	yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
252	4-[3-[6-(4-Benzoylpiperazin-1-yl)hexyl]-2,5-	4	553
	dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
253	4-[3-[6-[4-(Cyclobutylcarbonyl)piperazin-1-	4	531
	yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
254	4-[3-[6-[4-(3,4-Dimethoxybenzoyl)piperazin-1-	4	613
	yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
255	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-	4	599
	[(phenylsulfanyl)acetyl]piperazin-1-yl]hexyl]-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
256	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-	4	583
	(phenoxyacetyl)piperazin-1-yl]hexyl]-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
257	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-	4	559
	[(thien-2-yl)-carbonyl]piperazin-1-yl]hexyl]-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
258	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-(3-	4	581
	phenyl-1-oxopropyl)piperazin-1-yl]hexyl]-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
259	4-[3-[6-[4-[(1,3-Benzodioxol-5-yl)carbonyl]-	4	597
	piperazin-1-yl]-hexyl]-2,5-dihydro-4-methyl-
	2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
260	4-[2,5-Dihydro-3-[6-[4-[(4-methoxyphenyl)-	4	597
	acetyl]piperazin-1-yl]hexyl]-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
261	4-[2,5-Dihydro-3-methyl-4-[6-[4-(2-	4	567
	methylbenzoyl)-piperazin-1-yl]hexyl]-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
262	4-[3-[6-[4-(4-Chlorobenzoyl)piperazin-1-	4	587
	yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
263	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-	4	573
	[(thien-2-yl)-acetyl]piperazin-1-yl]hexyl]-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
264	4-[3-[6-[4-[(4-Chlorophenoxy)acetyl]piperazin-	4	617
	1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
265	4-[3-[6-[4-(3-Cyclopentyl-1-oxopropyl)piper-	4	573
	azin-1-yl]-hexyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
266	4-[3-[6-[4-(3-Chlorbenzoyl)piperazin-1-	4	587
	yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
267	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-[4-	4	621
	(trifluoromethyl)benzoyl]piperazin-1-yl]hexyl]-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
268	4-[3-[6-[4-(4-cyanobenzoyl)piperazin-1-	4	578
	yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
269	4-[3-[6-[4-(3,3-Dimethyl-1-oxobutyl)piperazin-	4	547
	1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
270	4-[2,5-Dihydro-3-methyl-4-[6-[4-(3-methyl-1-	4	533
	oxobutyl)-piperazin-1-yl]hexyl]-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
271	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-	4	597
	[(phenyl-methoxy)acetyl]piperazin-1-yl]hexyl]-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
272	4-[3-[6-[4-(Cyclopentylacetyl)piperazin-1-	4	559
	yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
273	4-[3-[6-[4-(2,6-Difluorobenzoyl)piperazin-1-	4	589
	yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
274	4-[3-[6-[4-(2,6-Dichlorobenzoyl)piperazin-1-	4	621
	yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
275	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-[2-	4	621
	(trifluoromethyl)benzoyl]piperazin-1-yl]hexyl]-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
276	4-[3-[6-[4-(3-Fluorobenzoyl)piperazin-1-	4	571
	yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
277	4-[2,5-Dihydro-3-[6-[4-(3-methoxybenzoyl)-	4	583
	piperazin-1-yl]-hexyl]-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
278	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-[3-	4	621
	(trifluoromethyl)benzoyl]piperazin-1-yl]hexyl]-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
279	4-[2,5-Dihydro-3-methyl-4-[6-[4-(3-	4	567
	methylbenzoyl)-piperazin-1-yl]hexyl]-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
280	4-[3-[6-[4-(4-Fluorobenzoyl)piperazin-1-	4	571
	yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
281	4-[2,5-Dihydro-3-methyl-4-[6-[4-(4-	4	567
	methylbenzoyl)-piperazin-1-yl]hexyl]-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
282	4-[2,5-Dihydro-3-methyl-4-[6-[4-[(naphthalen-	4	603
	1-yl)-carbonyl]piperazin-1-yl]hexyl]-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
283	4-[2,5-Dihydro-3-methyl-4-[6-[4-[(naphthalen-	4	603
	2-yl)-carbonyl]piperazin-1-yl]hexyl]-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
284	4-[3-[6-[4-(3-Cyanobenzoyl)piperazin-1-	4	578
	yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
285	4-[3-[6-[4-(Cyclohexylcarbonyl)piperazin-1-	4	559
	yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
286	4-[3-[6-[4-[[4-(1,1-Dimethylethyl)phenoxy]ace-	4	639
	tyl]-piperazin-1-yl]hexyl]-2,5-dihydro-4-
	methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
287	4-[2,5-Dihydro-3-[6-[4-(3-methoxy-1-	4	534
	oxopropyl)piperazin-1-yl]hexyl]-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
288	4-[2,5-Dihydro-3-[6-[4-[(2-methoxyethoxy)-	4	564
	acetyl]piperazin-1-yl]hexyl]-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
289	4-[2,5-Dihydro-3-[6-[4-[[2-(2-methoxyethoxy)-	4	608
	ethoxy]-acetyl]piperazin-1-yl]hexyl]-4-methyl-
	2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
290	4-[4-[6-[4-(Cyclopropylsulfonyl)piperazin-1-	5	552
	yl]hexyl]-2,5-dihydro-3-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
291	4-[2,5-Dihydro-3-[6-[4-(2-methoxyethyl)-	5	570
	sulfonyl]piperazin-1-yl]hexyl]-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
292	4-[2,5-Dihydro-3-[6-[4-[[2-(2-methoxyethoxy)-	5	614
	ethyl]-sulfonyl]piperazin-1-yl]hexyl]-4-methyl-
	2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
293	4-[2,5-Dihydro-3-[6-[4-[[2-[2-(2-methoxy-	5	658
	ethoxy)-ethoxy]-ethyl]sulfonyl]piperazin-1-
	yl]hexyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-
	yl]-2-(trifluoromethyl)benzonitrile
294	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	5	555
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N,N-dimethylpiperazine-1-sulfona-
	mide
295	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-	5	589
	(phenyl-sulfonyl)piperazin-1-yl]hexyl]-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
296	4-[2,5-Dihydro-3-methyl-4-[6-[4-(methyl-	5	527
	sulfonyl)-piperazin-1-yl]hexyl]-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
297	4-[2,5-Dihydro-3 -methyl-4-[6-[4-[(4-	5	603
	methylphenyl)-sulfonyl]piperazin-1-yl]hexyl]-
	2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
298	N-[4-[[4-[6-[1-[4-Cyano-3-(trifluoromethyl)-	5	646
	phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-3-yl]hexyl]piperazin-1-yl]sulfonyl]-
	phenyl]acetamide
299	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-	5	603
	[(phenylmethyl)-sulfonyl]piperazin-1-yl]hexyl]-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
300	4-[3-[6-[4-[(4-Cyanophenyl)sulfonyl]piper-	5	614
	azin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
301	4-[2,5-Dihydro-3-methyl-4-[6-[4-[(naphthalen-	5	639
	2-yl)-sulfonyl]piperazin-1-yl]hexyl]-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
302	4-[3-[6-[4-[[5-(Dimethylamino)naphthalen-	5	682
	1-yl]-sulfonyl]piperazin-1-yl]hexyl]-2,5-
	dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
303	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-	5	595
	[(thien-2-yl)-sulfonyl]piperazin-1-yl]hexyl]-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
304	4-[3-[6-[4-[(Quinolin-8-yl)sulfonyl]piperazin-1-	5	640
	yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
305	4-[3-[6-[4-[(2-Fluorophenyl)sulfonyl)piper-	5	607
	azin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
306	4-[3-[6-[4-[(2-Chlorophenyl)sulfonyl]piper-	5	623
	azin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
307	4-[3-[6-[4-[(2-Cyanophenyl)sulfonyl]piper-	5	614
	azin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
308	4-[3-[6-[4-[(3-Cyanophenyl)sulfonyl]piper-	5	614
	azin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
309	4-[2,5-Dihydro-3-methyl-4-[6-[4-[[5-[2-	5	743
	methyl-5-(trifluoromethyl)-2H-pyrazol-3-
	yl]thien-2-yl]sulfonyl]-piperazin-1-yl]hexyl]-
	2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
310	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-	5	740
	[[1,2,3,4-tetrahydro-2-(trifluoroacetyl)
	isoquinolin-7-yl]sulfonyl]-piperazin-1-
	yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)
	benzonitrile
311	4-[3-[6-[4-[(3,5-Dimethylisoxazol-4-	5	608
	yl)sulfonyl]piperazin-1-yl]hexyl]-2,5-dihydro-
	4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
312	4-[3-[6-[4-[(5-Chloro-1,3-dimethyl-1H-	5	641
	pyrazol-4-yl)sulfonyl]-piperazin-1-yl]hexyl]-
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-
	yl]-2-(trifluoromethyl)benzonitrile
313	4-[2,5-Dihydro-3-methyl-4-[6-[4-[(1-methyl-	5	593
	1H-imidazol-4-yl)sulfonyl]piperazin-1-
	yl]hexyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(tri-
	fluoromethyl)-benzonitrile
314	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	548
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(1,1-dimethylethyl)piperazine-1-
	carboxamide
315	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	568
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-phenylpiperazine-1-
	carboxamide
316	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	618
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(naphthalen-1-yl)piperazine-1-
	carboxamide
317	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	618
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(naphthalen-2-yl)piperazine-1-
	carboxamide
318	N-(4-Cyanophenyl)-4-[6-[1-[4-cyano-3-	6	593
	(trifluoromethyl)-phenyl]-2,5-dihydro-4-
	methyl-2,5-dioxo-1H-pyrrol-3-yl]-hexyl]piper-
	azine-1-carboxamide
319	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	534
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(1-methylethyl)-piperazine-1-
	carboxamide
320	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	636
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[3-(trifluoromethyl)phenyl]pipera-
	zine-1-carboxamide
321	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	586
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(2-fluorophenyl)-piperazine-1-
	carboxamide
322	N-(2-Chlorophenyl)-4-[6-[1-[4-cyano-3-	6	602
	(trifluoromethyl)-phenyl]-2,5-dihydro-4-
	methyl-2,5-dioxo-1H-pyrrol-3-yl]-hexyl]pipera-
	zine-1-carboxamide
323	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	598
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(2-methoxy-phenyl)piperazine-1-
	carboxamide
324	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	636
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[2-(trifluoromethyl)phenyl]pipera-
	zine-1-carboxamide
325	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	582
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(2-methyl-phenyl)piperazine-1-
	carboxamide
326	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	586
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(3-fluorophenyl)-piperazine-1-
	carboxamide
327	N-(3-Chlorophenyl)-4-[6-[1-[4-cyano-3-	6	602
	(trifluoromethyl)-phenyl]-2,5-dihydro-4-
	methyl-2,5-dioxo-1H-pyrrol-3-yl]-hexyl]pipera-
	zine-1-carboxamide
328	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	598
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(3-methoxy-phenyl)piperazine-1-
	carboxamide
329	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	582
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(3-methylphenyl)piperazine-1-
	carboxamide
330	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	586
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(4-fluorophenyl)-piperazine-1-
	carboxamide
331	N-(4-Chlorophenyl)-4-[6-[1-[4-cyano-3-	6	602
	(trifluoromethyl)-phenyl]-2,5-dihydro-4-
	methyl-2,5-dioxo-1H-pyrrol-3-yl]-hexyl]pipera-
	zine-1-carboxamide
332	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	598
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(4-methoxy-phenyl)piperazine-1-
	carboxamide
333	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	636
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[4-(trifluoromethyl)phenyl]pipera-
	zine-1-carboxamide
334	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	582
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(4-methylphenyl)piperazine-1-
	carboxamide
335	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	532
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(prop-2-enyl)-piperazine-1-
	carboxamide
336	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	574
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-cyclohexyl-piperazine-1-
	carboxamide
337	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	582
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(phenylmethyl)-piperazine-1-
	carboxamide
338	N-(3-Cyanophenyl)-4-[6-[1-[4-cyano-3-	6	593
	(trifluoromethyl)-phenyl]-2,5-dihydro-4-
	methyl-2,5-dioxo-1H-pyrrol-3-yl]-hexyl]pipera-
	zine-1-carboxamide
339	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	628
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(3,5-dimethoxy-phenyl)pipera-
	zine-1-carboxamide
340	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	614
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[3-(methylsulfanyl)phenyl]pipera-
	zine-1-carboxamide
341	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	660
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(4-phenoxy-phenyl)piperazine-1-
	carboxamide
342	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	614
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[4-(methylsulfanyl)phenyl]pipera-
	zine-1-carboxamide
343	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	610
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[4-(1-methylethyl)phenyl]pipera-
	zine-1-carboxamide
344	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	596
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(2-phenylethyl)-piperazine-1-
	carboxamide
345	N-([1,1′-Biphenyl]-2-yl)-4-[6-[1-[4-cyano-3-	6	644
	(trifluoromethyl)-phenyl]-2,5-dihydro-4-
	methyl-2,5-dioxo-1H-pyrrol-3-yl]-hexyl]pipera-
	zine-1-carboxamide
346	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	674
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[4-(phenyl-methoxy)phenyl]pipera-
	zine-1-carboxamide
347	N-(2-Cyanophenyl)-4-[6-[1-[4-cyano-3-	6	593
	(trifluoromethyl)-phenyl]-2,5-dihydro-4-
	methyl-2,5-dioxo-1H-pyrrol-3-yl]-hexyl]pipera-
	zine-1-carboxamide
348	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	602
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[2-(thien-2-yl)-ethyl]piperazine-1-
	carboxamide
349	(1R-trans)-4-[6-[1-[4-Cyano-3-(trifluoro-	6	608
	methyl)-phenyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-3-yl]hexyl]-N-(2-phenylcyclo-
	propyl)-piperazine-1-carboxamide
350	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	604
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(2,6-difluorophenyl)piperazine-1-
	carboxamide
351	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	636
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(2,6-dichlorophenyl)piperazine-1-
	carboxamide
352	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	628
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(2,4-dimethoxy-phenyl)pipera-
	zine-1-carboxamide
353	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	628
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(2,5-dimethoxy-phenyl)pipera-
	zine-1-carboxamide
354	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	596
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(2,6-dimethyl-phenyl)piperazine-1-
	carboxamide
355	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	637
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(trichloroacetyl)-piperazine-1-
	carboxamide
356	(S)-4-[6-[1-[4-Cyano-3-(trifluoromethyl)	6	596
	phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-3-yl]hexyl]-N-(1-phenylethyl)pipera-
	zine-1-carboxamide
357	(R)-4-[6-[1-[4-Cyano-3-(trifluoromethyl)	6	646
	phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-3-yl]hexyl]-N-[1-(naphthalen-1-yl)
	ethyl]piperazine-1-carboxamide
358	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	671
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(2,4,6-trichlorophenyl)pipera-
	zine-1-carboxamide
359	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	610
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[2-(1-methylethyl)phenyl]pipera-
	zine-1-carboxamide
360	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	636
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(3,5-dichlorophenyl)piperazine-1-
	carboxamide
361	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	610
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(2,4,6-trimethyl-phenyl)pipera-
	zine-1-carboxamide
362	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	668
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[4-[(trifluoromethyl)sulfanyl]
	phenyl]piperazine-1-carboxamide
363	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	651
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[(2,4-dichlorophenyl)
	methyl]piperazine-1-carboxamide
364	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	614
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[2-(methylsulfanyl)phenyl]pipera-
	zine-1-carboxamide
365	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	637
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(2,6-dichloropyridin-4-yl)pipera-
	zine-1-carboxamide
366	(R)-4-[6-[1-[4-Cyano-3-(trifluoromethyl)	6	596
	phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-3-yl]hexy]-N-(1-phenylethyl)pipera-
	zine-1-carboxamide
367	(S)-4-[6-[1-[4-Cyano-3-(trifluoromethyl)	6	646
	phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-3-yl]hexyl]-N-[1-(naplithalen-1-yl)thyl]
	piperazine-1-carboxamide
368	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	650
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[1-methyl-1-[3-(1-methylethenyl)
	phenyl]-ethyl]piperazine-1-carboxamide
369	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	652
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[2-(trifluoromethoxy)phenyl]
	piperazine-1-carboxamide
370	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	626
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(tricyclo[3.3.1.13.7]dec-1-
	yl)piperazine-1-carboxamide
371	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	611
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[4-(dimethylamino)phenyl]pipera-
	zine-1-carboxamide
372	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	668
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[3-[(trifluoromethyl)sulfanyl]
	phenyl]piperazine-1-carboxamide
373	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	596
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[(2-methylphenyl)methyl]pipera-
	zine-1-carboxamide
374	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	596
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[(3-methylphenyl)methyl]pipera-
	zine-1-carboxamide
375	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	596
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[(4-methylphenyl)methyl]pipera-
	zine-1-carboxamide
376	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	612
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-[(4-methoxyphenyl)methyl]pipera-
	zine-1-carboxamide
377	4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	604
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]-N-(1,1,3,3-tetramethylbutyl)pipera-
	zine-1-carboxamide

[0310]

TABLE 11
Compounds of General Formula I According to the Invention, in which
V = Trifluoromethylbenzonitrile, W = Maleimide, n = 7
		Synthesis
		Analogous
Ex-		to	ESI-
ample	Name	Example	MS
378	4-[3-[7-(4-Acetylpiperazin-1-yl)heptyl]-2,5-	9 (4)	504
	dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-
	yl]-2-(trifluoromethyl)-benzonitrile
379	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[7-	9 (4)	518
	(4-(1-oxopropyl)-piperazin-1-yl)heptyl]-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
380	4-[3-[7-[4-(Cyclopropylcarbonyl)piperazin-1-	9 (4)	530
	yl]heptyl]-2,5-dihydro-4-methyl-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzo-
	nitrile
381	4-[2,5-Dihydro-3-[7-[4-	9 (4)	534
	(methoxyacetyl)piperazin-1-yl]-heptyl]-
	4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-
	2-(trifluoromethyl)benzonitrile
382	4-[2,5-Dihydro-3-[7-[4-(3-methoxy-1-	9 (4)	548
	oxopropyl)piperazin-1-yl]heptyl]-4-methyl-
	2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
383	4-[2,5-Dihydro-3-[7-[4-[(2-methoxyethoxy)-	9 (4)	578
	acetyl]piperazin-1-yl]heptyl]-4-methyl-
	2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
384	4-[2,5-Dihydro-3-[7-[4-[[2-(2-methoxy-	9 (4)	622
	ethoxy)-ethoxy]-acetyl]piperazin-1-
	yl]heptyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-
	yl]-2-(trifluoromethyl)-benzonitrile
385	4-[2,5-Dihydro-3-[7-[4-(2-methoxybenzoyl)-	9 (4)	596
	piperazin-1-yl]-heptyl]-4-methyl-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzo-
	nitrile
386	4-[2,5-Dihydro-3-methyl-4-[7-[4-	9	540
	(methylsulfonyl)piperazin-1-yl]heptyl]-
	2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
387	4-[3-[7-[4-(Ethylsulfonyl)piperazin-	9	554
	1-yl]heptyl]-2,5-dihydro-4-methyl-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
388	4-[3-[7-[4-(Cyclopropylsulfonyl)piperazin-1-	9	566
	yl]heptyl]-2,5-dihydro-4-methyl-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzo-
	nitrile
389	4-[2,5-Dihydro-3-[7-[4-(2-methoxyethyl)-	9	584
	sulfonyl]piperazin-1-yl]heptyl]-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)-
	benzonitrile
390	4-[2,5-Dihydro-3-[7-[4-[[2-(2-	9	628
	methoxyethoxy)-ethyl]-sulfonyl]piperazin-
	1-yl]heptyl]-4-methyl-
	2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)-benzonitrile
391	4-[2,5-Dihydro-3-[7-[4-[[2-[2-(2-	9	672
	methoxyethoxy)ethoxy]-ethyl]sul-
	fonyl]piperazin-1-yl]heptyl]-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)benzonitrile
392	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[7-[4-	9	602
	(phenylsulfonyl)piperazin-1-yl]heptyl]-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile
393	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[7-[4-	9	616
	[(phenylmethyl)-sulfonyl]piperazin-1-
	yl]heptyl]-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
394	4-[2,5-Dihydro-3-methyl-4-[7-[4-[(1-methyl-	9	606
	1H-imidazol-4-yl)sulfonyl]piperazin-1-
	yl]heptyl]-2,5-dioxo-1H-pyrrol-1-yl]-
	2-(trifluoromethyl)-benzonitrile
395	4-[7-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	9 (6)	547
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]heptyl]-N-(1-methylethyl)-piperazine-1-
	carboxamide
396	4-[7-[1-[4-Cyano-3-	9 (12)	549
	(trifluoromethyl)phenyl]-2,5-
	dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]heptyl]-N-ethylpiperazine-1-
	carbothioamide
397	Methyl 4-[7-[1-[4-cyano-3-(trifluoromethyl)-	9 (13)	520
	phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-3-yl]heptyl]-piperazine-1-carboxylate
398	S-Methyl 4-[7-[1-[4-cyano-3-(trifluoro-	9 (13)	536
	methyl)-phenyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-3-yl]-heptyl]piperazine-1-
	carbothioate
399	4-[7-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	9	569
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]heptyl]-N,N-dimethylpiperazine-1-
	sulfonamide

[0311]

TABLE 12
Compounds of General Formula I According to the Invention, in which
V = Trifluoromethylbenzonitrile, W = Maleimide, n = 8
		Synthesis
		Analogous
Ex-		to	ESI-
ample	Name	Example	MS
400	4-[3-[8-(4-Acetylpiperazin-1-yl)octyl]-2,5-	9 (4)	518
	4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
401	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[8-(4-	9 (4)	532
	(1-oxopropyl)-piperazin-1-yl)octyl]-1H-
	pyrrol-1-yl]-2-(trifluoromethyl)-benzonitrile
402	4-[3-[8-[4-(Cyclopropylcarbonyl)piperazin-1-	9 (4)	544
	yl]octyl]-2,5-dihydro-4-methyl-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzo-
	nitrile
403	4-[2,5-Dihydro-3-[8-[4-(methoxy-	9 (4)	548
	acetyl)piperazin-1-yl]-octyl]-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)benzonitrile
404	4-[2,5-Dihydro-3-[8-[4-(3-methoxy-1-	9 (4)	562
	oxopropyl)-piperazin-1-yl]octyl]-4-methyl-
	2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)benzonitrile
405	4-[2,5-Dihydro-3-[8-[4-[(2-methoxyethoxy)-	9 (4)	592
	acetyl]piperazin-1-yl]octyl]-4-methyl-
	2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
406	4-[2,5-Dihydro-3-[8-[4-[[2-(2-	9 (4)	636
	methoxyethoxy)-ethoxy]-acetyl]piperazin-1-
	yl]octyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-
	yl]-2-(trifluoromethyl)-benzonitrile
407	4-[2,5-Dihydro-3-[8-[4-(2-methoxybenzoyl)-	9 (4)	610
	piperazin-1-yl]-octyl]-4-methyl-
	2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)-benzonitrile
408	4-[2,5-Dihydro-3-methyl-4-[8-[4-	9	554
	(methylsulfonyl)-piperazin-1-yl]octyl]-
	2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)-benzonitrile
409	4-[3-[8-[4-(Ethylsulfonyl)piperazin-	9	568
	1-yl]octyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-
	(trifluromethyl)benzonitrile
410	4-[3-[8-[4-(Cyclopropylsulfonyl)piperazin-1-	9	580
	yl]octyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
411	4-[2,5-Dihydro-3-[8-[4-(2-methoxyethyl)-	9	598
	sulfonyl]piperazin-1-yl]octyl]-4-methyl-
	2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)benzonitrile
412	4-[2,5-Dihydro-3-[8-[4-[[2-(2-	9	642
	methoxyethoxy)-ethyl]sulfonyl]piperazin-1-
	yl]octyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-
	yl]-2-(trifluoromethyl)-benzonitrile
413	4-[2,5-Dihydro-3-[8-[4-[[2-[2-(2-	9	686
	methoxyethoxy)-ethoxy]-ethyl]
	sulfonyl]piperazin-1-yl]octyl]-4-
	methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)benzonitrile
414	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[8-[4-	9	616
	(phenylsulfonyl)piperazin-1-yl]octyl]-
	1H-pyrrol-1-yl]-2-(trifluoromethyl)benzo-
	nitrile
415	4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[8-[4-	9	630
	[(phenylmethyl)-sulfonyl]piperazin-1-
	yl]octyl]-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)benzonitrile
416	4-[2,5-Dihydro-3-methyl-4-[8-[4-[(1-	9	620
	methyl-1H-imidazol-4-yl)sulfonyl]piperazin-
	1-yl]octyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)-benzonitrile
417	4-[8-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	6	561
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]octyl]-N-(1-methylethyl)-piperazine-1-
	carboxamide
418	4-[8-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	9 (12)	563
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]octyl]-N-ethylpiperazine-1-
	carbothioamide
419	Methyl 4-[8-[1-[4-cyano-3-(trifluoromethyl)-	9 (13)	534
	phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-3-yl]octyl]piperazine-1-carboxylate
420	S-Methyl 4-[8-[1-[4-cyano-3-(trifluoro-	9 (13)	550
	methyl)-phenyl]-2,5-dihydro-4-methyl-
	2,5-dioxo-1H-pyrrol-3-yl]octyl]piperazine-
	1-carbothioate
421	4-[8-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-	9	583
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]octyl]-N,N-dimethylpiperazine-1-
	sulfonamide

[0312]

TABLE 13
Compounds of General Formula I According to the Invention, in which
V = Trifluoromethylphenylacetamide, W = Maleimide, n = 6
		Synthesis
		Analogous
Ex-		to	ESI-
ample	Name	Example	MS
422	N-[4-[2,5-Dihydro-3-[6-[4-(2-	4	615
	methoxybenzoyl)-piperazin-1-yl]hexyl]-4-
	methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-
	(trifluoromethyl)phenyl]acetamide
423	N-[4-[3-[6-[4-(Cyclobutylcarbonyl)piperazin-	4	563
	1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-
	1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)phenyl]acetamide
424	N-[4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-	4	591
	[6-[4-[(thien-2-yl)-carbonyl]piperazin-1-
	yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)phenyl]acetamide
425	N-[4-[3-[6-[4-[4-(Dimethyl-	4	628
	amino)benzoyl]-piperazin-1-yl]-hexyl]-
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-
	yl]-2-(trifluoromethyl)-phenyl]acetamide
426	N-[4-[3-[6-(4-Acetylpiperazin-1-	4	523
	yl)hexyl]-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)phenyl]acetamide
427	N-[4-[2,5-Dihydro-3-methyl-4-[6-[4-	5	559
	(methylsulfonyl)-piperazin-1-yl]hexyl]-
	2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoro-
	methyl)phenyl]-acetamide
428	N-[4-[3-[6-[4-[(2,1,3-Benzothiadiazol-4-	5	679
	yl)sulfonyl]-piperazin-1-yl]hexyl]-
	2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-
	yl]-2-(trifluoromethyl)phenyl]acetamide
429	4-[6-[1-[4-(Acetylamino)-3-(trifluoro-	6	601
	methyl)-phenyl]-2,5-dihydro-4-methyl-
	2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-
	(pyridin-4-yl)piperazine-1-carboxamide

[0313]

TABLE 14
Compounds of General Formula I According to the Invention, in which
V = Nitrotrifluoromethylbenzene, W = Maleimide, n = 6
		Synthesis
		Analogous
Ex-		to	ESI-
ample	Name	Example	MS
430	3-[6-[4-(Cyclobutylcarbonyl)piperazin-1-	4	551
	yl]hexyl]-4-methyl-1-[4-nitro-3-(trifluoro-
	methyl)phenyl]-1H-pyrrole-2,5-dione
431	3-[6-[4-[4-(Dimethylamino)benzoyl]	4	616
	piperazin-1-yl]hexyl]-4-methyl-1-[4-
	nitro-3-(trifluoromethyl)-phenyl]-
	1H-pyrrole-2,5-dione
432	3-[6-(4-Acetylpiperazin-1-yl)hexyl]-	4	511
	4-methyl-1-[4-nitro-3-(trifluoro-
	methyl)phenyl]-1H-pyrrole-2,5-dione
433	3-Methyl-4-[6-[4-(methyl-	5	547
	sufonyl)piperazin-1-yl]hexyl]-1-[4-nitro-
	3-(trifluoromethyl)phenyl]-1H-pyrrole-
	2,5-dione
434	3-[6-[4-[(2,1,3-Benzothiadiazol-4-	5	667
	yl)sulfonyl]-piperazin-1-yl]hexyl]-4-methyl-
	1-[4-nitro-3-(trifluoromethyl)phenyl]-1H-
	pyrrole-2,5-dione

[0314]

TABLE 15
Compounds of General Formula I According to the Invention, in which
V = Bistrifluoromethylbenzene, W = Maleimide, n = 6
		Synthesis
		Analogous
Ex-		to	ESI-
ample	Name	Example	MS
435	1-[3,4-Bis(trifluoromethyl)phenyl]-3-	4	626
	[6-[4-(2-methoxy-benzoyl)piperazin-1-
	yl]hexyl]-4-methyl-1H-pyrrole-2,5-dione
436	3-[6-(4-Acetylpiperazin-1-yl)hexyl]-1-[3,4-	4	534
	bis(trifluoromethyl)phenyl]-4-methyl-1H-
	pyrrole-2,5-dione
437	1-[3,4-Bis(trifluoromethyl)phenyl]-3-[6-[4-	4	574
	(cyclobutyl-carbonyl)piperazin-1-
	yl]hexyl]-4-methyl-1H-pyrrole-2,5-dione
438	1-[3,4-Bis(trifluoromethyl)phenyl]-3-	4	602
	methyl-4-[6-[4-[(thien-2-
	yl)carbonyl]piperazin-1-yl]hexyl]-1H-
	pyrrole-2,5-dione
439	1-[3,4-Bis(trifluoromethyl)phenyl]-3-[6-[4-	4	639
	[4-(dimethylamino)benzoyl]piperazin-1-
	yl]hexyl]-4-methyl-1H-pyrrole-2,5-dione
440	1-[3,4-Bis(trifluoromethyl)phenyl]-3-methyl-	5	570
	4-[6-[4-(methyl-sulfonyl)piperazin-1-
	yl]hexyl]-1H-pyrrole-2,5-dione
441	3-[6-[4-[(2,1,3-Benzothiadiazol-4-	5	690
	yl)sulfonyl]-piperazin-1-yl]hexyl]-1-
	[3,4-bis(trifluoromethyl)-phenyl]-
	4-methyl-1H-pyrrole-2,5-dione

[0315]

TABLE 16
Compounds of General Formula I According to the Invention, in which
V = Fluorotrifluoromethylbenzene, W = Maleimide, n = 6
		Synthesis
		Analogous
Ex-		to	ESI-
ample	Name	Example	MS
442	1-[3-Fluoro-4-(trifluoromethyl)phenyl]-3-[6-	4	576
	[4-(2-methoxy-benzoyl)piperazin-1-
	yl]hexyl]-4-methyl-1H-pyrrole-2,5-dione
443	3-[6-[4-(Cyclobutylcarbonyl)piperazin-1-	4	524
	yl]hexyl]-1-[3-fluoro-4-(trifluoro-
	methyl)phenyl]-4-methyl-1H-pyrrole-2,5-
	dione
444	1-[3-Fluoro-4-(trifluoromethyl)phenyl]-	4	552
	3-methyl-4-[6-[4-(thien-2-
	yl)carbonyl]piperazin-1-yl]hexyl]-
	1H-pyrrole-2,5-dione
445	3-[6-[4-[4-(Dimethyl-	4	589
	amino)benzoyl]piperazin-1-yl]hexyl]-
	1-[3-fluoro-4-(trifluoromethyl)phenyl]-4-
	methyl-1H-pyrrole-2,5-dione
446	3-[6-[4-Acetylpiperazin-1-yl)hexyl]-1	4	484
	-[3-fluoro-4-(trifluoromethyl)phenyl]-4-
	methyl-1H-pyrrole-2,5-dione
447	1-[3-Fluoro-4-(trifluoromethyl)phenyl]-3-	5	520
	methyl-4-[6-[4-(methylsulfonyl)piperazin-
	1-yl]hexyl]-1H-pyrrole-2,5-dione
448	3-[6-[4-[(2,1,3-Benzothiadiazol-	5	640
	4-yl)sulfonyl]-piperazin-1-yl]hexyl]-
	1-[3-fluoro-4-(trifluoromethyl)phenyl]-4-
	methyl-1H-pyrrole-2,5-dione

[0316]

TABLE 17
Compounds of General Formula I According to the Invention, in which
V = Isobenzofuranone, W = Maleimide, n = 4
		Synthesis
		Analogous
Ex-		to	ESI-
ample	Name	Example	MS
449	3-[4-(4-Acetylpiperazin-1-yl)butyl]-	4	425
	1-(1,3-dihydro-1-oxo-isobenzofuran-5-yl)-4-
	methyl-1H-pyrrole-2,5-dione
450	1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-	4	440
	methyl-4-[4-[4-(1-oxopropyl)piperazin-1-
	yl]butyl]-1H-pyrrole-2,5-dione
451	1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	4	500
	3-[4-[4-[(2-methoxyethoxy)acetyl]-
	piperazin-1-yl]butyl]-4-methyl-1H-
	pyrrole-2,5-dione
452	1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	4	544
	3-[4-[4-[[2-(2-methoxyethoxy)ethoxy]acetyl]
	piperazin-1-yl]butyl]-4-methyl-1H-pyrrole-
	2,5-dione
453	1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-	5	462
	methyl-4-[4-[4-(methylsulfonyl)piperazin-1-
	yl]butyl]-1H-pyrrole-2,5-dione
454	4-[4-[1-(1,3-Dihydro-1-oxoisobenzofuran-5-	12	471
	yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-3-yl]butyl]-N-ethyl-piperazine-1-
	carbothioamide
455	4-[4-[1-(1,3-Dihydro-1-oxoisobenzofuran-	12	485
	5-yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-3-yl]butyl]-N-propyl-piperazine-1-
	carbothioamide
456	4-[4-[1-(1,3-Dihydro-1-oxoisobenzofuran-5-	12	483
	yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-3-yl]butyl]-N-(prop-2-enyl)piperazine-
	1-carbothioamide

[0317]

TABLE 18
Compounds of General Formula I According to the Invention, in which
V = Isobenzofuranone, W = Maleimide, n = 5
		Synthesis
		Analogous
Ex-		to	ESI-
ample	Name	Example	MS
457	3-[5-(4-Acetylpiperazin-1-yl)pentyl]-1-(1,3-	4	439
	dihydro-1-oxo-isobenzofuran-5-yl)-4-methyl-
	1H-pyrrole-2,5-dione
458	1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-	4	454
	methyl-4-[5-[4-(1-oxopropyl)piperazin-1-
	yl]pentyl]-1H-pyrrole-2,5-dione
459	1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	4	514
	3-[5-[4-[(2-methoxyethoxy)acetyl]piperazin-
	1-yl]pentyl]-4-methyl-1H-pyrrole-2,5-dione
460	1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-	4	558
	[5-[4-[[2-(2-methoxy-
	ethoxy)ethoxy]acetyl]piperazin-1-
	yl]pentyl]-4-methyl-1H-pyrrole-2,5-dione
461	1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-	5	476
	methyl-4-[5-[4-(methylsulfonyl)piperazin-1-
	yl]pentyl]-1H-pyrrole-2,5-dione
462	3-[5-[4-(Cyclopropylsulfonyl)piperazin-1-	5	502
	yl]pentyl]-1-(1,3-dihydro-1-oxoiso-
	benzofuran-5-yl)-4-methyl-1H-pyrrole-2,5-
	dione
463	1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-	5	608
	[5-[4-[[2-[2-(2-methoxy-
	ethoxy)ethoxy]ethyl]-
	sulfonyl]piperazin-1-yl]-pentyl]-4-methyl-
	1H-pyrrole-2,5-dione
464	4-[5-[1-(1,3-Dihydro-1-oxoisobenzo-	12	471
	furan-5-yl)-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-3-yl]pentyl]-N-ethyl-
	piperazine-1-carbothioamide
465	4-[5-[1-(1,3-Dihydro-1-oxoisobenzo-	12	485
	furan-5-yl)-2,5-dihydro-4-methyl-2,5-dioxo-
	1H-pyrrol-3-yl]pentyl]-N-propyl-
	piperazine-1-carbothioamide
466	4-[5-[1-(1,3-Dihydro-1-oxoisobenzo-	12	483
	furan-5-yl)-2,5-dihydro-4-methyl-2,5-
	dioxo-1H-pyrrol-3-yl]pentyl]-N-
	(prop-2-enyl)piperazine-1-carbothioamide

[0318]

TABLE 19
Compounds of General Formula I According to the Invention, in which
V = Isobenzofuranone, W = Maleimide, n = 6
		Synthesis
		Analogous
Ex-		to	ESI-
ample	Name	Example	MS
467	1-(1,3-Dihydro-1-oxoisobenzofuran-5-	4	546
	yl)-3-[6-[4-(2-methoxybenzoyl)piperazin-
	1-yl]hexyl]-4-methyl-1H-pyrrole-2,5-dione
468	3-[6-[4-(Cyclobutylcarbonyl)piperazin-	4	494
	1-yl]hexyl]-1-(1,3-dihydro-1-oxoisobenzo-
	furan-5-yl)-4-methyl-1H-pyrrole-2,5-dione
469	1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-	4	522
	methyl-4-[6-[4-[(thien-2-
	yl)carbonyl]piperazin-1-yl]hexyl]-
	1H-pyrrole-2,5-dione
470	1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-	4	559
	[6-[4-[4-(dimethyl-
	amino)benzoyl]piperazin-1-yl]hexyl]-
	4-methyl-1H-pyrrole-2,5-dione
471	3-[6-(4-Acetylpiperazin-1-yl)hexyl]-1-(1,3-	4	454
	dihydro-1-oxoisobenzofuran-5-yl)-4-methyl-
	1H-pyrrole-2,5-dione
472	4-[4-[1-(1,3-Dihydro-1-oxoisobenzofuran-5-	5	519
	yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-3-yl]hexyl]-N,N-dimethylpiperazine-
	1-sulfonamide
473	1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-	5	490
	methyl-4-[6-[4-(methylsulfonyl)piperazin-1-
	yl]hexyl]-1H-pyrrole-2,5-dione
474	3-[6-[4-[(2,1,3-Benzothiadiazol-4-	5	610
	yl)sulfonyl]-piperazin-1-yl]hexyl]-1-(1,3-
	dihydro-1-oxoisobenzofuran-5-yl)-4-methyl-
	1H-pyrrole-2,5-dione
475	1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-	5	504
	[6-[4-(ethyl-sulfonyl)piperazin-1-yl]hexyl]-
	4-methyl-1H-pyrrole-2,5-dione
476	4-[6-[1-(1,3-Dihydro-1-oxoisobenzofuran-5-	12	499
	yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-3-yl]hexyl]-N-ethyl-piperazine-1-
	carbothioamide
477	4-[6-[1-(1,3-Dihydro-1-oxoisobenzofuran-5-	12	513
	yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-3-yl]hexyl]-N-propyl-piperazine-
	1-carbothioamide
478	4-[6-[1-(1,3-Dihydro-1-oxoisobenzofuran-	12	511
	5-yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-3-yl]hexyl]-N-(prop-2-
	enyl)piperazine-1-carbothioamide
479	4-[6-[1-(1,3-Dihydro-1-oxoisobenzofuran-5-	12	561
	yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-3-yl]hexyl]-N-(phenyl-
	methyl)piperazine-1-carbothioamide
480	4-[6-[1-(1,3-Dihydro-1-oxoisobenzofuran-5-	12	575
	yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-3-yl]hexyl]-N-[(4-methyl-
	phenyl)methyl]piperazine-1-carbothioamide
481	N-[(4-Chlorophenyl)methyl]-4-[6-[1-	12	595
	(1,3-dihydro-1-oxo-isobenzofuran-5-yl)-2,5-
	dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-
	yl]hexyl]piperazine-1-carbothioamide
482	4-[6-[1-(1,3-Dihydro-1-oxoisobenzofuran-5-	12	547
	yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-3-yl]hexyl]-N-phenylpiperazine-1-
	carbothioamide
483	4-[6-[1-(1,3-Dihydro-1-oxoisobenzofuran-	12	575
	5-yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-
	pyrrol-3-yl]hexyl]-N-(2,6-dimethyl-
	phenyl)piperazine-1-carbothioamide

[0319]

TABLE 20
Compounds of General Formula I According to the Invention, in which
V = Methylbenzoxazinone, W = Maleimide, n = 6
		Synthesis
		Analogous
Ex-		to	ESI-
ample	Name	Example	MS
484	3-[6-[4-(2-Methoxybenzoyl)piperazin-1-	4	573
	yl]hexyl]-4-methyl-1-(4-methyl-1-oxo-1H-
	2,3-benzoxazin-6-yl)-1H-pyrrole-2,5-dione
485	3-[6-[4-(Cyclobutylcarbonyl)piperazin-1-
	yl]hexyl]-4-methyl-1-(4-methyl-1-oxo-1H-	4	521
	2,3-benzoxazin-6-yl)-1H-pyrrole-2,5-dione
486	3-Methyl-1-(4-methyl-1-oxo-1H-2,3-	4	549
	benzoxazin-6-yl)-4-[6-[4-[(thien-2-
	yl)carbonyl]piperazin-1-yl]hexyl]-1H-
	pyrrole-2,5-dione
487	3-[6-[4-[4-(Dimethyl-	4	586
	amino)benzoyl]piperazin-1-yl]hexyl]-4-
	methyl-1-(4-methyl-1-oxo-1H-2,3-
	benzoxazin-6-yl)-1H-pyrrole-2,5-dione
488	3-[6-(4-Acetylpiperazin-1-yl)hexyl]-4-	4	481
	methyl-1-(4-methyl-1-oxo-1H-2,3-
	benzoxazin-6-yl)-1H-pyrrole-2,5-dione
489	3-Methyl-1-(4-methyl-1-oxo-1H-2,3-	5	517
	benzoxazin-6-yl)-4-[6-[4-(methyl-
	sulfonyl)piperazin-1-yl]hexyl]-1H-pyrrole-
	2,5-dione

[0320]

TABLE 21
Compounds of General Formula I According to the Invention, in which
V = Indanone, W = Maleimide, n = 6
		Synthesis
		Anal-
Ex-		ogous
am-		to	ESI-
ple	Name	Example	MS
490	1-(2,3-Dihydro-1-oxo-1H-inden-5-yl)-3-[6-[4-	4	544
	(2-methoxy-benzoyl)piperazin-1-yl]hexyl]-4-
	methyl-1H-pyrrole-2,5-dione
491	3-[6-[4-(Cyclobutylcarbonyl)piperazin-1-	4	492
	yl]hexyl]-1-(2,3-dihydro-1-oxo-1H-inden-5-yl)-
	4-methyl-1H-pyrrole-2,5-dione
492	1-(2,3-Dihydro-1-oxo-1H-inden-5-yl)-3-	4	520
	methyl-4-[6-[4-[(thien-2-yl)carbonyl]piperazin-
	1-yl]hexyl]-1H-pyrrole-2,5-dione
493	1-(2,3-Dihydro-1-oxo-1H-inden-5-yl)-3-[6-[4-	4	557
	[4-(dimethylamino)benzoyl]piperazin-1-
	yl]hexyl]-4-methyl-1H-pyrrole-2,5-dione
494	3-[6-(4-Acetylpiperazin-1-yl)hexyl]-1-(2,3-	4	452
	dihydro-1-oxo-1H-inden-5-yl)-4-methyl-1H-
	pyrrole-2,5-dione
495	1-(2,3-Dihydro-1-oxo-1H-inden-5-yl)-3-	5	488
	methyl-4-[6-[4-(methylsulfonyl)piperazin-1-
	yl]hexyl]-1H-pyrrole-2,5-dione
496	3-[6-[4-[(2,1,3-Benzothiadiazol-4-	5	608
	yl)sulfonyl]piperazin-1-yl]hexyl]-1-(2,3-
	dihydro-1-oxo-1H-inden-5-yl)-4-methyl-1H-
	pyrrole-2,5-dione

[0321]

TABLE 22
Compounds of General Formula I According to the Invention, in which
V = Trifluoromethylbenzonitrile, W = Thiohydantoin, n = 2
		Synthesis
		Anal-
Ex-		ogous
am-		to	ESI-
ple	Name	Example	MS
497	4-[3-[2-(4-Acetylpiperazin-1-yl)ethyl]-4,4-	15 (4)	468
	dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
498	4-[4,4-Dimethyl-5-oxo-3-[2-[4-(1-oxopropyl)-	15 (4)	482
	piperazin-1-yl]-ethyl]-2-thioxoimidazolidin-1-
	yl]-2-(trifluoromethyl)-benzonitrile
499	4-[4,4-Dimethyl-3-[2-[4-(2-methyl-1-	15 (4)	496
	oxopropyl)-piperazin-1-yl]ethyl]-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
500	4-[4,4-Dimethyl-5-oxo-3-[2-[4-(1-oxobutyl)-	15 (4)	496
	piperazin-1-yl]-ethyl]-2-thioxoimidazolidin-1-
	yl]-2-(trifluoromethyl)-benzonitrile
501	4-[3-[2-[4-(Cyclopropylcarbonyl)piperazin-1-	15 (4)	494
	yl]ethyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
502	4-[3-[2-[4-(Cyclobutylcarbonyl)piperazin-1-	15 (4)	508
	yl]ethyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-
	1-yl]-2-(trifluoromethyl)benzonitrile
503	4-[4,4-Dimethyl-5-oxo-3-[2-[4-[(thien-2-	15 (4)	550
	yl)acetyl]-piperazin-1-yl]ethyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
504	4-[4,4-Dimethyl-5-oxo-3-[2-[4-[(thien-2-	15 (4)	536
	yl)carbonyl]-piperazin-1-yl]ethyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
505	4-[4,4-Dimethyl-5-oxo-3-[2-[4-[(pyridin-4-	15 (4)	531
	yl)carbonyl]-piperazin-1-yl]ethyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
506	4-[4,4-Dimethyl-3-[2-[4-(methylsulfonyl)piper-	15 (5)	504
	azin-1-yl]-ethyl]-5-oxo-2-thioxoimidazolidin-1-
	yl]-2-(trifluoromethyl)-benzonitrile
507	4-[3-[2-[4-(Ethylsulfonyl)piperazin-1-yl]ethyl]-	15 (5)	518
	4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-
	2-(trifluoromethyl)-benzonitrile
508	4-[4,4-Dimethyl-5-oxo-3-[2-[4-(propyl-	15 (5)	532
	sulfonyl)-piperazin-1-yl]ethyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
509	4-[4,4-Dimethyl-5-oxo-3-[2-[4-(phenyl-	15 (5)	566
	sulfonyl)-piperazin-1-yl]ethyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
510	4-[3-[2-[4-[(4-Cyanophenyl)sulfonyl]piperazin-	15 (5)	591
	1-yl]ethyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)
	benzonitrile
511	4-[2-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-	15 (12)	513
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]ethyl]-N-ethylpiperazine-1-carbothioamide
512	4-[2-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-	15 (12)	527
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]ethyl]-N-propylpiperazine-1-carbothioamide
513	4-[2-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-	15 (12)	525
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]ethyl]-N-(prop-2-enyl)-piperazine-1-
	carbothioamide
514	S-Methyl 4-[2-[3-[4-cyano-3-(trifluoromethyl)-	15 (13)	500
	phenyl]-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]ethyl]piperazine-1-
	carbothioate
515	S-Ethyl 4-[2-[3-[4-cyano-3-(trifluoromethyl)-	15 (13)	514
	phenyl]-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]ethyl]piperazine-1-
	carbothioate

[0322]

TABLE 23
Compounds of General Formula I According to the Invention, in which
V = Trifluoromethylbenzonitrile, W = Thiohydantoin, n = 3
		Synthesis
		Anal-
Ex-		ogous
am-		to	ESI-
ple	Name	Example	MS
516	4-[3-[3-[4-(2-Methoxybenzoyl)piperazin-1-	15 (4)	574
	yl]propyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
517	4-[3-[3-(4-Acetylpiperazin-1-yl)propyl]-4,4-	15 (4)	482
	dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
518	4-[4,4-Dimethyl-5-oxo-3-[3-[4-(1-oxopropyl)-	15 (4)	496
	piperazin-1-yl]-propyl]-2-thioxoimidazolidin-1-
	yl]-2-(trifluoromethyl)-benzonitrile
519	4-[4,4-Dimethyl-3-[3-[4-(2-methyl-1-	15 (4)	510
	oxopropyl)piperazin-1-yl]propyl]-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
520	4-[4,4-Dimethyl-5-oxo-3-[3-[4-(1-oxobutyl)-	15 (4)	510
	piperazin-1-yl]-propyl]-2-thioxoimidazolidin-1-
	yl]-2-(trifluoromethyl)-benzonitrile
521	4-[3-[3-[4-(Cyclopropylcarbonyl)piperazin-1-	15 (4)	508
	yl]propyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
522	4-[3-[3-[4-(Cyclobutylcarbonyl)piperazin-1-	15 (4)	522
	yl]propyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
523	4-[4,4-Dimethyl-5-oxo-3-[3-[4-[(thien-2-	15 (4)	564
	yl)acetyl]piperazin-1-yl]propyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
524	4-[4,4-Dimethyl-5-oxo-3-[3-[4-[(thien-2-	15 (4)	550
	yl)carbonyl]-piperazin-1-yl]propyl]-2-
	thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
525	4-[4,4-Dimethyl-5-oxo-3-[3-[4-[(pyridin-4-	15 (4)	545
	yl)carbonyl]-piperazin-1-yl]propyl]-2-
	thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
526	4-[3-[3-[4-(3-Methoxy-1-oxopropyl)piperazin-	15 (4)	526
	1-yl]propyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
527	4-[3-[3-[4-[(2-Methoxyethoxy)acetyl]piperazin-	15 (4)	556
	1-yl]propyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
528	4-[3-[3-[4-[[2-(2-Methoxyethoxy)ethoxy]-	15 (4)	600
	acetyl]piperazin-1-yl]propyl]-4,4-dimethyl-5-
	oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
529	4-[4,4-Dimethyl-3-[3-[4-(methylsulfonyl)piper-	15 (5)	518
	azin-1-yl]-propyl]-5-oxo-2-thioxoimidazolidin-
	1-yl]-2-(trifluoromethyl)-benzonitrile
530	4-[3-[3-[4-(Ethylsulfonyl)piperazin-1-yl]pro-	15 (5)	532
	pyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-
	1-yl]-2-(trifluoromethyl)benzonitrile
531	4-[4,4-Dimethyl-5-oxo-3-[3-[4-(propyl-	15 (5)	546
	sulfonyl)-piperazin-1-yl]propyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
532	4-[3-[3-[4-[(2-Methoxyethyl)sulfonyl]piper-	15 (5)	562
	azin-1-yl]propyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
533	4-[4,4-Dimethyl-5-oxo-3-[3-[4-(phenyl-	15 (5)	580
	sulfonyl)-piperazin-1-yl]propyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
534	4-[3-[3-[4-[(4-Cyanophenyl)sulfonyl]piperazin-	15 (5)	605
	1-yl]propyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
535	4-[3-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-	15 (12)	527
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]propyl]-N-ethylpiperazine-1-carbothioamide
536	4-[3-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-	15 (12)	541
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]propyl]-N-propylpiperazine-1-
	carbothioamide
537	4-[3-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-	15 (12)	539
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]propyl]-N-(prop-2-enyl)-piperazine-1-
	carbothioamide
538	S-Methyl 4-[3-[3-[4-cyano-3-(trifluoromethyl)-	15 (13)	514
	phenyl]-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]propyl]piperazine-1-
	carbothioate
539	S-Ethyl 4-[3-[3-[4-cyano-3-(trifluoromethyl)-	15 (13)	528
	phenyl]-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]propyl]piperazine-1-
	carbothioate

[0323]

TABLE 24
Compounds of General Formula I According to the Invention, in which
V = Trifluoromethylbenzonitrile, W = Thiohydantoin, n = 4
		Synthesis
		Anal-
Ex-		ogous
am-		to	ESI-
ple	Name	Example	MS
540	4-[3-[4-[4-(2-Methoxybenzoyl)piperazin-1-	4	588
	yl]butyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)benzonitrile
541	4-[4-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-	4	479
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]butyl]piperazine-1-carbonitrile
542	4-[3-[4-(4-Acetylpiperazin-1-yl)butyl]-4,4-	4	496
	dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
543	rel-4-[3-[4-[(2R,5S)-4-Acetyl-2,5-	4	524
	dimethylpiperazin-1-yl]butyl]-4,4-dimethyl-5-
	oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
544	4-[3-[4-(4-Acetylhexahydro-1H-1,4-diazepin-1-	4	510
	yl)butyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)benzonitrile
545	4-[4,4-Dimethyl-5-oxo-3-[4-[4-(1-	4	510
	oxopropyl)piperazin-1-yl]butyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
546	4-[4,4-Dimethyl-3-[4-[4-(2-methyl-1-	4	524
	oxopropyl)piperazin-1-yl]butyl]-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
547	rel-4-[3-[4-[(2R,5S)-2,5-Dimethyl-4-(2-methyl-	4	552
	1-oxopropyl)piperazin-1-yl]butyl]-4,4-
	dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)-benzonitrile
548	4-[3-[4-[4-(2-Hydroxy-2-methyl-1-oxopropyl)-	4	540
	piperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluormethyl)-
	benzonitrile
549	4-[3-[4-[4-(2,2-Dimethyl-1-oxopropyl)piper-	4	538
	azin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)benzonitrile
550	rel-4-[3-[4-[(2R,5S)-4-(2,2-Dimethyl-1-	4	566
	oxopropyl)-2,5-dimethylpiperazin-1-yl]butyl]-
	4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-
	yl]-2-(trifluoromethyl)benzonitrile
551	4-[3-[4-[4-(2,2-Dimethyl-1-oxopropyl)hexa-	4	552
	hydro-1H-1,4-diazepin-1-yl]butyl]-4,4-
	dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)-benzonitrile
552	4-[4,4-Dimethyl-5-oxo-3-[4-[4-(1-	4	524
	oxobutyl)piperazin-1-yl]-butyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
553	4-[3-[4-[4-(Cyclopropylcarbonyl)piperazin-1-	4	522
	yl]butyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)
	benzonitrile
554	rel-4-[3-[4-[(2R,5S)-4-(Cyclopropylcarbonyl)-	4	550
	2,5-dimethylpiperazin-1-yl]butyl]-4,4-dimethyl-
	5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
555	4-[3-[4-[4-(Cyclobutylcarbonyl)piperazin-1-	4	536
	yl]butyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)benzonitrile
556	4-[4,4-Dimethyl-5-oxo-3-[4-[4-[(thien-2-	4	578
	yl)acetyl]piperazin-1-yl]butyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
557	4-[3-[4-[4-(Methoxyacetyl)piperazin-1-	4	526
	yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimida-
	zolidin-1-yl]-2-(trifluoromethyl)benzonitrile
558	4-[3-[4-[4-(3-Methoxy-1-oxopropyl)piperazin-	4	540
	1-yl]butyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)benzonitrile
559	4-[3-[4-[Hexahydro-4-(3-methoxy-1-oxo-	4	554
	propyl)-1H-1,4-diazepin-1-yl]butyl]-4,4-
	dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)-benzonitrile
560	4-[3-[4-[4-[(2-Methoxyethoxy)acetyl]piperazin-	4	570
	1-yl]butyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)benzonitrile
561	4-[3-[4-[4-[[2-(2-Methoxyethoxy)ethoxy]-	4	614
	acetyl]piperazin-1-yl]butyl]-4,4-dimethyl-5-
	oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
562	4-[4,4-Dimethyl-5-oxo-2-thioxo-3-[4-[4-	4	550
	(trifluoroacetyl)piperazin-1-yl]butyl]imida-
	zolidin-1-yl]-2-(trifluoromethyl)benzonitrile
563	4-[3-[4-[Hexahydro-4-(trifluoroacetyl)-1H-1,4-	4	564
	diazepin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
564	4-[3-[4-[4-[(1,3-Dimethyl-1H-pyrazol-5-	4	576
	yl)carbonyl]-piperazin-1-yl]butyl]-4,4-
	dimethyl-5-oxo-2-thioxo-imidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
565	4-[3-[4-[4-[(Furan-3-yl)carbonyl]piperazin-1-	4	548
	yl]butyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)benzonitrile
566	4-[3-[4-[4-[(2,5-Dimethylfuran-3-	4	576
	yl)carbonyl]piperazin-1-yl]butyl]-4,4-dimethyl-
	5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
567	4-[3-[4-[4-[(Isoxazol-5-yl)carbonyl]piperazin-	4	549
	1-yl]butyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)benzonitrile
568	4-[4,4-Dimethyl-3-[4-[4-[(5-methylisoxazol-3-	4	563
	yl)carbonyl]piperazin-1-yl]butyl]-5-oxo-2-
	thioxo-imidazolidin-1-yl]-2-(trifluoro-
	methyl)benzonitrile
569	4-[4,4-Dimethyl-5-oxo-3-[4-[4-[(thien-3-	4	564
	yl)carbonyl]-piperazin-1-yl]butyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
570	4-[4,4-Dimethyl-3-[4-[4-[(4-methyl-1,2,3-	4	580
	thiadiazol-4-yl)-carbonyl]piperazin-1-
	yl]butyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)-benzonitrile
571	4-[3-[4-[4-[(Furan-2-yl)carbonyl]piperazin-1-		548
	yl]butyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)benzonitrile
572	4-[3-[4-[4-[(Furan-2-yl)carbonyl]hexahydro-	4	562
	1H-1,4-diazepin-1-yl]butyl]-4,4-dimethyl-5-
	oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
573	4-[4,4-Dimethyl-5-oxo-3-[4-[4-[(thien-2-	4	564
	yl)carbonyl]-piperazin-1-yl]butyl]-2-
	thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
574	4-[3-[4-[Hexahydro-4-[(thien-2-yl)carbonyl]-	4	578
	1H-1,4-diazepin-1-yl]butyl]-4,4-dimethyl-5-
	oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
575	4-[4,4-Dimethyl-5-oxo-3-[4-[4-[(pyridin-4-	4	559
	yl)carbonyl]-piperazin-1-yl]butyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
576	4-[4,4-Dimethyl-3-[4-[4-(methylsulfonyl)piper-	5	532
	azin-1-yl]-butyl]-5-oxo-2-thioxoimidazolidin-1-
	yl]-2-(trifluoromethyl)-benzonitrile
577	rel-4-[4,4-Dimethyl-3-[4-[(2R,5S)-2,5-	5	560
	dimethyl-4-(methylsulfonyl)piperazin-1-
	yl]butyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)-benzonitrile
578	4-[3-[4-[Hexahydro-4-(methylsulfonyl)-1H-1,4-	5	546
	diazepin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
579	4-[3-[4-[4-(Ethylsulfonyl)piperazin-1-yl]butyl]-	5	546
	4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-
	yl]-2-(trifluoromethyl)-benzonitrile
580	4-[4,4-Dimethyl-5-oxo-3-[4-[4-(propyl-	5	560
	sulfonyl)-piperazin-1-yl]butyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
581	4-[3-[4-[4-[(2-Methoxyethyl)sulfonyl]piper-	5	576
	azin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)benzonitrile
582	4-[4,4-Dimethyl-5-oxo-3-[4-[4-(phenyl-	5	594
	sulfonyl)-piperazin-1-yl]butyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
583	4-[3-[4-[4-[(4-Cyanophenyl)sulfonyl]piper-	5	619
	azin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)benzonitrile
584	4-[4,4-Dimethyl-3-[4-[4-[(1-methyl-1H-	5	598
	imidazol-4-yl)-sulfonyl]piperazin-1-yl]butyl]-
	5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
585	4-[3-[4-[4-[(3,5-Dimethylisoxazol-4-	5	613
	yl)sulfonyl]-piperazin-1-yl]butyl]-4,4-dimethyl-
	5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)-benzonitrile
586	4-[4-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-	12	541
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]butyl]-N-ethylpiperazine-1-carbothioamide
587	4-[4-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-	12	555
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]butyl]-N-propylpiperazine-1-carbothioamide
588	4-[4-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-	12	553
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]butyl]-N-(prop-2-enyl)-piperazine-1-
	carbothioamide
589	S-Methyl 4-[4-[3-[4-cyano-3-(trifluoromethyl)-	13	528
	phenyl]-5,5-dimethyl-4-oxo-2-thioxoimi-
	dazolidin-1-yl]butyl]piperazine-1-carbothioate
590	S-Methyl 4-[4-[3-[4-cyano-3-(trifluoromethyl)-	13	542
	phenyl]-5,5-dimethyl-4-oxo-2-thioxoimi-
	dazolidin-1-yl]butyl]hexahydro-1H-1,4-
	diazepine-1-carbothioate
591	S-Ethyl 4-[4-[3-[4-cyano-3-(trifluoromethyl)-	13	542
	phenyl]-5,5-dimethyl-4-oxo-2-thioxoimi-
	dazolidin-1-yl]butyl]piperazine-1-carbothioate
592	N,N-Dimethyl 4-[4-[3-[4-cyano-3-	14	561
	(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]butyl]piperazine-1-
	sulfonamide

[0324]

TABLE 25
Compounds of General Formula I According to the Invention, in which
V = Trifluoromethylbenzonitrile, W = Thiohydantoin, n = 5
		Synthesis
		Anal-
Ex-		ogous
am-		to	ESI-
ple	Name	Example	MS
593	4-[3-[5-[4-(2-Methoxybenzoyl)piperazin-1-	4	602
	yl]pentyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
594	4-[5-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-	4	493
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]pentyl]piperazine-1-carbonitrile
595	4-[3-[5-(4-Acetylpiperazin-1-yl)pentyl]-4,4-		510
	dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
596	rel-4-[3-[5-[(2R,6S)-4-Acetyl-2,6-	4	538
	dimethylpiperazin-1-yl]pentyl]-4,4-dimethyl-5-
	oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
597	4-[3-[5-(4-Acetylhexahydro-1H-1,4-diazepin-1-	4	524
	yl)pentyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)benzonitrile
598	4-[4,4-Dimethyl-5-oxo-3-[5-[4-[1-oxopropyl)-	4	524
	piperazin-1-yl]-pentyl]-2-thioxoimidazolidin-1-
	yl]-2-(trifluoromethyl)-benzonitrile
599	4-[4,4-Dimethyl-3-[5-[4-(2-methyl-1-	4	538
	oxopropyl)-piperazin-1-yl]pentyl]-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
600	4-[3-[5-[Hexahydro-4-(2-methyl-1-oxopropyl)-	4	552
	1H-1,4-diazepin-1-yl]pentyl]-4,4-dimethyl-5-
	oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
601	4-[3-[5-[4-(2-Hydroxy-2-methyl-1-oxopropyl)-	4	554
	piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
602	4-[3-[5-[4-(2,2-Dimethyl-1-oxopropyl)piper-	4	552
	azin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
603	4-[3-[5-[4-(2,2-Dimethyl-1-oxopropyl)hexa-	4	566
	hydro-1H-1,4-diazepin-1-yl]pentyl]-4,4-
	dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)-benzonitrile
604	4-[4,4-Dimethyl-5-oxo-3-[5-[4-(1-oxobutyl)-	4	538
	piperazin-1-yl]-pentyl]-2-thioxoimidazolidin-1-
	yl]-2-(trifluoromethyl)-benzonitrile
605	4-[3-[5-[4-(Cyclopropylcarbonyl)piperazin-1-	4	536
	yl]pentyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
606	4-[3-[5-[4-(Cyclobutylcarbonyl)piperazin-1-	4	550
	yl]pentyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
607	4-[4,4-Dimethyl-5-oxo-3-[5-[4-[(thien-2-	4	592
	yl)acetyl]piperazin-1-yl]pentyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
608	4-[3-[5-[4-(Methoxyacetyl)piperazin-1-	4	540
	yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimi-
	dazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
609	4-[3-[5-[4-(3-Methoxy-1-oxopropyl)piperazin-	4	554
	1-yl]pentyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
610	4-[3-[5-[4-[(2-Methoxyethoxy)acetyl]piperazin-	4	584
	1-yl]pentyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
611	4-[3-[5-[4-[[2-(2-Methoxyethoxy)ethoxy]-	4	628
	acetyl]piperazin-1-yl]pentyl]-4,4-dimethyl-5-
	oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
612	4-[4,4-Dimethyl-5-oxo-2-thioxo-3-[5-[4-	4	564
	(trifluoroacetyl)piperazin-1-yl]pentyl]imi-
	dazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
613	4-[3-[5-[4-[(1,3-Dimethyl-1H-pyrazol-5-	4	590
	yl)carbonyl]-piperazin-1-yl]pentyl]-4,4-
	dimethyl-5-oxo-2-thioxo-imidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
614	4-[3-[5-[4-[(Furan-3-yl)carbonyl]piperazin-1-	4	562
	yl]pentyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
615	4-[3-[5-[4-[(Furan-3-yl)carbonyl]hexahydro-	4	576
	1H-1,4-diazepin-1-yl]pentyl]-4,4-dimethyl-5-
	oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
616	4-[3-[5-[4-[(2,5-Dimethylfuran-3-	4	590
	yl)carbonyl]piperazin-1-yl]pentyl]-4,4-
	dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)-benzonitrile
617	4-[3-[5-[4-[(Isoxazol-5-yl)carbonyl]piperazin-1-	4	563
	yl]pentyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
618	4-[4,4-Dimethyl-3-[5-[4-[(5-methylisoxazol-3-	4	577
	yl)carbonyl]-piperazin-1-yl]pentyl]-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
619	4-[4,4-Dimethyl-5-oxo-3-[5-[4-[(thien-3-	4	578
	yl)carbonyl]-piperazin-1-yl]pentyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
620	4-[3-[5-[Hexahydro-4-[(thien-3-yl)carbonyl]-	4	592
	1H-1,4-diazepin-1-yl]pentyl]-4,4-dimethyl-5-
	oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
621	4-[4,4-Dimethyl-3-[5-[4-[(4-methyl-1,2,3 -	4	594
	thiadiazol-4-yl)-carbonyl]piperazin-1-
	yl]pentyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
622	4-[3-[5-[4-[(Furan-2-yl)carbonyl]hexahydro-	4	576
	1H-1,4-diazepin-1-yl]pentyl]-4,4-dimethyl-5-
	oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
623	4-[4,4-Dimethyl-5-oxo-3-[5-[4-[(thien-2-	4	578
	yl)carbonyl]-piperazin-1-yl]pentyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
624	4-[3-[5-[Hexahydro-4-[(thien-2-yl)carbonyl]-	4	592
	1H-1,4-diazepin-1-yl]pentyl]-4,4-dimethyl-5-
	oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
625	4-[4,4-Dimethyl-5-oxo-3-[5-[4-[(pyridin-4-	4	573
	yl)carbonyl]-piperazin-1-yl]pentyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
626	4-[4,4-Dimethyl-3-[5-[4-(methylsulfonyl)piper-	5	546
	azin-1-yl]-pentyl]-5-oxo-2-thioxoimi-
	dazolidin-1-yl]-2-(trifluoromethyl)-benzonitrile
627	rel-4-[3-[5-[(2R,6S)-2,6-Dimethyl-4-	5	574
	(methylsulfonyl)piperazin-1-yl]pentyl]-4,4-
	dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
628	4-[3-[5-[Hexahydro-4-(methylsulfonyl)-1H-1,4-	5	560
	diazepin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
629	4-[3-[5-[4-(Ethylsulfonyl)piperazin-1-	5	560
	yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimi-
	dazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
630	4-[4,4-Dimethyl-5-oxo-3-[5-[4-(propyl-	5	574
	sulfonyl)-piperazin-1-yl]pentyl]-2-thioxoimi-
	dazolidin-1-yl]-2-(trifluoromethyl)-benzonitrile
631	4-[4,4-Dimethyl-5-oxo-3-[5-[4-(phenyl-	5	608
	sulfonyl)-piperazin-1-yl]pentyl]-2-thioxoimi-
	dazolidin-1-yl]-2-(trifluoromethyl)-benzonitrile
632	4-[3-[5-[4-[(4-Cyanophenyl)sulfonyl]piper-	5	633
	azin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
633	4-[3-[5-[4-[(2-Methoxyethoxy)sulfonyl]piper-	5	590
	azin-1-yl]-pentyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
634	4-[3-[5-[4-[[2-(2-Methoxyethoxy)ethyl]-	5	634
	sulfonyl]piperazin-1-yl]pentyl]-4,4-dimethyl-5-
	oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
635	4-[3-[5-[4-[[2-[2-(2-Methoxy-	5	678
	ethoxy)ethoxy]ethyl]-sulfonyl]-piperazin-1-
	yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxo-imida-
	zolidin-1-yl]-2-(trifluoromethyl)benzonitrile
636	4-[4,4-Dimethyl-3-[5-[4-[(1-methyl-1H-	5	612
	imidazol-4-yl)-sulfonyl]piperazin-1-yl]pentyl]-
	5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
637	4-[3-[5-[4-[(3,5-Dimethylisoxazol-4-	5	627
	yl)sulfonyl]piperazin-1-yl]pentyl]-4,4-dimethyl-
	5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
638	4-[5-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-	12	555
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]pentyl]-N-ethylpiperazine-1-carbothioamide
639	4-[5-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-	12	569
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]pentyl]-N-propylpiperazine-1-
	carbothioamide
640	4-[5-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-	12	567
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]pentyl]-N-(prop-2-enyl)-piperazine-1-
	carbothioamide
641	S-Methyl 4-[5-[3-[4-cyano-3-(trifluoromethyl)-	13	542
	phenyl]-5,5-dimethyl-4-oxo-2-thioxoimi-
	dazolidin-1-yl]pentyl]piperazine-1-carbothioate
642	S-Methyl 4-[5-[3-[4-cyano-3-(trifluoromethyl)-	13	556
	phenyl]-5,5-dimethyl-4-oxo-2-thioxoimi-
	dazolidin-1-yl]pentyl]hexahydro-1H-1,4-
	diazepin-1-carbothioate
643	S-Ethyl 4-[5-[3-[4-cyano-3-(trifluoromethyl)-	13	556
	phenyl]-5,5-dimethyl-4-oxo-2-thioxoimi-
	dazolidin-1-yl]pentyl]piperazine-1-carbothioate
644	N,N-Dimethyl 4-[5-[3-[4-cyano-3-	14	575
	(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]pentyl]piperazine-1-
	sulfonamide

[0325]

TABLE 26
Compounds of General Formula I According to the Invention, in which
V = Trifluoromethylbenzonitrile, W = Thiohydantoin, n = 6
		Synthesis
		Anal-
Ex-		ogous
am-		to	ESI-
ple	Name	Example	MS
645	4-[4,4-Dimethyl-3-[6-(4-methylpiperazin-1-	3	496
	yl)hexyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
646	4-[4,4-Dimethyl-3-[6-[4-(1-methylethyl)piper-	3	524
	azin-1-yl]-hexyl]-5-oxo-2-thioxoimi-
	dazolidin-1-yl]-2-(trifluoromethyl)-benzonitrile
647	4-[3-[6-[4-(2-Methoxybenzoyl)piperazin-1-	4	616
	yl]hexyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
648	4-[6-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-	4	507
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]hexyl]piperazine-1-carbonitrile
649	4-[3-[6-(4-Acetylpiperazin-1-yl)hexyl]-4,4-	4	524
	dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
650	rel-4-[3-[6-[(2R,5S)-4-Acetyl-2,5-dimethyl-	4	552
	piperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
651	rel-4-[3-[6-[(2R,6S)-4-Acetyl-2,6-dimethyl-	4	552
	piperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
652	4-[4,4-Dimethyl-5-oxo-3-[6-[4-(1-oxopropyl)-	4	538
	piperazin-1-yl]-hexyl]-2-thioxoimidazolidin-1-
	yl]-2-(trifluoromethyl)-benzonitrile
653	4-[4,4-Dimethyl-3-[6-[4-(2-methyl-1-	4	552
	oxopropyl)piperazin-1-yl]hexyl]-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
654	rel-4-[3-[6-[(2R,5S)-2,5-Dimethyl-4-(2-methyl-	4	580
	1-oxopropyl)piperazin-1-yl]hexyl]-4,4-
	dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoomethyl)-benzonitrile
655	4-[3-[6-[Hexahydro-4-(2-methyl-1-oxopropyl)-	4	566
	1H-1,4-diazepin-1-yl]hexyl]-4,4-dimethyl-5-
	oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
656	4-[3-[6-[4-(2-Hydroxy-2-methyl-1-oxopropyl)-	4	568
	piperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
657	4-[3-[6-[4-(2,2-Dimethyl-1-oxopropyl)piper-	4	566
	azin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
658	rel-4-[3-[6-[(2R,5S)-4-(2,2-Dimethyl-1-	4	594
	oxopropyl)-2,5-dimethylpiperazin-1-yl]hexyl]-
	4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-
	2-(trifluoromethyl)-benzonitrile
659	rel-4-[3-[6-[(2R,6S)-4-(2,2-Dimethyl-1-	4	594
	oxopropyl)-2,6-dimethylpiperazin-1-yl]hexyl]-
	4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-
	2-(trifluoromethyl)-benzonitrile
660	4-[4,4-Dimethyl-5-oxo-3-[6-[4-(1-	4	552
	oxobutyl)piperazin-1-yl]-hexyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
661	4-[3-[6-[4-(Cyclopropylcarbonyl)piperazin-1-	4	550
	yl]hexyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
662	rel-4-[3-[6-[(2R,5S)-4-(Cyclopropylcarbonyl)-	4	578
	2,5-dimethylpiperazin-1-yl]hexyl]-4,4-
	dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)-benzonitrile
663	4-[3-[6-[4-(Cyclobutylcarbonyl)piperazin-1-	4	564
	yl]hexyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
664	4-[3-[6-[4-(Methoxyacetyl)piperazin-1-	4	554
	yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimi-
	dazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
665	4-[3-[6-[4-(3-Methoxy-1-oxopropyl)piperazin-	4	568
	1-yl]hexyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
666	rel-4-[3-[6-[(2R,5S)-4-(3-Methoxy-1-	4	596
	oxopropyl)-2,5-dimethylpiperazin-1-yl]hexyl]-
	4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-
	2-(trifluoromethyl)-benzonitrile
667	4-[3-[6-[Hexahydro-4-(3-methoxy-1-oxo-	4	582
	propyl)-1H-1,4-diazepin-1-yl]hexyl]-4,4-
	dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)-benzonitrile
668	4-[3-[6-[4-[(2-Methoxyethoxy)acetyl]piperazin-	4	598
	1-yl]hexyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
669	4-[3-[6-[4-[[2-(2-Methoxyethoxy)ethoxy]-	4	642
	acetyl]piperazin-1-yl]hexyl]-4,4-dimethyl-5-
	oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
670	4-[4,4-Dimethyl-5-oxo-2-thioxo-3-[6-[4-	4	578
	(trifluoroacetyl)piperazin-1-yl]hexyl]imida-
	zolidin-1-yl]-2-(trifluoromethyl)benzonitrile
671	rel-4-[3-[6-[(2R,5S)-2,5-Dimethyl-4-	4	606
	(trifluoroacetyl)piperazin-1-yl]hexyl]-4,4-
	dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
672	4-[4,4-Dimethyl-5-oxo-3-[6-[4-[(thien-2-	4	606
	yl)acetyl]piperazin-1-yl]hexyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
673	rel-4-[3-[6-[(2R,5S)-4-[(Furan-3-yl)carbonyl]-	4	604
	2,5-dimethylpiperazin-1-yl]hexyl]-4,4-
	dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)-benzonitrile
674	rel-4-[3-[6-[(2R,5S)-4-[(Isoxazol-5-	4	605
	yl)carbonyl]-2,5-dimethylpiperazin-1-yl]hexyl]-
	4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-
	2-(trifluoromethyl)-benzonitrile
675	4-[3-[6-[4-[(Furan-2-yl)carbonyl]piperazin-1-	4	576
	yl]hexyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
676	rel-4-[3-[6-[(2R,5S)-4-[(Furan-2-yl)carbonyl]-	4	604
	2,5-dimethylpiperazin-1-yl]hexyl]-4,4-
	dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-
	2-(trifluoromethyl)-benzonitrile
677	4-[3-[6-[4-[(Furan-2-yl)carbonyl]hexahydro-	4	590
	1H-1,4-diazepin-1-yl]hexyl]-4,4-dimethyl-5-
	oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)-benzonitrile
678	4-[4,4-Dimethyl-5-oxo-3-[6-[4-[(thien-2-	4	592
	yl)carbonyl]-piperazin-1-yl]hexyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
679	rel-4-[3-[6-[(2R,5S)-2,5-Dimethyl-4-[(thien-2-	4	620
	yl)carbonyl]piperazin-1-yl]hexyl]-4,4-dimethyl-
	5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
680	4-[3-[6-[Hexahydro-4-[(thien-2-yl)carbonyl]-	4	606
	1H-1,4-diazepin-1-yl]hexyl]-4,4-dimethyl-5-
	oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
681	4-[4,4-Dimethyl-5-oxo-3-[6-[4-[(pyridin-4-	4	587
	yl)carbonyl]-piperazin-1-yl]hexyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
682	4-[4,4-Dimethyl-3-[6-[4-(methylsulfonyl)piper-	5	560
	azin-1-yl]-hexyl]-5-oxo-2-thioxoimi-
	dazolidin-1-yl]-2-(trifluoromethyl)-benzonitrile
683	rel-4-[3-[6-[(2R,5S)-2,5-Dimethyl-4-	5	588
	(methylsulfonyl)piperazin-1-yl]hexyl]-4,4-
	dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
684	rel-4-[3-[6-[(2R,6S)-2,6-Dimethyl-4-	5	588
	(methylsulfonyl)piperazin-1-yl]hexyl]-4,4-
	dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
685	4-[3-[6-[Hexahydro-4-(methylsulfonyl)-1H-1,4-	5	574
	diazepin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
686	4-[3-[6-[4-(Ethylsulfonyl)piperazin-1-yl]hexyl]-	5	574
	4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-
	2-(trifluoromethyl)benzonitrile
687	rel-4-[3-[6-[(2R,5S)-4-(Ethylsulfonyl)-2,5-	5	602
	dimethylpiperazin-1-yl]hexyl]-4,4-dimethyl-5-
	oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
688	4-[4,4-Dimethyl-5-oxo-3-[6-[4-(propyl-	5	588
	sulfonyl)-piperazin-1-yl]hexyl]-2-thioxoimi-
	dazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
689	4-[4,4-Dimethyl-3-[6-[4-[(1-methylethyl)-	5	588
	sulfonyl]piperazin-1-yl]hexyl]-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
690	4-[3-[6-[4-[(2-Methoxyethyl)sulfonyl]piper-	5	604
	azin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
691	4-[4,4-Dimethyl-5-oxo-3-[6-[4-(phenyl-	5	622
	sulfonyl)-piperazin-1-yl]hexyl]-2-thioxoimi-
	dazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
692	4-[3-[6-[4-[(4-Cyanophenyl)sulfonyl]piper-	5	647
	azin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
693	4-[6-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-	12	569
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]hexyl]-N-ethylpiperazine-1-carbothioamide
694	4-[6-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-	12	583
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]hexyl]-N-propylpiperazine-1-carbothioamide
695	4-[6-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-	12	581
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]hexyl]-N-(prop-2-enyl)-piperazine-1-
	carbothioamide
696	S-Methyl 4-[6-[3-[4-cyano-3-(trifluoromethyl)-	13	556
	phenyl]-5,5-dimethyl-4-oxo-2-thioxoimi-
	dazolidin-1-yl]hexyl]piperazine-1-carbothioate
697	S-Methyl 4-[6-[3-[4-cyano-3-(trifluoromethyl)-	13	570
	phenyl]-5,5-dimethyl-4-oxo-2-thioxoimi-
	dazolidin-1-yl]hexyl]hexahydro-1H-1,4-
	diazepine-1-carbothioate
698	S-Ethyl 4-[6-[3-[4-cyano-3-(trifluoromethyl)-	13	570
	phenyl]-5,5-dimethyl-4-oxo-2-thioxoimi-
	dazolidin-1-yl]hexyl]piperazine-1-
	carbothioate

[0326]

TABLE 27
Compounds of General Formula I According to the Invention, in which
V = Trifluoromethylbenzonitrile, W = Thiohydantoin, n = 7
		Synthesis
		Anal-
Ex-		ogous
am-		to	ESI-
ple	Name	Example	MS
699	4-[4,4-Dimethyl-3-[7-(4-methylpiperazin-1-	3	510
	yl)heptyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
700	4-[7-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-	4	521
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]heptyl]piperazine-1-carbonitrile
701	4-[3-[7-(4-Acetylpiperazin-1-yl)heptyl]-4,4-	4	538
	dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
702	rel-4-[3-[7-[(2R,6S)-4-Acetyl-2,6-dimethyl-	4	566
	piperazin-1-yl]heptyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
703	4-[3-[7-[4-(2-Hydroxy-2-methyl-1-oxopropyl)-	4	582
	piperazin-1-yl]heptyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
704	4-[3-[7-[4-(2,2-Dimethyl-1-oxopropyl)piper-	4	580
	azin-1-yl]heptyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
705	rel-4-[3-[7-[(2R,6S)-4-(2,2-Dimethyl-1-	4	608
	oxopropyl)2,6-dimethylpiperazin-1-yl]heptyl]-
	4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-
	2-(trifluoromethyl)-benzonitrile
706	4-[3-[7-[4-(Methoxyacetyl)piperazin-1-	4	568
	yl]heptyl]-4,4-dimethyl-5-oxo-2-thioxoimi-
	dazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
707	4-[4,4-Dimethyl-5-oxo-2-thioxo-3-[7-[4-	4	592
	(trifluoroacetyl)piperazin-1-yl]heptyl]imida-
	zolidin-1-yl]-2-(trifluoromethyl)benzonitrile
708	rel-4-[3-[7-[(2R,6S)-2,6-Dimethyl-4-	4	620
	(trifluoroacetyl)piperazin-1-yl]heptyl]-4,4-
	dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
709	4-[4,4-Dimethyl-3-[7-[4-(methylsulfonyl)piper-	5	574
	azin-1-yl]heptyl-5-oxo-2-thioxoimidazolidin-1-
	yl]-2-(trifluoromethyl)benzonitrile
710	rel-4-[3-[7-[(2R,6S)-2,6-Dimethyl-4-	5	602
	(methylsulfonyl)piperazin-1-yl]heptyl]-4,4-
	dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-
	(trifluoromethyl)benzonitrile
711	4-[3-[7-[4-[(2-Methoxyethyl)sulfonyl]piper-	5	618
	azin-1-yl]heptyl]-4,4-dimethyl-5-oxo-2-
	benzonitrile

[0327]

TABLE 28
Compounds of General Formula I According to the Invention, in which
V = Trifluoromethylbenzonitrile, W = Thiohydantoin, n = 8
		Synthesis
		Anal-
Ex-		ogous
am-		to	ESI-
ple	Name	Example	MS
712	4-[8-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-	4	535
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]octyl]piperazine-1-carbonitrile
713	rel-4-[3-[8-[(2R,6S)-4-Acetyl-2,6-	4	580
	dimethylpiperazin-1-yl]octyl]-4,4-dimethyl-5-
	oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)-benzonitrile
714	4-[4,4-Dimethyl-3-[8-[4-(2-methyl-1-	4	580
	oxopropyl)-piperazin-1-yl]octyl]-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
715	4-[3-[8-[4-(2-Hydroxy-2-methyl-1-oxopropyl)-	4	596
	piperazin-1-yl]octyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
716	rel-4-[3-[8-[(2R,6S)-4-(2,2-Dimethyl-1-	4	622
	oxopropyl)-2,6-dimethylpiperazin-1-yl]octyl]-
	4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-
	2-(trifluormethyl)benzonitril
717	4-[3-[8-[4-(Cyclopropylcarbonyl)piperazin-1-	4	578
	yl]octyl]-4,4-dimethyl-5-oxo-2-thioxoimi-
	dazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
718	4-[3-[8-[4-(Cyclobutylcarbonyl)piperazin-1-	4	592
	yl]octyl]-4,4-dimethyl-5-oxo-2-thioxoimi-
	dazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
719	4-[3-[8-[4-(Methoxyacetyl)piperazin-1-	4	582
	yl]octyl]-4,4-dimethyl-5-oxo-2-thioxoimi-
	dazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
720	4-[4,4-Dimethyl-5-oxo-2-thioxo-3-[8-[4-	4	606
	(trifluoroacetyl)piperazin-1-yl]octyl]imida-
	zolidin-1-yl]-2-(trifluoromethyl)benzonitrile
721	4-[4,4-Dimethyl-5-oxo-3-[8-[4-[(thien-2-	4	620
	yl)carbonyl]-piperazin-1-yl]octyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
722	4-[4,4-Dimethyl-5-oxo-3-[8-[4-[(pyridin-4-	4	615
	yl)carbonyl]-piperazin-1-yl]octyl]-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
723	4-[4,4-Dimethyl-3-[8-[4-(methylsulfonyl)piper-	5	588
	azin-1-yl]-octyl]-5-oxo-2-thioxoimidazolidin-1-
	yl]-2-(trifluoromethyl)-benzonitrile
724	4-[4,4-Dimethyl-5-oxo-3-[8-[4-(propyl-	5	616
	sulfonyl)-piperazin-1-yl]octyl]-2-thioxoimi-
	dazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
725	4-[4,4-Dimethyl-3-[8-[4-[(1-methylethyl)-	5	616
	sulfonyl]piperazin-1-yl]octyl]-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoromethyl)-
	benzonitrile
726	4-[3-[8-[4-[(2-Methoxyethyl)sulfonyl]piper-	5	632
	azin-1-yl]octyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)benzonitrile
727	4-[3-[8-[4-[(4-Cyanophenyl)sulfonyl]piper-	5	675
	azin-1-yl]octyl]-4,4-dimethyl-5-oxo-2-
	thioxoimidazolidin-1-yl]-2-(trifluoro-
	methyl)benzonitrile
728	4-[8-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-	12	597
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]octyl]-N-ethylpiperazine-1-carbothioamide
729	4-[8-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-	12	609
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]octyl]-N-(prop-2-enyl)-piperazine-1-
	carbothioamide
730	S-Methyl 4-[8-[3-[4-cyano-3-(trifluoromethyl)-	13	584
	phenyl]-5,5-dimethyl-4-oxo-2-thioxoimi-
	dazolidin-1-yl]octyl]piperazine-1-carbothioate
731	N,N-Dimethyl 4-[8-[3-[4-cyano-3-	14	617
	(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]octyl]piperazine-1-
	sulfonamide

[0328]

TABLE 29
Compounds of General Formula I According to the Invention, in which
V = Isobenzofuranone, W = Thiohydantoin, n = 3
		Synthesis
		Analogous
Ex-		to	ESI-
ample	Name	Example	MS
732	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	15 (4)	513
	5,5-dimethyl-1-[3-[4-[(thien-2-
	yl)carbonyl]piperazin-1-yl]propyl]-
	2-thioxoimidazolidin-4-one
733	3-[1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-	15 (4)	550
	[3-[4-[4-(dimethylamino)benzoyl]piperazin-
	1-yl]propyl]-5,5-dimethyl-2-
	thioxoimidazolidin-4-one
734	N-[(4-Chlorophenyl)methyl]-4-[3-[3-	15 (12)	586
	(1,3-dihydro-1-oxo-isobenzofuran-5-yl)-5,5-
	dimethyl-4-oxo-2-thioxo-imidazolidin-1-
	yl]propyl]piperazine-1-carbothioamide
735	S-Ethyl 4-[3-[3-(1,3-dihydro-1-oxoiso-	15 (13)	491
	benzofuran-5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]propyl]piperazine-
	1-carbothioate
736	4-[3-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-	15 (14)	502
	yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-
	1-yl]propyl]-N,N-diethylpiperazine-1-
	carboxylic acid amide

[0329]

TABLE 30
Compounds of General Formula I According to the Invention, in which
V = Isobenzofuranone, W = Thiohydantoin, n = 4
		Synthesis
		Analogous
Ex-		to	ESI-
ample	Name	Example	MS
737	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	4	527
	5,5-dimethyl-1-[4-[4-[(thien-2-
	yl)carbonyl]piperazin-1-yl]butyl]-2-thioxo-
	imidazolidin-4-one
738	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-	4	551
	[4-[4-(2-methoxybenzoyl)piperazin-1-
	yl]butyl]-5,5-dimethyl-2-thioxoimidazolidin-
	4-one
739	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-	4	564
	[4-[4-[4-(dimethylamino)benzoyl]piperazin-
	1-yl]butyl]-5,5-dimethyl-2-thioxoimida-
	zolidin-4-one
740	1-[4-[4-[(2,1,3-Benzothiadiazol-4-	5	615
	yl)sulfonyl]-piperazin-1-yl]butyl]-3-(1,3-
	dihydro-1-oxoisobenzofuran-5-yl)-5,5-
	dimethyl-2-thioxoimidazolidin-4-one
741	N-(2,6-Dichloropyridin-4-yl)-4-[4-[3-	6	606
	(1,3-dihydro-1-oxo-isobenzofuran-5-yl)-5,5-
	dimethyl-4-oxo-2-thioxo-imidazolidin-1-
	yl]butyl]piperazine-1-carboxylic acid amide
742	S-Methyl 4-[4-[3-(1,3-dihydro-1-oxoiso-	13	491
	benzofuran-5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]butyl]-
	piperazine-1-carbothioate
743	S-Ethyl 4-[4-[3-(1,3-dihydro-1-oxoiso-	13	505
	benzofuran-5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]butyl]piperazine-
	1-carbothioate

[0330]

TABLE 31
Compounds of General Formula I According to the Invention, in which
V = Isobenzofuranone, W = Thiohydantoin, n = 5
		Synthesis
		Analogous
Ex-		to	ESI-
ample	Name	Example	MS
744	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	4	501
	5,5-dimethyl-1-[5-[4-(2-methyl-1-
	oxopropyl)piperazin-1-yl]pentyl]-2-
	thioxoimidazolidin-4-one
745	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	4	555
	5,5-dimethyl-1-[5-[4-[(thien-2-
	yl)acetyl]piperazin-1-yl]pentyl]-2-thioxo-
	imidazolidin-4-one
746	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	4	541
	5,5-dimethyl-1-[5-[4-[(thien-2-
	yl)carbonyl]piperazin-1-yl]pentyl]-2-
	thioxo-imidazolidin-4-one
747	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-	5	523
	[5-[4-ethyl-sulfonyl)piperazin-1-yl]pentyl]-
	5,5-dimethyl-2-thioxo-imidazolidin-4-one
748	4-[[4-[5-[3-(1,3-Dihydro-1-oxoisobenzo-	5	596
	furan-5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]pentyl]piperazin-
	1-yl]sulfonyl]benzonitrile
749	S-Ethyl 4-[5-[3-(1,3-dihydro-1-oxoisobenzo-	13	519
	furan-5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]pentyl]piperazine-
	1-carbothioate

[0331]

TABLE 32
Compounds of General Formula I According to the Invention, in which
V = Isobenzofuranone, W = Thiohydantoin, n = 6
		Synthesis
		Analogous
Ex-		to	ESI-
ample	Name	Example	MS
750	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-	4	579
	[6-[4-(2-methoxybenzoyl)piperazin-1-
	yl]hexyl]-5,5-dimethyl-2-thioxoimidazolidin-
	4-one
751	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-	4	592
	[6-[4-[4-(dimethylamino)benzoyl]piperazin-
	1-yl]hexyl]-5,5-dimethyl-2-
	thioxoimidazolidin-4-one
752	3-[[4-[6-[3-(1,3-Dihydro-1-oxoisobenzo-	4	574
	furan-5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-
	yl]hexyl]piperazin-1-yl]carbonyl]benzonitrile
753	1-[6-(4-Acetylpiperazin-1-yl)hexyl]-3-(1,3-	4	487
	dihydro-1-oxo-isobenzofuran-5-yl)-5,5-
	dimethyl-2-thioxoimidazolidin-4-one
754	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	4	501
	5,5-dimethyl-1-[6-[4-(1-oxo-
	propyl)piperazin-1-yl]hexyl]-2-
	thioxoimidazolidin-4-one
755	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	4	515
	5,5-dimethyl-1-[6-[4-(2-methyl-1-
	oxopropyl)-piperazin-1-yl]hexyl]-2-
	thioxoimidazolidin-4-one
756	3-(1,3-Dihydro-1-oxoisobenzofuran-5-	4	515
	yl)-5,5-dimethyl-1-[6-[4-(1-
	oxobutyl)piperazin-1-yl]hexyl]-
	2-thioxo-imidazolidin-4-one
757	1-[6-[4-(Cyclopropylcarbonyl)piperazin-1-	4	513
	yl]hexyl]-3-(1,3-dihydro-1-oxoisobenzo-
	furan-5-yl)-5,5-dimethyl-2-
	thioxoimidazolidin-4-one
758	1-[6-[4-(Cyclobutylcarbonyl)piperazin-1-	4	527
	yl]hexyl]-3-(1,3-dihydro-1-oxoisobenzo-
	furan-5-yl)-5,5-dimethyl-2-thioxo-
	imidazolidin-4-one
759	3-(1,3-Dihydro-1-oxoisobenzofuran-5-	4	550
	yl)-5,5-dimethyl-1-[6-[4-[(pyridin-4-
	yl)carbonyl]piperazin-1-yl]hexyl]-
	2-thioxo-imidazolidin-4-one
760	3-(1,3-Dihydro-1-oxoisobenzofuran-5-	4	555
	yl)-5,5-dimethyl-1-[6-[4-[(thien-2-
	yl)carbonyl]piperazin-1-
	yl]hexyl]-2-thioxo-imidazolidin-4-one
761	3-(1,3-Dihydro-1-oxoisobenzo-	4	569
	furan-5-yl)-5,5-dimethyl-1-[6-[4-
	[(thien-2-yl)acetyl]piperazin-1-
	yl]hexyl]-2-thioxo-imidazolidin-4-one
762	3-(1,3-Dihydro-1-oxoisobenzofuran-5-	5	523
	yl)-5,5-dimethyl-1-[6-[4-(methyl-
	sulfonyl)piperazin-1-yl]hexyl]-2-thioxo-
	imidazolidin-4-one
763	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-	5	537
	[6-[4-(ethylsulfonyl)piperazin-1-
	yl]hexyl]-5,5-dimethyl-2-thioxo-
	imidazolidin-4-one
764	3-(1,3-Dihydro-1-oxoisobenzofuran-5-	5	551
	yl)-5,5-dimethyl-1-[6-[4-(propyl-
	sulfonyl)piperazin-1-yl]hexyl]-
	2-thioxo-imidazolidin-4-one
765	3-(1,3-Dihydro-1-oxoisobenzofuran-5-	5	585
	yl)-5,5-dimethyl-1-[6-[4-(phenyl-
	sulfonyl)piperazin-1-yl]hexyl]-
	2-thioxo-imidazolidin-4-one
766	4-[[4-[6-[3-(1,3-Dihydro-1-oxoisobenzo-	5	610
	furan-5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]hexyl]piperazin-1-
	yl]sulfonyl]benzonitrile
767	1-[6-[4-[(2,1,3-Benzothiadiazol-4-	5	643
	yl)sulfonyl]-piperazin-1-yl]hexyl]-3-(1,3-
	dihydro-1-oxoisobenzofuran-5-yl)-5,5-
	dimethyl-2-thioxoimidazolidin-4-one
768	4-[6-[3-(1,3-Dihydro-1-oxoisobenzofuran-	6	610
	5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]hexyl]-N-[3-
	(methylsulfanyl)phenyl]piperazine-
	1-carboxylic acid amide
769	4-[6-[3-(1,3-Dihydro-1-oxoisobenzofuran-	6	582
	5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]hexyl]-
	N-(3-fluorophenyl)piperazine-1-
	carboxylic acid amide
770	4-[6-[3-(1,3-Dihydro-1-oxoisobenzo-	6	582
	furan-5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]hexyl]-
	N-(4-fluorophenyl)piperazine-1-
	carboxylic acid amide
771	4-[6-[3-(1,3-Dihydro-1-oxoisobenzofuran-	12	532
	5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]hexyl]-N-ethyl-
	piperazine-1-carbothioamide
772	4-[6-[3-(1,3-Dihydro-1-oxoisobenzo-	12	546
	furan-5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-
	yl]hexyl]-N-propyl-piperazine-1-
	carbothioamide
773	4-[6-[3-(1,3-Dihydro-1-oxoisobenzo-	12	544
	furan-5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]hexyl]-N-
	(prop-2-enyl)piperazine-1-carbothioamide
774	4-[6-[3-(1,3-Dihydro-1-oxoisobenzofuran-	12	580
	5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-
	yl]hexyl]-N-phenyl-piperazine-1-
	carbothioamide
775	4-[6-[3-(1,3-Dihydro-1-oxoisobenzofuran-	12	594
	5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-
	yl]hexyl]-N-(phenylmethyl)piperazine-1-
	carbothioamide
776	S-Methyl 4-[6-[3-(1,3-dihydro-1-	13	519
	oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-
	2-thioxoimidazolidin-1-
	yl]hexyl]-piperazine-1-carbothioate
777	S-Ethyl 4-[6-[3-(1,3-dihydro-1-oxoiso-	13	533
	benzofuran-5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-
	yl]hexyl]piperazine-1-carbothioate
778	4-[6-[3-(1,3-Dihydro-1-oxoisobenzofuran-	14	544
	5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]hexyl]-
	N,N-diethylpiperazine-1-carboxylic acid
	amide

[0332]

TABLE 33
Compounds of General Formula I According to the Invention, in which
V = Isobenzofuranone, W = Thiohydantoin, n = 7
		Synthesis
		Analogous
Ex-		to	ESI-
ample	Name	Example	MS
779	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-	4	593
	[7-[4-(2-methoxybenzoyl)piperazin-1-
	yl]heptyl]-5,5-dimethyl-2-
	thioxoimidazolidin-4-one
780	1-[7-(4-Acetylpiperazin-1-yl)heptyl]-3-	4	501
	(1,3-dihydro-1-oxo-isobenzofuran-5-yl)-5,5-
	dimethyl-2-thioxoimidazolidin-4-one
781	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	4	515
	5,5-dimethyl-1-[7-[4-(1-
	oxopropyl)piperazin-1-yl]heptyl]-2-thioxo-
	imidazolidin-4-one
782	3-(1,3-Dihydro-1-oxoisobenzofuran-5-	4	529
	yl)-5,5-dimethyl-1-[7-[4-(2-methyl-1-
	oxopropyl)piperazin-1-yl]heptyl]-2-
	thioxoimidazolidin-4-one
783	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	4	529
	5,5-dimethyl-1-[7-[4-(1-
	oxobutyl)piperazin-1-yl]heptyl]-2-thioxo-
	imidazolidin-4-one
784	1-[7-[4-(Cyclopropyl-carbonyl)piperazin-1-	4	527
	yl]heptyl]-3-(1,3-dihydro-1-
	oxoisobenzofuran-5-yl)-5,5-
	dimethyl-2-thioxo-imidazolidin-4-one
785	1-[7-[4-(Cyclobutyl-carbonyl)piperazin-1-	4	541
	yl]heptyl]-3-(1,3-dihydro-1-
	oxoisobenzofuran-5-yl)-5,5-
	dimethyl-2-thioxo-imidazolidin-4-one
786	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	4	569
	5,5-dimethyl-1-[7-[4-[(thien-2-
	yl)carbonyl]piperazin-1-yl]heptyl]-2-
	thioxo-imidazolidin-4-one
787	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	4	583
	5,5-dimethyl-1-[7-[4-[(thien-2-
	yl)acetyl]piperazin-1-yl]heptyl]-2-
	thioxo-imidazolidin-4-one
788	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	5	537
	5,5-dimethyl-1-[7-[4-(methyl-
	sulfonyl)piperazin-1-yl]heptyl]-2-thioxo-
	imidazolidin-4-one
789	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	5	551
	1-[7-[4-(ethyl-sulfonyl)piperazin-1-
	yl]heptyl]-5,5-dimethyl-2-thioxo-
	imidazolidin-4-one
790	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	5	565
	5,5-dimethyl-1-[7-[4-(propyl-
	sulfonyl)piperazin-1-yl]heptyl]-2-thioxo-
	imidazolidin-4-one
791	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	5	599
	5,5-dimethyl-1-[7-[4-(phenyl-
	sulfonyl)piperazin-1-yl]heptyl]-2-thioxo-
	imidazolidin-4-one
792	4-[7-[3-(1,3-Dihydro-1-oxoisobenzo-	12	546
	furan-5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]heptyl]-N-ethyl-
	piperazine-1-carbothioamide
793	4-[7-[3-(1,3-Dihydro-1-oxoisobenzo-	12	560
	furan-5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]heptyl]-N-propyl-
	piperazine-1-carbothioamide
794	4-[7-[3-(1,3-Dihydro-1-oxoisobenzo-	12	558
	furan-5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]heptyl]-N-(prop-
	2-enyl)piperazine-1-carbothioamide
795	S-Methyl 4-[7-[3-(1,3-dihydro-1-	13	533
	oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-
	2-thioxoimidazolidin-1-yl]heptyl]-piperazine-
	1-carbothioate
796	S-Ethyl 4-[7-[3-(1,3-dihydro-1-oxoisobenzo-	13	547
	furan-5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]heptyl]piperazine-1-
	carbothioate

[0333]

TABLE 34
Compounds of General Formula I According to the Invention, in which
V = Isobenzofuranone, W = Thiohydantoin, n = 8
		Synthesis
		Analogous
Ex-		to	ESI-
ample	Name	Example	MS
797	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-	4	607
	[8-[4-(2-methoxybenzoyl)piperazin-1-
	yl]octyl]-5,5-dimethyl-2-
	thioxoimidazolidin-4-one
798	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-	4	620
	[8-[4-[4-(dimethyl-
	amino)benzoyl]piperazin-1-yl]octyl]-
	5,5-dimethyl-2-thioxoimidazolidin-4-one
799	1-[8-(4-Acetylpiperazin-1-yl)octyl]-3-(1,3-	4	515
	dihydro-1-oxo-isobenzofuran-5-yl)-5,5-
	dimethyl-2-thioxoimidazolidin-4-one
800	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	4	529
	5,5-dimethyl-1-[8-[4-(1-
	oxopropyl)piperazin-1-yl]octyl]-2-
	thioxo-imidazolidin-4-one
801	1-[8-[4-(Cyclopropylcarbonyl)piperazin-1-	4	541
	yl]octyl]-3-(1,3-dihydro-1-oxoisobenzo-
	furan-5-yl)-5,5-dimethyl-2-thioxo-
	imidazolidin-4-one
802	1-[8-[4-(Cyclobutylcarbonyl)piperazin-1-	4	555
	yl]octyl]-3-(1,3-dihydro-1-
	oxoisobenzofuran-5-yl)-5,5-dimethyl-2-
	thioxo-imidazolidin-4-one
803	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	4	583
	5,5-dimethyl-1-[8-[4-[(thien-2-
	yl)carbonyl]piperazin-1-yl]octyl]-2-thioxo-
	imidazolidin-4-one
804	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	4	597
	5,5-dimethyl-1-[8-[4-[(thien-2-
	yl)acetyl]piperazin-1-yl]octyl]-2-thioxo-
	imidazolidin-4-one
805	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	4	578
	5,5-dimethyl-1-[8-[4-[(pyridin-4-
	yl)carbonyl]piperazin-1-yl]octyl]-2-thioxo-
	imidazolidin-4-one
806	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	5	551
	5,5-dimethyl-1-[8-[4-(methyl-
	sulfonyl)piperazin-1-yl]octyl]-2-thioxo-
	imidazolidin-4-one
807	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-	5	565
	[8-[4-(ethylsulfonyl)piperazin-1-yl]octyl]-
	5,5-dimethyl-2-thioxo-imidazolidin-4-one
808	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	5	579
	5,5-dimethyl-1-[8-[4-(propyl-
	sulfonyl)piperazin-1-yl]octyl]-2-thioxo-
	imidazolidin-4-one
809	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	5	619
	5,5-dimethyl-2-thioxo-1-[8-[4-[(2,2,2-
	trifluoroethyl)-sulfonyl]piperazin-1-yl]-
	octyl]imidazolidin-4-one
810	3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-	5	613
	5,5-dimethyl-1-[8-[4-(phenyl-
	sulfonyl)piperazin-1-yl]octyl]-2-thioxo-
	imidazolidin-4-one
811	4-[8-[3-(1,3-Dihydro-1-oxoisobenzofuran-	6	638
	5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]octyl]-N-[3-
	(methylsulfanyl)phenyl]piperazine-
	1-carboxylic acid amide
812	4-[8-[3-(1,3-Dihydro-1-oxoisobenzofuran-	6	610
	5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]octyl]-N-(3-
	fluorophenyl)piperazine-1-carboxylic acid
	amide
813	4-[8-[3-(1,3-Dihydro-1-oxoisobenzofuran-	12	560
	5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]octyl]-N-
	ethylpiperazine-1-carbothioamide
814	4-[8-[3-(1,3-Dihydro-1-oxoisobenzofuran-	12	574
	5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]octyl]-N-
	propylpiperazine-1-carbothioamide
815	4-[8-[3-(1,3-Dihydro-1-oxoisobenzofuran-	12	572
	5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]octyl]-N-(prop-2-
	enyl)piperazine-1-carbothioamide
816	4-[8-[3-(1,3-Dihydro-1-oxoisobenzofuran-	12	622
	5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]octyl]-N-
	(phenylmethyl)piperazine-1-carbothioamide
817	4-[8-[3-(1,3-Dihydro-1-oxoisobenzofuran-	12	608
	5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]octyl]-N-(phenyl-
	piperazine-1-carbothioamide
818	S-Methyl 4-[8-[3-(1,3-dihydro-1-oxoiso-	13	547
	benzofuran-5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]octyl]-piperazine-
	1-carbothioate
819	S-Ethyl 4-[8-[3-(1,3-dihydro-1-oxoisobenzo-	13	561
	furan-5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]octyl]piperazine-1-
	carbothioate
820	4-[8-[3-(1,3-Dihydro-1-oxoisobenzo-	14	572
	furan-5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]octyl]-N,N-
	diethylpiperazine-1-carboxylic acid amide

[0334]

TABLE 35
Compounds of General Formula I According to the Invention, in which
V = Methylbenzoxazinone, W = Thiohydantoin, n = 5
		Synthesis
		Analogous
Ex-		to	ESI-
ample	Name	Example	MS
821	6-[4,4-Dimethyl-5-oxo-3-[5-[4-	5	536
	(methylsulfonyl)-piperazin-1-yl]pentyl]-2-
	thioxoimidazolidin-1-yl]-
	4-methyl-1H-2,3-benzoxazin-1-one

[0335]

TABLE 36
Compounds of General Formula I According to the Invention, in which
V = Methylbenzoxazinone, W = Thiohydantoin, n = 6
		Synthesis
		Analogous
Ex-		to	ESI-
ample	Name	Example	MS
822	6-[4,4-Dimethyl-5-oxo-3-[6-[4-	5	550
	(methylsulfonyl)-piperazin-1-yl]hexyl]-2-
	thioxoimidazolidin-1-yl]-
	4-methyl-1H-2,3-benzoxazin-1-one

[0336]

TABLE 37
Compounds of General Formula I According to the Invention, in which
V = Indanone, W = Thiohydantoin, n = 6
		Synthesis
		Analogous
Ex-		to	ESI-
ample	Name	Example	MS
823	1-[6-(4-Acetylpiperazin-1-yl)hexyl]-3-(2,3-	4	485
	dihydro-1-oxo-1H-inden-5-yl)-5,5-dimethyl-
	2-thioxoimidazolidin-4-one
824	3-(2,3-Dihydro-1-oxo-1H-inden-5-yl)-5,5-	4	513
	dimethyl-1-[6-[4-(2-methyl-1-
	oxopropyl)piperazin-1-yl]hexyl]-2-
	thioxoimidazolidin-4-one
825	3-(2,3-Dihydro-1-oxo-1H-inden-5-yl)-	4	553
	5,5-dimethyl-1-[6-[4-[(thien-2-
	yl)carbonyl]piperazin-1-yl]hexyl]-2-
	thioxoimidazolidin-4-one
826	3-(2,3-Dihydro-1-oxo-1H-inden-5-yl)-5,5-	4	548
	dimethyl-1-[6-[4-[(pyridin-4-
	yl)carbonyl]piperazin-1-yl]hexyl]-2-
	thioxoimidazolidin-4-one
827	3-(2,3-Dihydro-1-oxo-1H-inden-5-yl)-5,5-	5	521
	dimethyl-1-[6-[4-(methyl-
	sulfonyl)piperazin-1-yl]hexyl]-2-
	thioxoimidazolidin-4-one
828	3-(2,3-Dihydro-1-oxo-1H-inden-5-yl)-	5	549
	5,5-dimethyl-1-[6-[4-(propyl-
	sulfonyl)piperazin-1-yl]hexyl]-2-
	thioxoimidazolidin-4-one
829	4-[6-[3-(2,3-Dihydro-1-oxo-1H-inden-5-yl)-	12	530
	5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-
	yl]hexyl]-N-ethylpiperazine-1-
	carbothioamide
830	S-Methyl 4-[6-[3-(2,3-dihydro-1-oxo-1H-	13	517
	inden-5-yl)-5,5-dimethyl-4-oxo-2-
	thioxoimidazolidin-1-yl]hexyl]piperazine-
	1-carbothioate

[0337] The entire disclosures of all applications, patents and publications, cited herein and of corresponding Germany Application No. 101 59 035.0, filed Nov. 23, 2001, and Germany Application No. 102 38 742.7 of Aug. 19, 2002, and U.S. Provisional Application Serial No. 60/406,650, filed Aug. 29, 2002 and U.S. Provisional Application No. 60/383,785, filed May 30, 2002 are incorporated by references herein.

[0338] The preceding examples can be repeated with similar success by substituting the generically or specifically described reactants and/or operating conditions of this invention for those used in the preceding examples.

[0339] From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention and, without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions.

Claims

1. Compounds of general formula I, in which

2. Compounds of general formula I according to claim 1, characterized in that i=j=1.

3. Compounds of general formula I according to claim 1 or 2, wherein R and R′ mean H.

4. Compounds of general formula I according to one of claims 1 to 3, wherein T=carbon.

5. Compounds of general formula I according to one of claims 1 to 3, wherein T=nitrogen.

6. Compounds of general formula I according to claim 4, wherein

7. Compounds of general formula I according to claim 5, wherein

8. Compounds according to claim 1, namely 1,1-Dimethylethyl 4-[5-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]piperazine-1-carboxylate 4-[2,5-Dihydro-3-methyl-4-[5-[4-[2-(methylsulfanyl)phenyl]piperazin-1-yl]pentyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(4-Cyanobenzoyl)piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[(3-Fluorophenyl)sulfonyl]piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]-N-[4-(dimethylamino)phenyl]piperazine-1-carboxamide 4-[2,5-Dihydro-3-methyl-4-[3-[4-(1-methylethylsulfonyl)piperazin-1-yl]propyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[[4-(1-methylethylsulfonyl)piperazin-1-yl]methyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[7-[4-(1-methylethylsulfonyl)piperazin-1-yl]heptyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 1,1-Dimethylethyl 4-[5-[3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]pentyl]piperazine-1-carboxylate 4-[5-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]pentyl]-N-ethylpiperazine-1-carbothioamide S-Methyl 4-[5-[3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]pentyl]piperazine-1-carbothioate 4-[5-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]pentyl]-N,N-diethylpiperazine-1-carboxamide 4-[3-[2-[4-(2-Methoxybenzoyl)piperazin-1-yl]ethyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[(4-Acetylpiperazin-1-yl)methyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[[4-(methoxyacetyl)piperazin-1-yl]methyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[4-[[(2-methoxyethoxy)acetyl]piperazin-1-yl]methyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[[4-[[2-(2-methoxyethoxy)ethoxy]acetyl]piperazin-1-yl]methyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[[4-(2-methoxybenzoyl)piperazin-1-yl]methyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[[4-(methylsulfonyl)piperazin-1-yl]methyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[[4-(Ethylsulfonyl)piperazin-1-yl]methyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[[4-(2-methoxyethyl)sulfonyl]-piperazin-1-yl]methyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[[4-[[2-[2-(2-methoxyethoxy)ethoxy]ethyl]sulfonyl]piperazin-1-yl]methyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[[4-(phenylsulfonyl)piperazin-1-yl]methyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[2-(4-Acetylpiperazin-1-yl)ethyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[2-(4-(1-oxopropyl)piperazin-1-yl)ethyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[2-[4-(Cyclopropylcarbonyl)piperazin-1-yl]ethyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[2-[4-(methoxyacetyl)piperazin-1-yl]ethyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[2-[4-(3-methoxy-1-oxopropyl)piperazin-1-yl]ethyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[2-[4-[(2-methoxyethoxy)acetyl]piperazin-1-yl]ethyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[2-[4-[[2-(2-methoxyethoxy)ethoxy]acetyl]piperazin-1-yl]ethyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[2-[4-(2-methoxybenzoyl)piperazin-1-yl]ethyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[2-[4-(methylsulfonyl)piperazin-1-yl]ethyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[2-[4-(Ethylsulfonyl)piperazin-1-yl]ethyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[2-[4-(Cyclopropylsulfonyl)piperazin-1-yl]ethyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[2-[4-(2-methoxyethyl)sulfonyl]piperazin-1-yl]ethyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[2-[4-[[2-(2-methoxyethoxy)ethyl]sulfonyl]piperazin-1-yl]ethyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[2-[4-[[2-[2-(2-methoxyethoxy)ethoxy]ethyl]sulfonyl]-piperazin-1-yl]ethyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[2-[4-(phenylsulfonyl)piperazin-1-yl]ethyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[2-[4-[(phenylmethyl)sulfonyl]piperazin-1-yl]ethyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[2-[4-[(1-methyl-1H-imidazol-4-1)sulfonyl]piperazin-1-yl]ethyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]ethyl]-N-(1-methylethyl)piperazine-1-carboxamide 4-[2-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]ethyl]-N-ethylpiperazine-1-carbothioamide Methyl 4-[2-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]ethyl]piperazine-1-carboxylate S-Methyl 4-[2-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]ethyl]piperazine-1-carbothioate 4-[2-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]ethyl]-N,N-dimethylpiperazine-1-sulfonamide 4-[3-[3-(4-Acetylpiperazin-1-yl)propyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[3-(4-(1-oxopropyl)piperazin-1-yl)propyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[3-[4-(Cyclopropylcarbonyl)piperazin-1-yl]propyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[3-[4-(methoxyacetyl)piperazin-1-yl]propyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[3-[4-(3-methoxy-1-oxopropyl)piperazin-1-yl]propyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[3-[4-[(2-methoxyethoxy)acetyl]piperazin-1-yl]propyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[3-[4-[[2-(2-methoxyethoxy)ethoxy]acetyl]piperazin-1-yl]propyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[3-[4-(2-methoxybenzoyl)piperazin-1-yl]propyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[3-[4-(methylsulfonyl)piperazin-1-yl]propyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[3-[4-(Ethylsulfonyl)piperazin-1-yl]propyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[3-[4-(Cyclopropylsulfonyl)piperazin-1-yl]propyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[3-[4-(2-methoxyethyl)sulfonyl]piperazin-1-yl]propyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[3-[4-[[2-(2-methoxyethoxy)ethyl]sulfonyl]piperazin-1-yl]propyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[3-[4-[[2-[2-(2-methoxyethoxy)ethoxy]ethyl]-sulfonyl]piperazin-1-yl]propyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[3-[4-(phenyl-sulfonyl)piperazin-1-yl]propyl-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[3-[4-[(phenylmethyl)sulfonyl]piperazin-1-yl]propyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[3-[4-[(1-methyl-1H-imidazol-4-yl)sulfonyl]-piperazin-1-yl]propyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]propyl]-N-(1-methylethyl)-piperazine-1-carboxamide 4-[3-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]propyl]-N-ethylpiperazine-1-carbothioamide Methyl 4-[3-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]propyl]piperazine-1-carboxylate S-Methyl 4-[3-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]propyl]piperazine-1-carbothioate 4-[3-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]propyl]-N,N-dimethylpiperazine-1-sulfonamide 1,1-Dimethylethyl-4-[4-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]butyl]piperazine-1-carboxylate 4-[2,5-Dihydro-3-methyl-4-[4-[4-[2-(methylsulfanyl)phenyl]piperazin-1-yl]butyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(3,5-Dichloropyridin-4-yl)piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(Cyclopentylacetyl)piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(2,6-Difluorobenzoyl)piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(2,6-Dichlorobenzoyl)piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(3-Fluorobenzoyl)piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[4-[4-(3-methoxybenzoyl)piperazin-1-yl]butyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[4-[4-(3-methylbenzoyl)piperazin-1-yl]butyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(4-Fluorobenzoyl)piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[4-[4-[(naphthalen-1-yl)carbonyl]piperazin-1-yl]butyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[4-[4-[(naphthalen-2-yl)-carbonyl]piperazin-1-yl]butyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(3-Cyanobenzoyl)piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(Cyclohexylcarbonyl)piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-[(Furan-2-yl)carbonyl]piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(Cyclopentylcarbonyl)piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[4-[4-[(5-methylisoxazol-3-yl)carbonyl]piperazin-1-yl]butyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[4-[4-(phenylacetyl)piperazin-1-yl]butyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[4-[4-(2-methoxybenzoyl)piperazin-1-yl]butyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[4-[4-(methoxyacetyl)piperazin-1-yl]butyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(2-Chlorobenzoyl)piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(2-Fluorobenzoyl)piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-(4-Benzoylpiperazin-1-yl)butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(Cyclobutylcarbonyl)piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[4-[4-[(pyridin-3-yl)carbonyl]piperazin-1-yl]butyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[4-[4-[(pyridin-4-yl)carbonyl]piperazin-1-yl]butyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-[4-(Dimethylamino)benzoyl]piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[4-[4-[(phenylsulfanyl)acetyl]piperazin-1-yl]butyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[4-[4-(phenoxyacetyl)piperazin-1-yl]butyl]-1H-pyrrol-1-yl)-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[4-[4-[(thien-2-yl)carbonyl]piperazin-1-yl]butyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[4-[4-(3-phenyl-1-oxopropyl)piperazin-1-yl]butyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-[(1,3-Benzodioxol-5-yl)carbonyl]piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[4-[4-[(4-methoxyphenyl)acetyl]piperazin-1-yl]butyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[4-[4-(2-methylbenzoyl)piperazin-1-yl]butyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(4-Chlorobenzoyl)piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[4-[4-[(thien-2-yl)acetyl]piperazin-1-yl]butyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(3-Chlorobenzoyl)piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(4-Cyanobenzoyl)piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[4-[4-(3-methoxy-1-oxopropyl)piperazin-1-yl]butyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[4-[4-[(2-methoxyethoxy)acetyl]piperazin-1-yl]butyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[4-[4-[[2-(2-methoxyethoxy)ethoxy]acetyl]piperazin-1-yl]butyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4-[4-[4-(Cyclopropylsulfonyl)piperazin-1-yl]butyl]-2,5-dihydro-3-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[4-[4-(2-methoxyethyl)sulfonyl]piperazin-1-yl]butyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[4-[4-[[2-(2-methoxyethoxy)ethyl]sulfonyl]piperazin-1-yl]butyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[4-[4-[[2-[2-(2-methoxyethoxy)ethoxy]-ethyl]sulfonyl]piperazin-1-yl]butyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]butyl]-N,N-dimethylpiperazine-1-sulfonamide 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[4-[4-(phenylsulfonyl)piperazin-1-yl]butyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[4-[4-(methylsulfonyl)piperazin-1-yl]butyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[4-[4-[(4-methylphenyl)sulfonyl]piperazin-1-yl]butyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile N-[4-[[4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]butyl]piperazin-1-y]sulfonyl]phenyl]acetamide 4-[3-[4-[4-[(4-Chlorophenyl)sulfonyl]piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-[(4-Cyanophenyl)sulfonyl]piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[4-[4-[(naphthalen-2-yl)sulfonyl]piperazin-1-yl]butyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-[(Quinolin-8-yl)sulfonyl]piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-[(2-Cyanophenyl)sulfonyl]piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-(3-[4-[4-[(3-Cyanophenyl)sulfonyl]piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-[(3,5-Dimethylisoxazol-4-yl)sulfonyl]piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-[(5-Chloro-1,3-dimethyl-1H-pyrazol-4-yl)sulfonyl]piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[4-[4-[(1-methyl-1H-imidazol-4-yl)sulfonyl]-piperazin-1-yl]butyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(Butylsulfonyl)piperazin-1-yl]butyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]butyl]-N-phenylpiperazine-1-carboxamide 4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]butyl]-N-(naphthalen-1-yl)piperazine-1-carboxamide 4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]butyl]-N-(naphthalen-2-yl)piperazine-1-carboxamide N-(2-Chlorophenyl)-4-[4-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]butyl]piperazine-1-carboxamide 4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]butyl]-N-[2-(trifluoromethyl)phenyl]piperazine-1-carboxamide 4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]butyl]-N-(3-methoxyphenyl)piperazine-1-carboxamide N-(4-Chlorophenyl)-4-[4-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]butyl]piperazine-1-carboxamide 4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]butyl]-N-(4-phenoxyphenyl)piperazine-1-carboxamide 4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]butyl]-N-[4-(methylsulfanyl)phenyl]piperazine-1-carboxamide N-[(1,1′-Biphenyl]-2-yl)-4-[4-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]butyl]piperazine-1-carboxamide 4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]butyl]-N-(2,5-dimethoxyphenyl)piperazine-1-carboxamide 4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]butyl]-N-[2-(1-methylethyl)phenyl]piperazine-1-carboxamide 4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]butyl]-N-(2,4,6-trimethylphenyl)piperazine-1-carboxamide (R)-4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]butyl]-N-(1-phenylethyl)piperazine-1-carboxamide 4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]butyl]-N-[2-(1,1-dimethylethyl)phenyl]piperazine-1-carboxamide 4-[4-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]butyl]-N-hexylpiperazine-1-carboxamide 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-(pyrazin-2-yl)piperazin-1-yl]pentyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(2,4-Difluorophenyl)piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[(Furan-2-yl)carbonyl]piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[5-[4-[(5-methylisoxazol-3-yl)carbonyl]piperazin-1-yl]pentyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-(phenylacetyl)piperazin-1-yl]pentyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[5-[4-(4-methoxybenzoyl)piperazin-1-yl]pentyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[5-[4-(2-methoxybenzoyl)piperazin-1-yl]pentyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[5-[4-(methoxyacetyl)piperazin-1-yl]pentyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(2-Chlorobenzoyl)piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(2-Fluorobenzoyl)piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-(4-Benzoylpiperazin-1-yl)pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(Cyclobutylcarbonyl)piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(3,4-Dimethoxybenzoyl)piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-[(pyridin-3-yl)carbonyl]piperazin-1-yl]pentyl]-1H-pyrrol-1-yl]-2-(trifluomethyl)benzonitrile 4-[3-[5-[4-(Cyclopropylcarbonyl)piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-[(pyridin-4-yl)carbonyl]piperazin-1-yl]pentyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[4-(Dimethylamino)benzoyl]piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-[(phenylsulfanyl)acetyl]piperazin-1-yl]pentyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-(phenoxyacetyl)piperazin-1-yl]pentyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-[(thien-2-yl)carbonyl]piperazin-1-yl]pentyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-(3-phenyl-1-oxopropyl)piperazin-1-yl]pentyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[(1,3-Benzodioxol-5-yl)carbonyl]piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[5-[4-[(4-methoxyphenyl)acetyl]piperazin-1-yl]pentyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[5-[4-(2-methylbenzoyl)piperazin-1-yl]pentyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-[(thien-2-yl)acetyl]piperazin-1-yl]pentyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[(4-Chlorophenoxy)acetyl]piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(3-Cyclopentyl-1-oxopropyl)piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(3-Chlorobenzoyl)piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(3,3-Dimethyl-1-oxobutyl)piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[5-[4-(3-methyl-1-oxobutyl)piperazin-1-yl]pentyl]-2,5-dioxo-1H-pyrrol-1-yl)-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-4-methyl-2,5-dioxo-3-[5-[4-[(phenylmethoxy)acetyl]piperazin-1-yl]pentyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(Cyclopentylacetyl)piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(2,6-Difluorobenzoyl)piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(2,6-Dichlorobenzoyl)piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-[2-trifluoromethyl)benzoyl]piperazin-1-yl]pentyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(3-Fluorobenzoyl)piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-[3-trifluoromethyl)benzoyl]piperazin-1-yl]pentyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[5-[4-(4-methylbenzoyl)piperazin-1-yl]pentyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[5-[4-[(naphthalen-1-yl)carbonyl]piperazin-1-yl]pentyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[5-[4-[(naphthalen-2-yl)carbonyl]piperazin-1-yl]pentyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(3-Cyanobenzoyl)piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(Cyclohexylcarbonyl)piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-(4-Acetylpiperazin-1-yl)pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[5-[4-(3-methoxy-1-oxopropyl)piperazin-1-yl]pentyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[5-[4-[(2-methoxyethoxy)acetyl]piperazin-1-yl]pentyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[5-[4-[[2-(2-methoxyethoxy)ethoxy]acetyl]piperazin-1-yl]pentyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4-[5-[4-(Cyclopropylsulfonyl)piperazin-1-yl]pentyl]-2,5-dihydro-3-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[5-[4-(2-methoxyethyl)sulfonyl]piperazin-1-yl]pentyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[5-[4-[[2-(2-methoxyethoxy)ethyl]sulfonyl]piperazin-1-yl]pentyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[5-[4-[[2-[2-(2-methoxyethoxy)ethoxy]-ethyl]sulfonyl]piperazin-1-yl]pentyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]-N,N-dimethylpiperazine-1-sulfonamide 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-[(1-methylethyl)sulfonyl]piperazin-1-yl]pentyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-(phenylsulfonyl)piperazin-1-yl]pentyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[5-[4-(methylsulfonyl)piperazin-1-yl]pentyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[(4-Chlorophenyl)sulfonyl]piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[5-[4-[(phenylmethyl)sulfonyl]piperazin-1-yl]pentyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[(4-Cyanophenyl)sulfonyl]piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4-[5-[4-[(Quinolin-8-yl)sulfonyl]piperazin-1-yl]pentyl]-2,5-dihydro-3-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[(2-Fluorophenyl)sulfonyl]piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[(2,5-Dimethoxyphenyl)sulfonyl]piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[(3-Cyanophenyl)sulfonyl]piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[(2,1,3-Benzothiadiazol-4-yl)sulfonyl]piperazin-1-yl]pentyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1-pyrrol-3-yl]pentyl]-N-(1,1-dimethylethyl)piperazine-1-carboxamide 4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]-N-(naphthalen-1-yl)piperazine-1-carboxamide N-(4-Cyanophenyl)-4-[5-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]piperazine-1-carboxamide N-(2-Chlorophenyl)-4-[5-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]piperazine-1-carboxamide 4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]-N-[2-(trifluoromethyl)phenyl]piperazine-1-carboxamide 4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]-N-(2-methylphenyl)piperazine-1-carboxamide 4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]-N-(3-methylphenyl)piperazine-1-carboxamide 4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]-N-(4-fluorophenyl)piperazine-1-carboxamide 4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]-N-(4-methoxyphenyl)piperazine-1-carboxamide N-(3-Cyanophenyl)-4-[5-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]piperazine-1-carboxamide 4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]-N-(3,5-dimethoxyphenyl)piperazine-1-carboxamide 4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]-N-(2-phenylethyl)piperazine-1-carboxamide N-([1,1′-Biphenyl]-2-yl)-4-[5-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]piperazine-1-carboxamide 4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]-N-[2-(1-methylethyl)phenyl]piperazine-1-carboxamide 4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]-N-(2,6-dichloropyridin-4-yl)piperazine-1-carboxamide (R)-4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]-N-(1-phenylethyl)piperazine-1-carboxamide 4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]-N-[3-[(trifluoromethyl)sulfanyl]phenyl]piperazine-1-carboxamide 4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]-N-[(3-methylphenyl)methyl]piperazine-1-carboxamide 4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]-N-[(4-methoxyphenyl)methyl]piperazine-1-carboxamide 4-[5-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]-N-(1,1,3,3-tetramethylbutyl)piperazine-1-carboxamide 1,1-Dimethylethyl 4-[6-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]piperazine-1-carboxylate 4-[2,5-Dihydro-3-methyl-4-[6-(4-methylpiperazin-1-yl)hexyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile Ethyl 4-[6-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]piperazine-1-carboxylate 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-(pyridin-2-yl)piperazin-1-yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile (Phenylmethyl) 4-[6-[1-[4-cyano-3-(trifluoromethyl)phenyl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]piperazine-1-carboxylate 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-(pyrimidin-2-yl)piperazin-1-yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[6-[4-(2-methoxyphenyl)piperazin-1-yl]hexyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[6-[4-(2-nitrophenyl)piperazin-1-yl]hexyl]-2,5-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-(pyrazin-2-yl)piperazin-1-yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[6-[4-[2-(methylsulfanyl)phenyl]piperazin-1-yl]hexyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-[3-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[6-[4-(2-methoxyethyl)piperazin-1-yl]hexyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(3,5-Dichloropyridin-4-yl)piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-(4-Acetylpiperazin-1-yl)hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-[(Furan-2-yl)carbonyl]piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-[(tetrahydrofuran-2-yl)carbonyl]piperazin-1-yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(Cyclopentylcarbonyl)piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[6-[4-[(5-methylisoxazol-3-yl)carbonyl]piperazin-1-yl]hexyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-(phenylacetyl)piperazin-1-yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[6-[4-(4-methoxybenzoyl)piperazin-1-yl]hexyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[6-[4-(2-methoxybenzoyl)piperazin-1-yl]hexyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[6-[4-(methoxyacetyl)piperazin-1-yl]hexyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(2-Chlorobenzoyl)piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(2-Fluorobenzoyl)piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-(4-Benzoylpiperazin-1-yl)hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(Cyclobutylcarbonyl)piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(3,4-Dimethoxybenzoyl)piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-[(phenylsulfanyl)acetyl]piperazin-1-yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-(phenoxyacetyl)piperazin-1-yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-[(thien-2-yl)carbonyl]piperazin-1-yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-(3-phenyl-1-oxopropyl)piperazin-1-yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-[(1,3-Benzodioxol-5-yl)carbonyl]piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[6-[4-[(4-methoxyphenyl)acetyl]piperazin-1-yl]hexyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[6-[4-(2-methylbenzoyl)piperazin-1-yl]hexyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(4-Chlorobenzoyl)piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-[(thien-2-yl)acetyl]piperazin-1-yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-[(4-Chlorophenoxy)acetyl]piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(3-Cyclopentyl-1-oxopropyl)piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(3-Chlorobenzoyl)piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-[4-trifluoromethyl)benzoyl]piperazin-1-yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(4-cyanobenzoyl)piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(3,3-Dimethyl-1-oxobutyl)piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[6-[4-(3-methyl-1-oxobutyl)piperazin-1-yl]hexyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-[(phenylmethoxy)acetyl]piperazin-1-yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(Cyclopentylacetyl)piperazin-1-yl]hexyl-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(2,6-Difluorobenzoyl)piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(2,6-Dichlorobenzoyl)piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-[2-trifluoromethyl)benzoyl]piperazin-1-yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(3-Fluorobenzoyl)piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[6-[4-(3-methoxybenzoyl)piperazin-1-yl]hexyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-[3-trifluoromethyl)benzoyl]piperazin-1-yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[6-[4-(3-methylbenzoyl)piperazin-1-yl]hexyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(4-Fluorobenzoyl)piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[6-[4-(4-methylbenzoyl)piperazin-1-yl]hexyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[6-[4-[(naphthalen-1-yl)carbonyl]piperazin-1-yl]hexyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[6-[4-[(naphthalen-2-yl)carbonyl]piperazin-1-yl]hexyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(3-Cyanobenzoyl)piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(Cyclohexylcarbonyl)piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[6-[4-(3-methoxy-1-oxopropyl)piperazin-1-yl]hexyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[6-[4-[(2-methoxyethoxy)acetyl]piperazin-1-yl]hexyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[6-[4-[[2-(2-methoxyethoxy)ethoxy]acetyl]piperazin-1-yl]hexyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4-[6-[4-(Cyclopropylsulfonyl)piperazin-1-yl]hexyl]-2,5-dihydro-3-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[6-[4-(2-methoxyethyl)sulfonyl]piperazin-1-yl]hexyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[6-[4-[[2-(2-methoxyethoxy)ethyl]sulfonyl]piperazin-1-yl]hexyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[6-[4-[[2-[2-(2-methoxyethoxy)ethoxy]ethyl]sulfonyl]-piperazin-1-yl]hexyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N,N-dimethylpiperazine-1-sulfonamide 4-[3-[6-[4-[[4-(1,1-Dimethylethyl)phenoxy]acetyl]-piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-(phenylsulfonyl)piperazin-1-yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[6-[4-(methylsulfonyl)piperazin-1-yl]hexyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[6-[4-[(4-methylphenyl)-sulfonyl]piperazin-1-yl]hexyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile N-[4-[[4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]piperazin-1-yl]sulfonyl]phenyl]acetamide 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-[(phenylmethyl)sulfonyl]piperazin-1-yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-[(4-Cyanophenyl)sulfonyl]piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[6-[4-[(naphthalen-2-yl)sulfonyl]piperazin-1-yl]hexyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-[[5-(Dimethylamino)naphthalen-1-yl]sulfonyl]piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-[(thien-2-yl)sulfonyl]piperazin-1-yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-[(Quinolin-8-yl)sulfonyl]piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-[(2-Fluorophenyl)sulfonyl]piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-[(2-Chlorophenyl)sulfonyl]piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-[(2-Cyanophenyl)sulfonyl]piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-[(3-Cyanophenyl)sulfonyl]piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[6-[4-[[5-[2-methyl-5-(trifluoromethyl)-2H-pyrazol-3-yl]thien-2-yl]sulfonyl]piperazin-1-yl]hexyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-[[1,2,3,4-tetrahydro-2-(trifluoroacetyl)isoquinolin-7-yl]sulfonyl]piperazin-1-yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-[(3,5-Dimethylisoxazol-4-yl)sulfonyl]piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-[(5-Chloro-1,3-dimethyl-1H-pyrazol-4-yl)sulfonyl]piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[6-[4-[(1-methyl-1H-imidazol-4-yl)sulfonyl]-piperazin-1-yl]hexyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(1,1-dimethylethyl)piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-phenylpiperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(naphthalen-1-yl)piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(naphthalen-2-yl)piperazine-1-carboxamide N-(4-Cyanophenyl)-4-[6-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(1-methylethyl)piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[3-(trifluoromethyl)phenyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(2-fluorophenyl)piperazine-1-carboxamide N-(2-Chlorophenyl)-4-[6-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(2-methoxyphenyl)piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[2-(trifluoromethyl)phenyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(2-methylphenyl)piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(3-fluorophenyl)piperazine-1-carboxamide N-(3-Chlorophenyl)-4-[6-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(3-methoxyphenyl)piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(3-methylphenyl)piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(4-fluorophenyl)piperazine-1-carboxamide N-(4-Chlorophenyl)-4-[6-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(4-methoxyphenyl)piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[4-(trifluoromethyl)phenyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(4-methylphenyl)piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(prop-2-enyl)piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-cyclohexylpiperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(phenylmethyl)piperazine-1-carboxamide N-(3-Cyanophenyl)-4-[6-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(3,5-dimethoxyphenyl)piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[3-(methylsulfanyl)phenyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(4-phenoxyphenyl)piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[4-(methylsulfanyl)phenyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[4-(1-methylethyl)phenyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(2-phenylethyl)piperazine-1-carboxamide N-([1,1′-Biphenyl]-2-yl)-4-[6-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[4-(phenylmethoxy)phenyl]piperazine-1-carboxamide N-(2-Cyanophenyl)-4-[6-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[2-(thien-2-yl)ethyl]piperazine-1-carboxamide (1R-trans)-4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(2-phenylcyclopropyl)piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(2,6-difluorophenyl)piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(2,6-dichlorophenyl)piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(2,4-dimethoxyphenyl)piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(2,5-dimethoxyphenyl)piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(2,6-dimethylphenyl)piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(trichloroacetyl)piperazine-1-carboxamide (S)-4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(1-phenylethyl)piperazine-1-carboxamide (R)-4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[1-(naphthalen-1-yl)ethyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(2,4,6-trichlorophenyl)piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[2-(1-methylethyl)phenyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(3,5-dichlorophenyl)piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(2,4,6-trimethylphenyl)piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[4-[(trifluoromethyl)sulfanyl]phenyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[(2,4-dichlorophenyl)methyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[2-(methylsulfanyl)phenyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(2,6-dichloropyridin-4-yl)piperazine-1-carboxamide (R)-4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexy]-N-(1-phenylethyl)piperazine-1-carboxamide (S)-4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[1-(naphthalen-1-yl)ethyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[1-methyl-1-[3-(1-methylethenyl)phenyl]ethyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[2-(trifluoromethoxy)phenyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(tricyclo[3.3.1.13,7]dec-1-yl)piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[4-(dimethylamino)phenyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[3-[(trifluoromethyl)sulfanyl]phenyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[(2-methylphenyl)methyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[(3-methylphenyl)methyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[(4-methylphenyl)methyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[(4-methoxyphenyl)methyl]piperazine-1-carboxamide 4-[6-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(1,1,3,3-tetramethylbutyl)piperazine-1-carboxamide 4-[3-[7-(4-Acetylpiperazin-1-yl)heptyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[7-(4-(1-oxopropyl)piperazin-1-yl)heptyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[7-[4-(Cyclopropylcarbonyl)piperazin-1-yl]heptyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[7-[4-(methoxyacetyl)piperazin-1-yl]heptyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[7-[4-(3-methoxy-1-oxopropyl)piperazin-1-yl]heptyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[7-[4-[(2-methoxyethoxy)acetyl]piperazin-1-yl]heptyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[7-[4-[[2-(2-methoxyethoxy)ethoxy]acetyl]piperazin-1-yl]heptyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[7-[4-(2-methoxybenzoyl)piperazin-1-yl]heptyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[7-[4-(methylsulfonyl)piperazin-1-yl]heptyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[7-[4-(Ethylsulfonyl)piperazin-1-yl]heptyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[7-[4-(Cyclopropylsulfonyl)piperazin-1-yl]heptyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[7-[4-(2-methoxyethyl)sulfonyl]piperazin-1-yl]heptyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[7-[4-[[2-(2-methoxyethoxy)ethyl]sulfonyl]piperazin-1- yl]heptyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[7-[4-[[2-[2-(2-methoxyethoxy)ethoxy]ethyl]sulfonyl]-piperazin-1-yl]heptyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[7-[4-(phenylsulfonyl)piperazin-1-yl]heptyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[7-[4-[(phenylmethyl)sulfonyl]piperazin-1-yl]heptyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[7-[4-[(1-methyl-1H-imidazol-4-yl)sulfonyl]-piperazin-1-yl]heptyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[7-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]heptyl]-N-(1-methylethyl)piperazine-1-carboxamide 4-[7-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]heptyl]-N-ethylpiperazine-1-carbothioamide Methyl 4-[7-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]heptyl]piperazine-1-carboxylate S-Methyl 4-[7-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]heptyl]piperazine-1-carbothioate 4-[7-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]heptyl]-N,N-dimethylpiperazine-1-sulfonamide 4-[3-[8-(4-Acetylpiperazin-1-yl)octyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[8-(4-(1-oxopropyl)piperazin-1-yl)octyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[8-[4-(Cyclopropylcarbonyl)piperazin-1-yl]octyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[8-[4-(methoxyacetyl)piperazin-1-yl]octyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[8-[4-(3-methoxy-1-oxopropyl)piperazin-1-yl]octyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[8-[4-[(2-methoxyethoxy)acetyl]piperazin-1-yl]octyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[8-[4-[[2-(2-methoxyethoxy)ethoxy]acetyl]piperazin-1-yl]octyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[8-[4-(2-methoxybenzoyl)piperazin-1-yl]octyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[8-[4-(methylsulfonyl)piperazin-1-yl]octyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[8-[4-(Ethylsulfonyl)piperazin-1-yl]octyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[8-[4-(Cyclopropylsulfonyl)piperazin-1-yl]octyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[8-[4-(2-methoxyethyl)sulfonyl]piperazin-1-yl]octyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[8-[4-[[2-(2-methoxyethoxy)ethyl]sulfonyl]piperazin-1-yl]octyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-[8-[4-[[2-[2-(2-methoxyethoxy)ethoxy]-ethyl]sulfonyl]piperazin-1-yl]octyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[8-[4-(phenylsulfonyl)piperazin-1-yl]octyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[8-[4-[(phenylmethyl)sulfonyl]piperazin-1-yl]octyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2,5-Dihydro-3-methyl-4-[8-[4-[(1-methyl-1H-imidazol-4-yl)sulfonyl]-piperazin-1-yl]octyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile 4-[8-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]octyl]-N-(1-methylethyl)piperazine-1-carboxamide 4-[8-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]octyl]-N-ethylpiperazine-1-carbothioamide Methyl 4-[8-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]octyl]piperazine-1-carboxylate S-Methyl 4-[8-[1-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]octyl]piperazine-1-carbothioate 4-[8-[1-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]octyl]-N,N-dimethylpiperazine-1-sulfonamide N-[4-[2,5-Dihydro-3-[6-[4-(2-methoxybenzoyl)piperazin-1-yl]hexyl]-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)phenyl]acetamide N-[4-[3-[6-[4-(Cyclobutylcarbonyl)piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)phenyl]acetamide N-[4-[2,5-Dihydro-3-methyl-2,5-dioxo-4-[6-[4-[(thien-2-yl)-carbonyl]piperazin-1-yl]hexyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)phenyl]acetamide N-[4-[3-[6-[4-[4-(Dimethylamino)benzoyl]piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)phenyl]acetamide N-[4-[3-[6-(4-Acetylpiperazin-1-yl)hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)phenyl]acetamide N-[4-[2,5-Dihydro-3-methyl-4-[6-[4-(methylsulfonyl)piperazin-1-yl]hexyl]-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)phenyl]acetamide N-[4-[3-[6-[4-[(2,1,3-Benzothiadiazol-4-yl)sulfonyl]piperazin-1-yl]hexyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl]-2-(trifluoromethyl)phenyl]acetamide 4-[6-[1-[4-(Acetylamino)-3-(trifluoromethyl)phenyl]-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(pyridin-4-yl)piperazine-1-carboxamide 3-[6-[4-(Cyclobutylcarbonyl)piperazin-1-yl]hexyl]-4-methyl-1-[4-nitro-3-(trifluoromethyl)phenyl]-1H-pyrrole-2,5-dione 3-[6-[4-[4-(Dimethylamino)benzoyl]piperazin-1-yl]hexyl]-4-methyl-1-[4-nitro-3-(trifluoromethyl)phenyl]-1H-pyrrole-2,5-dione 3-[6-(4-Acetylpiperazin-1-yl)hexyl]-4-methyl-1-[4-nitro-3-(trifluoromethyl)-phenyl]-1H-pyrrole-2,5-dione 3-Methyl-4-[6-[4-(methylsufonyl)piperazin-1-yl]hexyl]-1-[4-nitro-3-(trifluoromethyl)phenyl]-1H-pyrrole-2,5-dione 3-[6-[4-[(2,1,3-Benzothiadiazol-4-yl)sulfonyl]piperazin-1-yl]hexyl]-4-methyl-1-[4-nitro-3-(trifluoromethyl)phenyl]-1H-pyrrole-2,5-dione 1-[3,4-Bis(trifluoromethyl)phenyl]-3-[6-[4-(2-methoxybenzoyl)piperazin-1-yl]hexyl]-4-methyl-1H-pyrrole-2,5-dione 3-[6-(4-Acetylpiperazin-1-yl)hexyl]-1-[3,4-bis(trifluoromethyl)phenyl]-4-methyl-1H-pyrrole-2,5-dione 1-[3,4-Bis(trifluoromethyl)phenyl]-3-[6-[4-(cyclobutylcarbonyl)piperazin-1-yl]hexyl]-4-methyl-1H-pyrrole-2,5-dione 1-[3,4-Bis(trifluoromethyl)phenyl]-3-methyl-4-[6-[4-[(thien-2-yl)carbonyl]-piperazin-1-yl]hexyl]-1H-pyrrole-2,5-dione 1-[3,4-Bis(trifluoromethyl)phenyl]-3-[6-[4-[4-(dimethylamino)benzoyl]piperazin-1-yl]hexyl]-4-methyl-1H-pyrrole-2,5-dione 1-[3,4-Bis(trifluoromethyl)phenyl]-3-methyl-4-[6-[4-(methylsulfonyl)piperazin-1-yl]hexyl]-1H-pyrrole-2,5-dione 3-[6-[4-[(2,1,3-Benzothiadiazol-4-yl)sulfonyl]piperazin-1-yl]hexyl]-1-[3,4-bis(trifluoromethyl)phenyl]-4-methyl-1H-pyrrole-2,5-dione 1-[3-Fluoro-4-(trifluoromethyl)phenyl]-3-[6-[4-(2-methoxybenzoyl)piperazin-1-yl]hexyl]-4-methyl-1H-pyrrole-2,5-dione 3-[6-[4-(Cyclobutylcarbonyl)piperazin-1-yl]hexyl]-1-[3-fluoro-4-(trifluoromethyl)phenyl]-4-methyl-1H-pyrrole-2,5-dione 1-[3-Fluoro-4-(trifluoromethyl)phenyl]-3-methyl-4-[6-[4-(thien-2-yl)carbonyl]piperazin-1-yl]hexyl]-1H-pyrrole-2,5-dione 3-[6-[4-[4-(Dimethylamino)benzoyl]piperazin-1-yl]hexyl]-1-[3-fluoro-4-(trifluoromethyl)phenyl]-4-methyl-1H-pyrrole-2,5-dione 3-[6-[4-Acetylpiperazin-1-yl)hexyl]-1-[3-fluoro-4-(trifluoromethyl)phenyl]-4-methyl-1H-pyrrole-2,5-dione 1-[3-Fluoro-4-(trifluoromethyl)phenyl]-3-methyl-4-[6-[4-(methylsulfonyl)-piperazin-1-yl]hexyl]-1H-pyrrole-2,5-dione 3-[6-[4-[(2,1,3-Benzothiadiazol-4-yl)sulfonyl]piperazin-1-yl]hexyl]-1-[3-fluoro-4-(trifluoromethyl)phenyl]-4-methyl-1H-pyrrole-2,5-dione 3-[4-(4-Acetylpiperazin-1-yl)butyl]-1-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-4-methyl-1H-pyrrole-2,5-dione 1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-methyl-4-[4-[4-(1-oxopropyl)-piperazin-1-yl]butyl]-1H-pyrrole-2,5-dione 1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-[4-[4-[(2-methoxyethoxy)-acetyl]piperazin-1-yl]butyl]-4-methyl-1H-pyrrole-2,5-dione 1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-[4-[4-[[2-(2-methoxyethoxy)ethoxy]-acetyl]piperazin-1-yl]butyl]-4-methyl-1H-pyrrole-2,5-dione 1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-methyl-4-[4-[4-(methylsulfonyl)-piperazin-1-yl]butyl]-1H-pyrrole-2,5-dione 4-[4-[1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]butyl]-N-ethylpiperazine-1-carbothioamide 4-[4-[1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]butyl]-N-propylpiperazine-1-carbothioamide 4-[4-[1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]butyl]-N-(prop-2-enyl)piperazine-1-carbothioamide 3-[5-(4-Acetylpiperazin-1-yl)pentyl]-1-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-4-methyl-1H-pyrrole-2,5-dione 1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-methyl-4-[5-[4-(1-oxopropyl)-piperazin-1-yl]pentyl]-1H-pyrrole-2,5-dione 1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-[5-[4-[(2-methoxyethoxy)-acetyl]piperazin-1-yl]pentyl]-4-methyl-1H-pyrrole-2,5-dione 1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-[5-[4-[[2-(2-methoxyethoxy)-ethoxy]acetyl]piperazin-1-yl]pentyl]-4-methyl-1H-pyrrole-2,5-dione 1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-methyl-4-[5-[4-(methylsulfonyl)-piperazin-1-yl]pentyl]-1H-pyrrole-2,5-dione 3-[5-[4-(Cyclopropylsulfonyl)piperazin-1-yl]pentyl]-1-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-4-methyl-1H-pyrrole-2,5-dione 1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-[5-[4-[[2-[2-(2-methoxyethoxy)-ethoxy]ethyl]sulfonyl]piperazin-1-yl]pentyl]-4-methyl-1H-pyrrole-2,5-dione 4-[5-[1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]-N-ethylpiperazine-1-carbothioamide 4-[5-[1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]-N-propylpiperazine-1-carbothioamide 4-[5-[1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]pentyl]-N-(prop-2-enyl)piperazine-1-carbothioamide 1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-[6-[4-(2-methoxybenzoyl)piperazin-1-yl]hexyl]-4-methyl-1H-pyrrole-2,5-dione 3-[6-[4-(Cyclobutylcarbonyl)piperazin-1-yl]hexyl]-1-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-4-methyl-1H-pyrrole-2,5-dione 1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-methyl-4-[6-[4-[(thien-2-yl)carbonyl]piperazin-1-yl]hexyl]-1H-pyrrole-2,5-dione 1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-[6-[4-[4-(dimethylamino)-benzoyl]piperazin-1-yl]hexyl]-4-methyl-1H-pyrrole-2,5-dione 3-[6-(4-Acetylpiperazin-1-yl)hexyl]-1-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-4-methyl-1H-pyrrole-2,5-dione 4-[4-[1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N,N-dimethylpiperazine-1-sulfonamide 1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-methyl-4-[6-[4-(methylsulfonyl)-piperazin-1-yl]hexyl]-1H-pyrrole-2,5-dione 3-[6-[4-[(2,1,3-Benzothiadiazol-4-yl)sulfonyl]piperazin-1-yl]hexyl]-1-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-4-methyl-1H-pyrrole-2,5-dione 1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-3-[6-[4-(ethylsulfonyl)piperazin-1-yl]hexyl]-4-methyl-1H-pyrrole-2,5-dione 4-[6-[1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-ethylpiperazine-1-carbothioamide 4-[6-[1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-propylpiperazine-1-carbothioamide 4-[6-[1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(prop-2-enyl)piperazine-1-carbothioamide 4-[6-[1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(phenylmethyl)piperazine-1-carbothioamide 4-[6-[1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-[(4-methylphenyl)methyl]piperazine-1-carbothioamide N-[(4-Chlorophenyl)methyl]-4-[6-[1-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]piperazine-1-carbothioamide 4-[6-[1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-phenylpiperazine-1-carbothioamide 4-[6-[1-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-3-yl]hexyl]-N-(2,6-dimethylphenyl)piperazine-1-carbothioamide 3-[6-[4-(2-Methoxybenzoyl)piperazin-1-yl]hexyl]-4-methyl-1-(4-methyl-1-oxo-1H-2,3-benzoxazin-6-yl)-1H-pyrrole-2,5-dione 3-[6-[4-(Cyclobutylcarbonyl)piperazin-1-yl]hexyl]-4-methyl-1-(4-methyl-1-oxo-1H-2,3-benzoxazin-6-yl)-1H-pyrrole-2,5-dione 3-Methyl-1-(4-methyl-1-oxo-1H-2,3-benzoxazin-6-yl)-4-[6-[4-[(thien-2-yl)carbonyl]piperazin-1-yl]hexyl]-1H-pyrrole-2,5-dione 3-[6-[4-[4-(Dimethylamino)benzoyl]piperazin-1-yl]hexyl]-4-methyl-1-(4-methyl-1-oxo-1H-2,3-benzoxazin-6-yl)-1H-pyrrole-2,5-dione 3-[6-(4-Acetylpiperazin-1-yl)hexyl]-4-methyl-1-(4-methyl-1-oxo-1H-2,3-benzoxazin-6-yl)-1H-pyrrole-2,5-dione 3-Methyl-1-(4-methyl-1-oxo-1H-2,3-benzoxazin-6-yl)-4-[6-[4-(methylsulfonyl)-piperazin-1-yl]hexyl]-1H-pyrrole-2,5-dione 1-(2,3-Dihydro-1-oxo-1H-inden-5-yl)-3-[6-[4-(2-methoxybenzoyl)piperazin-1-yl]hexyl]-4-methyl-1H-pyrrole-2,5-dione 3-[6-[4-(Cyclobutylcarbonyl)piperazin-1-yl]hexyl]-1-(2,3-dihydro-1-oxo-1H-inden-5-yl)-4-methyl-1H-pyrrole-2,5-dione 1-(2,3-Dihydro-1-oxo-1H-inden-5-yl)-3-methyl-4-[6-[4-[(thien-2-yl)carbonyl]-piperazin-1-yl]hexyl]-1H-pyrrole-2,5-dione 1-(2,3-Dihydro-1-oxo-1H-inden-5-yl)-3-[6-[4-[4-(dimethylamino)benzoyl]-piperazin-1-yl]hexyl]-4-methyl-1H-pyrrole-2,5-dione 3-[6-(4-Acetylpiperazin-1-yl)hexyl]-1-(2,3-dihydro-1-oxo-1H-inden-5-yl)-4-methyl-1H-pyrrole-2,5-dione 1-(2,3-Dihydro-1-oxo-1H-inden-5-yl)-3-methyl-4-[6-[4-(methylsulfonyl)-piperazin-1-yl]hexyl]-1H-pyrrole-2,5-dione 3-[6-[4-[(2,1,3-Benzothiadiazol-4-yl)sulfonyl]piperazin-1-yl]hexyl]-1-(2,3-dihydro-1-oxo-1H-inden-5-yl)-4-methyl-1H-pyrrole-2,5-dione 4-[3-[2-(4-Acetylpiperazin-1-yl)ethyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[2-[4-(1-oxopropyl)piperazin-1-yl]ethyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-3-[2-[4-(2-methyl-1-oxopropyl)piperazin-1-yl]ethyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[2-[4-(1-oxobutyl)piperazin-1-yl]ethyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[2-[4-(Cyclopropylcarbonyl)piperazin-1-yl]ethyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[2-[4-(Cyclobutylcarbonyl)piperazin-1-yl]ethyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[2-[4-[(thien-2-yl)acetyl]piperazin-1-yl]ethyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[2-[4-[(thien-2-yl)carbonyl]piperazin-1-yl]ethyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[2-[4-[(pyridin-4-yl)carbonyl]piperazin-1-yl]ethyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-3-[2-[4-(methylsulfonyl)piperazin-1-yl]ethyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[2-[4-(Ethylsulfonyl)piperazin-1-yl]ethyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[2-[4-(propylsulfonyl)piperazin-1-yl]ethyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[2-[4-(phenylsulfonyl)piperazin-1-yl]ethyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[2-[4-[(4-Cyanophenyl)sulfonyl]piperazin-1-yl]ethyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[2-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]ethyl]-N-ethylpiperazine-1-carbothioamide 4-[2-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]ethyl]-N-propylpiperazine-1-carbothioamide 4-[2-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]ethyl]-N-(prop-2-enyl)piperazine-1-carbothioamide S-Methyl 4-[2-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]ethyl]piperazine-1-carbothioate S-Ethyl 4-[2-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]ethyl]piperazine-1-carbothioate 4-[3-[3-[4-(2-Methoxybenzoyl)piperazin-1-yl]propyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[3-(4-Acetylpiperazin-1-yl)propyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[3-[4-(1-oxopropyl)piperazin-1-yl]-propyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-3-[3-[4-(2-methyl-1-oxopropyl)piperazin-1-yl]propyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[3-[4-(1-oxobutyl)piperazin-1-yl]propyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[3-[4-(Cyclopropylcarbonyl)piperazin-1-yl]propyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[3-[4-(Cyclobutylcarbonyl)piperazin-1-yl]propyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[3-[4-[(thien-2-yl)acetyl]piperazin-1-yl]propyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[3-[4-[(thien-2-yl)carbonyl]piperazin-1-yl]propyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[3-[4-[(pyridin-4-yl)carbonyl]piperazin-1-yl]propyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[3-[4-(3-Methoxy-1-oxopropyl)piperazin-1-yl]propyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[3-[4-[(2-Methoxyethoxy)acetyl]piperazin-1-yl]propyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[3-[4-[[2-(2-Methoxyethoxy)ethoxy]acetyl]piperazin-1-yl]propyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-3-[3-[4-(methylsulfonyl)piperazin-1-yl]propyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[3-[4-(Ethylsulfonyl)piperazin-1-yl]propyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[3-[4-(propylsulfonyl)piperazin-1-yl]propyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[3-[4-(phenylsulfonyl)piperazin-1-yl]propyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[3-[4-[(4-Cyanophenyl)sulfonyl]piperazin-1-yl]propyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]propyl]-N-ethylpiperazine-1-carbothioamide 4-[3-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]propyl]-N-propylpiperazine-1-carbothioamide 4-[3-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]propyl]-N-(prop-2-enyl)piperazine-1-carbothioamide S-Methyl 4-[3-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]propyl]piperazine-1-carbothioate S-Ethyl 4-[3-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]propyl]piperazine-1-carbothioate 4-[3-[4-[4-(2-Methoxybenzoyl)piperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-(4-Acetylpiperazin-1-yl)butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[4-[4-(1-oxopropyl)piperazin-1-yl]butyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-3-[4-[4-(2-methyl-1-oxopropyl)piperazin-1-yl]butyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[4-[4-(1-oxobutyl)piperazin-1-yl]butyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(Cyclopropylcarbonyl)piperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(Cyclobutylcarbonyl)piperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[4-[4-[(thien-2-yl)acetyl]piperazin-1-yl]butyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(3-Methoxy-1-oxopropyl)piperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-[(2-Methoxyethoxy)acetyl]piperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-[[2-(2-Methoxyethoxy)ethoxy]acetyl]piperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-[(1,3-Dimethyl-1H-pyrazol-5-yl)carbonyl]piperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-[(Furan-3-yl)carbonyl]piperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-[(2,5-Dimethylfuran-3-yl)carbonyl]piperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-[(Isoxazol-5-yl)carbonyl]piperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-3-[4-[4-[(5-methylisoxazol-3-yl)carbonyl]piperazin-1-yl]butyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[4-[4-[(thien-3-yl)carbonyl]piperazin-1-yl]butyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-3-[4-[4-[(4-methyl-1,2,3-thiadiazol-4-yl)carbonyl]piperazin-1-yl]butyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-[(Furan-2-yl)carbonyl]piperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[4-[4-[(thien-2-yl)carbonyl]piperazin-1-yl]butyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[4-[4-[(pyridin-4-yl)carbonyl]piperazin-1-yl]butyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-3-[4-[4-(methylsulfonyl)piperazin-1-yl]butyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(Ethylsulfonyl)piperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[4-[4-(propylsulfonyl)piperazin-1-yl]butyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[4-[4-(phenylsulfonyl)piperazin-1-yl]butyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-[(4-Cyanophenyl)sulfonyl]piperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-3-[4-[4-[(1-methyl-1H-imidazol-4-yl)sulfonyl]piperazin-1-yl]butyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-[(3,5-Dimethylisoxazol-4-yl)sulfonyl]piperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]butyl]-N-ethylpiperazine-1-carbothioamide 4-[4-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]butyl]-N-propylpiperazine-1-carbothioamide 4-[4-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]butyl]-N-(prop-2-enyl)piperazine-1-carbothioamide S-Methyl 4-[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]butyl]piperazine-1-carbothioate S-Ethyl 4-[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]butyl]piperazine-1-carbothioate 4-[3-[5-(4-Acetylpiperazin-1-yl)pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[5-[4-[ 1-oxopropyl)piperazin-1-yl]pentyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-3-[5-[4-(2-methyl-1-oxopropyl)piperazin-1-yl]pentyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[5-[4-(1-oxobutyl)piperazin-1-yl]pentyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(Cyclopropylcarbonyl)piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(Cyclobutylcarbonyl)piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[5-[4-[(thien-2-yl)acetyl]piperazin-1-yl]pentyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(3-Methoxy-1-oxopropyl)piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[(2-Methoxyethoxy)acetyl]piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[[2-(2-Methoxyethoxy)ethoxy]acetyl]piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[(1,3-Dimethyl-1H-pyrazol-5-yl)carbonyl]piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[(Furan-3-yl)carbonyl]piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[(2,5-Dimethylfuran-3-yl)carbonyl]piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[(Isoxazol-5-yl)carbonyl]piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-3-[5-[4-[(5-methylisoxazol-3-yl)carbonyl]piperazin-1-yl]pentyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[5-[4-[(thien-3-yl)carbonyl]piperazin-1-yl]pentyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-3-[5-[4-[(4-methyl-1,2,3-thiadiazol-4-yl)carbonyl]piperazin-1-yl]pentyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[5-[4-[(thien-2-yl)carbonyl]piperazin-1-yl]pentyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[5-[4-[(pyridin-4-yl)carbonyl]piperazin-1-yl]pentyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-3-[5-[4-(methylsulfonyl)piperazin-1-yl]pentyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(Ethylsulfonyl)piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[5-[4-(propylsulfonyl)piperazin-1-yl]pentyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[5-[4-(phenylsulfonyl)piperazin-1-yl]pentyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[(4-Cyanophenyl)sulfonyl]piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[(2-Methoxyethyl)sulfonyl]piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[[2-(2-Methoxyethoxy)ethyl]sulfonyl]piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[[2-[2-(2-Methoxyethoxy)ethoxy]ethyl]sulfonyl]piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-3-[5-[4-[(1-methyl-1H-imidazol-4-yl)sulfonyl]piperazin-1-yl]pentyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[(3,5-Dimethylisoxazol-4-yl)sulfonyl]piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[5-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]pentyl]-N-ethylpiperazine-1-carbothioamide 4-[5-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]pentyl]-N-propylpiperazine-1-carbothioamide 4-[5-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]pentyl]-N-(prop-2-enyl)piperazine-1-carbothioamide S-Methyl 4-[5-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]pentyl]piperazine-1-carbothioate S-Ethyl 4-[5-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]pentyl]piperazine-1-carbothioate 4-[4,4-Dimethyl-3-[6-(4-methylpiperazin-1-yl)hexyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-3-[6-[4-(1-methylethyl)piperazin-1-yl]hexyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(2-Methoxybenzoyl)piperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-(4-Acetylpiperazin-1-yl)hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[6-[4-(1-oxopropyl)piperazin-1-yl]hexyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-3-[6-[4-(2-methyl-1-oxopropyl)piperazin-1-yl]hexyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[6-[4-(1-oxobutyl)piperazin-1-yl]hexyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(Cyclopropylcarbonyl)piperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(Cyclobutylcarbonyl)piperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(3-Methoxy-1-oxopropyl)piperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-[(2-Methoxyethoxy)acetyl]piperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-[[2-(2-Methoxyethoxy)ethoxy]acetyl]piperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[6-[4-[(thien-2-yl)acetyl]piperazin-1-yl]hexyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-[(Furan-2-yl)carbonyl]piperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[6-[4-[(thien-2-yl)carbonyl]piperazin-1-yl]hexyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[6-[4-[(pyridin-4-yl)carbonyl]piperazin-1-yl]hexyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-3-[6-[4-(methylsulfonyl)piperazin-1-yl]hexyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(Ethylsulfonyl)piperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[6-[4-(propylsulfonyl)piperazin-1-yl]hexyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[6-[4-(phenylsulfonyl)piperazin-1-yl]hexyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-[(4-Cyanophenyl)sulfonyl]piperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[6-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]-N-ethylpiperazine-1-carbothioamide 4-[6-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]-N-propylpiperazine-1-carbothioamide 4-[6-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]-N-(prop-2-enyl)piperazine-1-carbothioamide S-Methyl 4-[6-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]piperazine-1-carbothioate S-Ethyl 4-[6-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]piperazine-1-carbothioate 4-[4,4-Dimethyl-3-[7-(4-methylpiperazin-1-yl)heptyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[7-(4-Acetylpiperazin-1-yl)heptyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-3-[7-[4-(methylsulfonyl)piperazin-1-yl]heptyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-3-[8-[4-(2-methyl-1-oxopropyl)piperazin-1-yl]octyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[8-[4-(Cyclopropylcarbonyl)piperazin-1-yl]octyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[8-[4-(Cyclobutylcarbonyl)piperazin-1-yl]octyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[8-[4-[(thien-2-yl)carbonyl]piperazin-1-yl]octyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[8-[4-[(pyridin-4-yl)carbonyl]piperazin-1-yl]octyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-3-[8-[4-(methylsulfonyl)piperazin-1-yl]octyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-3-[8-[4-(propylsulfonyl)piperazin-1-yl]octyl]-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-3-[8-[4-[(1-methylethyl)sulfonyl]piperazin-1-yl]octyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[8-[4-[(2-Methoxyethyl)sulfonyl]piperazin-1-yl]octyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[8-[4-[(4-Cyanophenyl)sulfonyl]piperazin-1-yl]octyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[8-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]octyl]-N-ethylpiperazine-1-carbothioamide 4-[8-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]octyl]-N-(prop-2-enyl)piperazine-1-carbothioamide S-Methyl 4-[8-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]octyl]piperazine-1-carbothioate 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[3-[4-[(thien-2-yl)carbonyl]piperazin-1-yl]propyl]-2-thioxoimidazolidin-4-one 3-[1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-[3-[4-[4-(dimethylamino)-benzoyl]piperazin-1-yl]propyl]-5,5-dimethyl-2-thioxoimidazolidin-4-one N-[(4-Chlorophenyl)methyl]-4-[3-[3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]propyl]piperazine-1-carbothioamide S-Ethyl 4-[3-[3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]propyl]piperazine-1-carbothioate 4-[3-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]propyl]-N,N-diethylpiperazine-1-carboxylic acid amide 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[4-[4-[(thien-2-yl)carbonyl]piperazin-1-yl]butyl]-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-[4-[4-(2-methoxybenzoyl)piperazin-1-yl]butyl]-5,5-dimethyl-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-[4-[4-[4-(dimethylamino)benzoyl]piperazin-1-yl]butyl]-5,5-dimethyl-2-thioxoimidazolidin-4-one 1-[4-[4-[2,1,3-Benzothiadiazol-4-yl)sulfonyl]piperazin-1-yl]butyl]-3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-2-thioxoimidazolidin-4-one N-(2,6-Dichloropyridin-4-yl)-4-[4-[3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]butyl]piperazine-1-carboxylic acid amide S-Methyl 4-[4-[3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]butyl]piperazine-1-carbothioate S-Ethyl 4-[4-[3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]butyl]piperazine-1-carbothioate 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[5-[4-(2-methyl-1-oxopropyl)piperazin-1-yl]pentyl]-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[5-[4-[(thien-2-yl)acetyl]piperazin-1-yl]pentyl]-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[5-[4-[(thien-2-yl)carbonyl]piperazin-1-yl]pentyl]-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-[5-[4-ethylsulfonyl)piperazin-1-yl]pentyl]-5,5-dimethyl-2-thioxoimidazolidin-4-one 4-[[4-[5-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]pentyl]piperazin-1-yl]sulfonyl]benzonitrile S-Ethyl 4-[5-[3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]pentyl]piperazine-1-carbothioate 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-[6-[4-(2-methoxybenzoyl)piperazin-1-yl]hexyl]-5,5-dimethyl-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-[6-[4-[4-(dimethylamino)benzoyl]piperazin-1-yl]hexyl]-5,5-dimethyl-2-thioxoimidazolidin-4-one 3-[[4-[6-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]piperazin-1-yl]carbonyl]benzonitrile 1-[6-(4-Acetylpiperazin-1-yl)hexyl]-3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[6-[4-(1-oxopropyl)piperazin-1-yl]hexyl]-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[6-[4-(2-methyl-1-oxopropyl)piperazin-1-yl]hexyl]-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[6-[4-(1-oxobutyl)piperazin-1-yl]hexyl]-2-thioxoimidazolidin-4-one 1-[6-[4-(Cyclopropylcarbonyl)piperazin-1-yl]hexyl]-3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-2-thioxoimidazolidin-4-one 1-[6-[4-(Cyclobutylcarbonyl)piperazin-1-yl]hexyl]-3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[6-[4-[(pyridin-4-yl)carbonyl]piperazin-1-yl]hexyl]-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[6-[4-[(thien-2-yl)carbonyl]piperazin-1-yl]hexyl]-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[6-[4-[(thien-2-yl)acetyl]piperazin-1-yl]hexyl]-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[6-[4-(methylsulfonyl)piperazin-1-yl]hexyl]-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-[6-[4-(ethylsulfonyl)piperazin-1-yl]hexyl]-5,5-dimethyl-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[6-[4-(propylsulfonyl)piperazin-1-yl]hexyl]-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[6-[4-(phenylsulfonyl)piperazin-1-yl]hexyl]-2-thioxoimidazolidin-4-one 4-[[4-[6-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]piperazin-1-yl]sulfonyl]benzonitrile 1-[6-[4-[(2,1,3-Benzothiadiazol-4-yl)sulfonyl]piperazin-1-yl]hexyl]-3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-2-thioxoimidazolidin-4-one 4-[6-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]-N-[3-(methylsulfanyl)phenyl]piperazine-1-carboxylic acid amide 4-[6-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]-N-(3-fluorophenyl)piperazine-1-carboxylic acid amide 4-[6-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]-N-(4-fluorophenyl)piperazine-1-carboxylic acid amide 4-[6-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]-N-ethylpiperazine-1-carbothioamide 4-[6-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]-N-propylpiperazine-1-carbothioamide 4-[6-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]-N-(prop-2-enyl)piperazine-1-carbothioamide 4-[6-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]-N-phenylpiperazine-1-carbothioamide 4-[6-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]-N-(phenylmethyl)piperazine-1-carbothioamide S-Methyl 4-[6-[3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]piperazine-1-carbothioate S-Ethyl 4-[6-[3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]piperazine-1-carbothioate 4-[6-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]-N,N-diethylpiperazine-1-carboxylic acid amide 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-[7-[4-(2-methoxybenzoyl)piperazin-1-yl]heptyl]-5,5-dimethyl-2-thioxoimidazolidin-4-one 1-[7-(4-Acetylpiperazin-1-yl)heptyl]-3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[7-[4-(1-oxopropyl)piperazin-1-yl]heptyl]-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[7-[4-(2-methyl-1-oxopropyl)piperazin-1-yl]heptyl]-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[7-[4-(1-oxobutyl)piperazin-1-yl]heptyl]-2-thioxoimidazolidin-4-one 1-[7-[4-(Cyclopropylcarbonyl)piperazin-1-yl]heptyl]-3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-2-thioxoimidazolidin-4-one 1-[7-[4-(Cyclobutylcarbonyl)piperazin-1-yl]heptyl]-3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[7-[4-[(thien-2-yl)carbonyl]piperazin-1-yl]heptyl]-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[7-[4-[(thien-2-yl)acetyl]piperazin-1-yl]heptyl]-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[7-[4-(methylsulfonyl)piperazin-1-yl]heptyl]-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-[7-[4-(ethylsulfonyl)piperazin-1-yl]heptyl]-5,5-dimethyl-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[7-[4-(propylsulfonyl)piperazin-1-yl]heptyl]-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[7-[4-(phenylsulfonyl)piperazin-1-yl]heptyl]-2-thioxoimidazolidin-4-one 4-[7-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]heptyl]-N-ethylpiperazine-1-carbothioamide 4-[7-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]heptyl]-N-propylpiperazine-1-carbothioamide 4-[7-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]heptyl]-N-(prop-2-enyl)piperazine-1-carbothioamide S-Methyl 4-[7-[3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]heptyl]piperazine-1-carbothioate S-Ethyl 4-[7-[3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]heptyl]piperazine-1-carbothioate 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-[8-[4-(2-methoxybenzoyl)piperazin-1-yl]octyl]-5,5-dimethyl-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-[8-[4-[4-(dimethylamino)-benzoyl]piperazin-1-yl]octyl]-5,5-dimethyl-2-thioxoimidazolidin-4-one 1-[8-(4-Acetylpiperazin-1-yl)octyl]-3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[8-[4-(1-oxopropyl)piperazin-1-yl]octyl]-2-thioxoimidazolidin-4-one 1-[8-[4-(Cyclopropylcarbonyl)piperazin-1-yl]octyl]-3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-2-thioxoimidazolidin-4-one 1-[8-[4-(Cyclobutylcarbonyl)piperazin-1-yl]octyl]-3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[8-[4-[(thien-2-yl)carbonyl]piperazin-1-yl]octyl]-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[8-[4-[(thien-2-yl)acetyl]piperazin-1-yl]octyl]-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[8-[4-[(pyridin-4-yl)carbonyl]piperazin-1-yl]octyl]-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[8-[4-(methylsulfonyl)piperazin-1-yl]octyl]-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-1-[8-[4-(ethylsulfonyl)piperazin-1-yl]octyl]-5,5-dimethyl-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[8-[4-(propylsulfonyl)piperazin-1-yl]octyl]-2-thioxoimidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-2-thioxo-1-[8-[4-[(2,2,2-trifluoroethyl)sulfonyl]piperazin-1-yl]octyl]imidazolidin-4-one 3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-1-[8-[4-(phenylsulfonyl)piperazin-1-yl]octyl]-2-thioxoimidazolidin-4-one 4-[8-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]octyl]-N-[3-(methylsulfanyl)phenyl]piperazine-1-carboxylic acid amide 4-[8-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]octyl]-N-(3-fluorophenyl)piperazine-1-carboxylic acid amide 4-[8-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]octyl]-N-ethylpiperazine-1-carbothioamide 4-[8-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]octyl]-N-propylpiperazine-1-carbothioamide 4-[8-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]octyl]-N-(prop-2-enyl)piperazine-1-carbothioamide 4-[8-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]octyl]-N-(phenylmethyl)piperazine-1-carbothioamide 4-[8-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]octyl]-N-(phenyl-piperazine-1-carbothioamide S-Methyl 4-[8-[3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]octyl]piperazine-1-carbothioate S-Ethyl 4-[8-[3-(1,3-dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]octyl]piperazine-1-carbothioate 4-[8-[3-(1,3-Dihydro-1-oxoisobenzofuran-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]octyl]-N,N-diethylpiperazine-1-carboxylic acid amide 6-[4,4-Dimethyl-5-oxo-3-[5-[4-(methylsulfonyl)piperazin-1-yl]pentyl]-2-thioxoimidazolidin-1-yl]-4-methyl-1H-2,3-benzoxazin-1-one 6-[4,4-Dimethyl-5-oxo-3-[6-[4-(methylsulfonyl)piperazin-1-yl]hexyl]-2-thioxoimidazolidin-1-yl]-4-methyl-1H-2,3-benzoxazin-1-one 1-[6-(4-Acetylpiperazin-1-yl)hexyl]-3-(2,3-dihydro-1-oxo-1H-inden-5-yl)-5,5-dimethyl-2-thioxoimidazolidin-4-one 3-(2,3-Dihydro-1-oxo-1H-inden-5-yl)-5,5-dimethyl-1-[6-[4-(2-methyl-1-oxopropyl)piperazin-1-yl]hexyl]-2-thioxoimidazolidin-4-one 3-(2,3-Dihydro-1-oxo-1H-inden-5-yl)-5,5-dimethyl-1-[6-[4-[(thien-2-yl)carbonyl]piperazin-1-yl]hexyl]-2-thioxoimidazolidin-4-one 3-(2,3-Dihydro-1-oxo-1H-inden-5-yl)-5,5-dimethyl-1-[6-[4-[(pyridin-4-yl)carbonyl]piperazin-1-yl]hexyl]-2-thioxoimidazolidin-4-one 3-(2,3-Dihydro-1-oxo-1H-inden-5-yl)-5,5-dimethyl-1-[6-[4-(methylsulfonyl)piperazin-1-yl]hexyl]-2-thioxoimidazolidin-4-one 3-(2,3-Dihydro-1-oxo-1H-inden-5-yl)-5,5-dimethyl-1-[6-[4-(propylsulfonyl)piperazin-1-yl]hexyl]-2-thioxoimidazolidin-4-one 4-[6-[3-(2,3-Dihydro-1-oxo-1H-inden-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]-N-ethylpiperazine-1-carbothioamide S-Methyl 4-[6-[3-(2,3-dihydro-1-oxo-1H-inden-5-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]piperazine-1-carbothioate

9. Compounds according to claim 1, namely 4-[3-[3-[4-[(2-Methoxyethyl)sulfonyl]piperazin-1-yl]propyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]butyl]piperazine-1-carbonitrile rel-4-[3-[4-[(2R,5S)-4-Acetyl-2,5-dimethylpiperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-(4-Acetylhexahydro-1H-1,4-diazepin-1-yl)butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[3-[4-[(2R,5S)-2,5-Dimethyl-4-(2-methyl-1-oxopropyl)piperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(2-Hydroxy-2-methyl-1-oxopropyl)piperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(2,2-Dimethyl-1-oxopropyl)piperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[3-[4-[(2R,5S)-4-(2,2-Dimethyl-1-oxopropyl)-2,5-dimethylpiperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(2,2-Dimethyl-1-oxopropyl)hexahydro-1H-1,4-diazepin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[3-[4-[(2R,5S)-4-(Cyclopropylcarbonyl)-2,5-dimethylpiperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-(Methoxyacetyl)piperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[Hexahydro-4-(3-methoxy-1-oxopropyl)-1H-1,4-diazepin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-2-thioxo-3-[4-[4-(trifluoroacetyl)piperazine-1-butyl]imidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[Hexahydro-4-(trifluoroacetyl)-1H-1,4-diazepin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-[(Furan-2-yl)carbonyl]hexahydro-1H-1,4-diazepin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[Hexahydro-4-[(thien-2-yl)carbonyl]-1H-1,4-diazepin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[4,4-Dimethyl-3-[4-[(2R,5S)-2,5-dimethyl-4-(methylsulfonyl)piperazin-1-yl]butyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[Hexahydro-4-(methylsulfonyl)-1H-1,4-diazepin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[4-[4-[(2-Methoxyethyl)sulfonyl]piperazin-1-yl]butyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile S-Methyl 4-[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]butyl]hexahydro-1H-1,4-diazepine-1-carbothioate N,N-Dimethyl 4-[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]butyl]piperazine-1-sulfonamide 4-[3-[5-[4-(2-Methoxybenzoyl)piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[5-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]pentyl]piperazine-1-carbonitrile rel-4-[3-[5-[(2R,6S)-4-Acetyl-2,6-dimethylpiperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-(4-Acetylhexahydro-1H-1,4-diazepin-1-yl)pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[Hexahydro-4-(2-methyl-1-oxopropyl)-1H-1,4-diazepin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(2-Hydroxy-2-methyl-1-oxopropyl)piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(2,2-Dimethyl-1-oxopropyl)piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(2,2-Dimethyl-1-oxopropyl)hexahydro-1H-1,4-diazepin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-(Methoxyacetyl)piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-2-thioxo-3-[5-[4-(trifluoroacetyl)piperazin-1-yl]pentyl]imidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[(Furan-3-yl)carbonyl]hexahydro-1H-1,4-diazepin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[Hexahydro-4-[(thien-3-yl)carbonyl]-1H-1,4-diazepin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[4-[(Furan-2-yl)carbonyl]hexahydro-1H-1,4-diazepin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[Hexahydro-4-[(thien-2-yl)carbonyl]-1H-1,4-diazepin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[3-[5-[(2R,6S)-2,6-Dimethyl-4-(methylsulfonyl)piperazin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[5-[Hexahydro-4-(methylsulfonyl)-1H-1,4-diazepin-1-yl]pentyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile S-Methyl 4-[5-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]pentyl]hexahydro-1H-1,4-diazepine-1-carbothioate N,N-Dimethyl 4-[5-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]pentyl]piperazine-1-sulfonamide 4-[6-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]piperazine-1-carbonitrile rel-4-[3-[6-[(2R,5S)-4-Acetyl-2,5-dimethylpiperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[3-[6-[(2R,6S)-4-Acetyl-2,6-dimethylpiperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[3-[6-[(2R,5S)-2,5-Dimethyl-4-(2-methyl-1-oxopropyl)piperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[Hexahydro-4-(2-methyl-1-oxopropyl)-1H-1,4-diazepin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(2-Hydroxy-2-methyl-1-oxopropyl)piperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(2,2-Dimethyl-1-oxopropyl)piperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[3-[6-[(2R,5S)-4-(2,2-Dimethyl-1-oxopropyl)-2,5-dimethylpiperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[3-[6-[(2R,6S)-4-(2,2-Dimethyl-1-oxopropyl)-2,6-dimethylpiperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[3-[6-[(2R,5S)-4-(Cyclopropylcarbonyl)-2,5-dimethylpiperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-(Methoxyacetyl)piperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[3-[6-[(2R,5S)-4-(3-Methoxy-1-oxopropyl)-2,5-dimethylpiperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[Hexahydro-4-(3-methoxy-1-oxopropyl)-1H-1,4-diazepin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-2-thioxo-3-[6-[4-(trifluoroacetyl)piperazin-1-yl]hexyl]imidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[3-[6-[(2R,5S)-2,5-Dimethyl-4-(trifluoroacetyl)piperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[3-[6-[(2R,5S)-4-[(Furan-3-yl)carbonyl]-2,5-dimethylpiperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[3-[6-[(2R,5S)-4-[(Isoxazol-5-yl)carbonyl]-2,5-dimethylpiperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[3-[6-[(2R,5S)-4-[(Furan-2-yl)carbonyl]-2,5-dimethylpiperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-[(Furan-2-yl)carbonyl]hexahydro-1H-1,4-diazepin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[3-[6-[(2R,5S)-2,5-Dimethyl-4-[(thien-2-yl)carbonyl]piperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[Hexahydro-4-[(thien-2-yl)carbonyl]-1H-1,4-diazepin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[3-[6-[(2R,5S)-2,5-Dimethyl-4-(methylsulfonyl)piperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[3-[6-[(2R,6S)-2,6-Dimethyl-4-(methylsulfonyl)piperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[Hexahydro-4-(methylsulfonyl)-1H-1,4-diazepin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[3-[6-[(2R,5S)-4-(Ethylsulfonyl)-2,5-dimethylpiperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-3-[6-[4-[(1-methylethyl)sulfonyl]piperazin-1-yl]hexyl]-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[6-[4-[(2-Methoxyethyl)sulfonyl]piperazin-1-yl]hexyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile S-Methyl 4-[6-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]hexyl]hexahydro-1H-1,4-diazepine-1-carbothioate 4-[7-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]heptyl]piperazine-1-carbonitrile rel-4-[3-[7-[(2R,6S)-4-Acetyl-2,6-dimethylpiperazin-1-yl]heptyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[7-[4-(2-Hydroxy-2-methyl-1-oxopropyl)piperazin-1-yl]heptyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[7-[4-(2,2-Dimethyl-1-oxopropyl)piperazin-1-yl]heptyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[3-[7-[(2R,6S)-4-(2,2-Dimethyl-1-oxopropyl)-2,6-dimethylpiperazin-1-yl]heptyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[7-[4-(Methoxyacetyl)piperazin-1-yl]heptyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-2-thioxo-3-[7-[4-(trifluoroacetyl)piperazin-1-yl]heptyl]imidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[3-[7-[(2R,6S)-2,6-Dimethyl-4-(trifluoroacetyl)piperazin-1-yl]heptyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[3-[7-[(2R,6S)-2,6-Dimethyl-4-(methylsulfonyl)piperazin-1-yl]heptyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[7-[4-[(2-Methoxyethyl)sulfonyl]piperazin-1-yl]heptyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[8-[3-[4-Cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]octyl]piperazine-1-carbonitrile rel-4-[3-[8-[(2R,6S)-4-Acetyl-2,6-dimethylpiperazin-1-yl]octyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[8-[4-(2-Hydroxy-2-methyl-1-oxopropyl)piperazin-1-yl]octyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile rel-4-[3-[8-[(2R,6S)-4-(2,2-Dimethyl-1-oxopropyl)-2,6-dimethylpiperazin-1-yl]octyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[8-[4-(Methoxyacetyl)piperazin-1-yl]octyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-2-thioxo-3-[8-[4-(trifluoroacetyl)piperazin-1-yl]octyl]imidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[3-[8-[4-(Methoxyacetyl)piperazin-1-yl]octyl]-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 4-[4,4-Dimethyl-5-oxo-2-thioxo-3-[8-[4-(trifluoroacetyl)piperazin-1-yl]octyl]imidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile N,N-Dimethyl 4-[8-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]octyl]piperazine-1-sulfonamide

10. Process for the production of compounds of general formula I according to claim 1, wherein either a compound of general formula VIII 24in which A, B, n, i, j, R and R′ have the meaning that is indicated in general formula I in claim 1, is reacted with one of the reagents Z-N═O Z-N═S Z-COCl Z-SO2Cl ZO—COCl ZS—COCl ZZ′N—COCl in which Z and Z′ have the meaning that is indicated in claim 1, in the presence of a base, or a compound of the formula V—W—(CH2)n—I   VII is reacted with a product of the formula 25in which i, j, Y, Z, Z′, R and R′ have the meaning that is indicated in general formula I in claim 1, in the presence of a base and optionally then is converted into a pharmacologically compatible salt.

11. Intermediate products of general formula VIII

12. Intermediate products of general formula VIII

13. Intermediate products of general formula VII

14. Intermediate products of general formula VII

15. Pharmaceutical compositions that contain at least one compound of general formula I according to one of claims 1 to 9, together with pharmaceutically compatible adjuvants and vehicles.

16. Use of the compounds of general formula I according to one of claims 1 to 9 for the production of a pharmaceutical agent.

17. Use of the compounds of general formula I according to claim 16 for the production of a pharmaceutical agent for treating tumor diseases that can be influenced by the inhibition and/or destabilization of the androgen receptor.

18. Use according to claim 16 for the production of a pharmaceutical agent for treating prostate cancers.

19. Use according to claim 16 for the production of a pharmaceutical agent for treating benign prostate hyperplasia, androgenetic alopecia, hirsutism and androgen-dependent acne.