MXPA06009687A

MXPA06009687A - Piperazine urea derivatives for the treatment of endometriosis

Info

Publication number: MXPA06009687A
Application number: MXPA/A/2006/009687A
Authority: MX
Inventors: Horuk Richard; Kaufmann Ulrike
Original assignee: Horuk Richard; Kaufmann Ulrike; Schering Aktiengesellschaft
Priority date: 2004-02-24
Filing date: 2006-08-24
Publication date: 2007-04-10

Abstract

Use of a compound of the following formula (Ia) for the production of a medicament for the treatment of endometriosis in human wherein the treatment comprises administering to a human female in need of such treatment a therapeutically effective amount of said compound.

Description

PIPERAZINES DERIVED FROM UREA FOR THE TREATMENT OF ENDOMETROSIS FIELD OF THE INVENTION The present invention relates to piperazine derivatives and their pharmaceutically acceptable salts, which inhibit the activity of the chemokines, MlP-la and RANTES which are antagonists of Human Chemokine Receptor 1"CC" (CCR1) which in that way they are useful for the treatment of endometrosis, it also refers to pharmaceutical compositions containing the derivatives or their acceptable salts for pharmaceutical use, and to methods for their use Background of the invention Chemokine receptors are expressed in the leukocytes and process the signals that follow the chemokine binding, due to which said signals eventually transduce in the migration of the leukocytes towards the source of the chemokine or its activation, therefore, by regulating the migration and activation of leukocytes from peripheral blood to extravascular sites in organs, skin, joints or connective tissue, chemokines they play a critical role in maintaining host defenses as well as in the development of the immune response. It has been found that Human CC Chemotherapy Receptor 1 (CCR1) responds to several human CC chemokines in a variety of assays including calcium mobilization, inhibition of adenylate cyclase increase in extracellular acidification, and chemotaxis. of chemokines that can be designated by the CCR1 is broad and includes MIP-1 alpha, RANTES, MCP-3, etc. All said ligands are potent agonists for human CCR1 (EC50 <10nM). it is capable of binding to MIP-1B and human MCP-1 with low affinity (> 100nM) but neither of the two ligands is capable of signaling (1). ' Through the use of polyclonal antibodies to CCR1, it has been found that the receptor is expressed in monocytes and lymphocytes but not in neutrophils. '(2) It has been reported that molecules that inhibit CCR1 activity provide benefits to treat diseases such as example multiple sclerosis, rheumatoid arthritis and other chronic inflammatory diseases Endometrosis is a chronic inflammatory disease, characterized by the implantation and growth of endometrial tissue outside the uterine cavity (3) Classically described as the presence of endometrial tissue (glandular epithelium and stroma) outside the uterine cavity Endometrosis is a chronic benign disease that affects 15-20% of all women during their reproductive life.The symptoms of endometrosis are chronic pelvic pain, progressive dysmenorrhea, dyspareunia as well as infertility.The treatment of endometrosis includes surgical resection and / or m edication with hormonal agents such as gonadotropin-releasing hormone (GnRH) agonists and androgens. However, long-term medication with hormonal agents is undesirable due to side effects such as menopausal disorders (hot flashes), genital bleeding and bone demineralization. Frequently the clinical control of endometrosis is very difficult and the proportion of recurrence is high after discontinuing the medication. The role of CCR1 and its ligands in endometrosis arises from the fact that retrograde menstruation is postulated as the initiating event in the pathogenesis of the disease. In addition, it is accompanied by an intraperitoneal infiltration of macrophages and T cells in endometriotic lesions. The recruitment of such leukocytes within the endometrial lesions is initiated by the local production of chemokines. The most notable example of CC chemokine, RANTES (3-7), is, among others, a ligand for the chemokine receptors CCR1, and CCR5. The expression of RANTES is sensitized in endometriotic lesions and peritoneal fluid from patients with endometrosis. In comparison with other chemokines, RANTES plays an important role in the pathogenesis of endometrosis. Related Works Piperazine derivatives of the type similar to the compounds of the invention are known in the literature as useful for a variety of pharmaceutical indications, in particular as cardiotonic, neurotropic or anti-inflammatory agents. For example, published European patent application 0 702 010 (Adir) describes certain piperazine derivatives as useful as depressants of the central nervous system and in the treatment of Alzheimer's disease and other diseases of immunological origin, such as arthritis. and intestinal peristalsis. The published European patent application 0 655 442 (Fujisawa) discloses similar piperazine derivatives as tachykinin antagonists which are useful for treating inflammatory diseases such as for example rheumatoid arthritis and osteoarthritis. A Czech published patent application, 260089, and '5 a related article, Valenta, V. Et al. , Collection Chem. Commun. (1987), Vol. 52, pp. 3013-3023, discloses piperazine derivatives as potential neurotropic and cardiovascular agents. The published European patent application 0 252 422 (Mitsubishi) and the published German patent application 3614363 (Hoechst) disclose piperazine derivatives which are useful as cardiotonic agents. The published European patent application 0 190 685 (GD Searle) describes piperazine derivatives that block the metabolic pathway of 5-lipoxygenase from the ara-1.5-quidonic acid cascade, and are therefore useful in the treatment of allergic reactions and of hypersensitivity and inflammation. The published PCT patent application, WO 96/34864 (Schering Plow) discloses piperazine derivatives useful as neurokinin antagonists. The published European patent application 1 254 899 (Schering AG) discloses the piperazine derivatives included in the present application for the treatment of an inflammatory disorder.

PCT patent application WO 02/36581 (Schering AG) also discloses piperazine derivatives included in the present application for the diagnosis of Alzheimer's disease. All the above references are incorporated herein in their entirety as a reference. None of the above references describes the piperazine derivatives included in the present application for the treatment of endometrosis in women, wherein said piperazine derivatives are antagonists of Human C-C Receptor 1 (CCR1). SUMMARY OF THE INVENTION This invention relates to the use of a compound of the following formula (a) or its pharmaceutically acceptable salt for the treatment and prevention of endometrosis in humans wherein the treatment comprises administering to a human of sex female which needs said treatment an effective amount in therapeutic terms of said compound. Accordingly, in one aspect, this invention provides compounds of the following formula (la): (the) where: one or more substituents selected independently from the group consisting of oxo, halo, alkyl, cycloalkyl, cycloalkylalkyl, cycloalkylaminoalkyl, (cycloalkylalkyl) aminoalkyl, haloalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, formyl, formylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy) aralkyl, (hydroxy) cycloalkylalkyl, mercaptoalkyl, cyanoalkyl, haloalquilcarbonilaminoalquilo, (alkoxy) aralkyl, alkoxyalkyl, aryloxyalkyl, coxialquilo aralkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkylthioalkyl, aminoalkyl monoalkylaminoalkyl chyle, dialkylaminoalkyl, mo- noarilaminoalquilo, monoaralquilaminoalquilo, bonilaminoalquilo alquilcar-, (alkylcarbonyl) (alkyl) aminoalkyl, azidoalkyl, ureidoalkyl, monoalquilureidoalquilo, dialquilureidoalquilo, (alkoxycarbonylalkyl) ureidoalkyl, alkoxycarbonylaminoalkyl, chyle hidroxialquilaminoal-, ariloxialquilcarboniloxial chyle, boniloxialquilo alcoxialquilcar-, aralcoxialquilcarboniloxialquilo, alkylcarbonyl, alkylcarbonylalkyl, carboxy, alkoxy carbonyl, aralkoxycarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, monoarilaminocarbonilo, monoaralquilaminocarboni- it, carboxyalkyl, alkoxycarbonylalkyl, - aralcoxicar- bonilalquilo, aminocarbonyl, monoalquilaminocar- bonilalquilo, dialkylaminocarbonylalkyl ,. monoarylaminocarbonyl alkyl, monoaralkylaminocarbonylalkyl, arylsulphonyl, heterocyclyl and heterocyclylalkyl; R2 is one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, chyle alquilsulfonilal-, alkoxy, aryloxy, haloalkyl, formyl , formylalkyl, Nitro, nitroso, cyano, aralkoxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy) cycloalkylalkyl, cycloalkylamino, cicloalquilaminoalqui- it, (cycloalkylalkyl) amino, (cicloalquialquil) AMI- alkylaminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy) aralkyl, hyaroxyalkylthioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy) aralkyl, aryloxyalkyl, aralkoxyalkyl, amino, monoalkylamino, dialkylamino, onoarylamino, monoaralkylamino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, hydroxyalkylaminoalkyl, monoarylaminoalkyl, monoalkylalkyalkyl alkylcarbonylamino, (alquilcarbo- nil) (alkyl) amino, alkylcarbonylaminoalkyl, (alkyl- carbonyl) (alkyl) aminoalkyl, alkoxycarbonylamino, (alkoxycarbonyl) (alkyl) amino, alcoxicarbonilaminoalqui- it, (alkoxycarbonyl) (alkyl) aminoalkyl, carboxy, to - coxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, alkylcarbonylalkyl, a rilcarbonilo, arylcarbonylalkyl, aralkylcarbonyl, aralquilcarbonilalquilo, chyle carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alcoxialquilcarboniloxialquilo, aminocarbonyl, monoal- quilaminocarbonilo, dialkylaminocarbonyl, monoarilami- nocarbonilo, monoaralquilaminocarbonilo, amino-carbonyl, monoalkylaminocarbonylalkyl, dialkylamino- carbonyl, monoarilaminocarbonilalquilo, monoaral- quilaminocarbonilalquilo, amidino, guanidino, ureido, monoalquilureido, dialkylureido, ureidoalkyl, monoal- quilureidoalquilo, dialquilureidoalquilo, and heterocyclylalkyl; R3 is a carbocyclic ring system substituted by one or more substituents selected independently from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, hydroxyalkoxy, aryloxy, haloalkyl, formyl, forylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, aminoalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy) cycloalkylalkyl, cycloalkylamino, cycloalkylaminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy) aralkyl, (monoalkylamino) aralkyl, (hydroxyalkyl) hyalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy) aralkyl, aryloxyalkyl, aral-coxyalkyl, amino, monoalkylamino, dialkylamino, o-noarylamino, monoaralkylamino, aminoalkylamino, hete-rociclilamino, (cycloalkylalkyl) amino, al alkylcarbonylamino, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbamylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbonyl) (alkyl) amino, (alkoxycarbonyl) (alkyl) amino, alkylsulfonylamino, aminoalkyl, monoalkylaminoalkyl dialkylaminoalkyl, hydroxyalkylaminoalkyl, monoalkylaminoalkyl, monoaralkylaminoalkyl, alkylcarbonylaminoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl) (alkyl) aminoalkyl, (cycloalkyalkyl) aminoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylalkylcarbonylaminoalkyl, (alkoxycarbonyl) (alkyl) aminoalkyl, alkylsulfonylaminoalkyl, ( alkylsulfonyl) (alkyl) aminoalkyl, arylsulfonylamine-noalkyl, (arylsulfonyl) (alkyl) aminoalkyl, heterocyclylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, (hydroxyalkoxy) carbonyl, carboxyalkyl, coxicarbonilalquilo, aralkoxycarbonylalkyl, alcoxialquilcar-boniloxialquilo, dialquilaminocarboniloxialquilo, alkylcarbonylalkyl, arylcarbonylalkyl, aralquilcarbo-nilalquilo, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, monoarilaminocarbonilo, Monoa-ralquilaminocarbonilo, (aminocarbonyl) aminocarbonyl, (monoalquilaminocarbonilalquil) aminocarbonyl, (carboxyalkyl) aminocarbonyl, (alcoxicarbonilal- quil) aminocarbonyl, (aminoalkyl) aminocarbonyl, (hydroxyalkyl) aminocarbonyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylaminocarbonylalkyl, monoaralkylaminocarbonylalkyl, amidino, hydroxyamidino, guanidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, monohaloalkylureido, (monoalkyl) ) (ono-aryl) ureido, dialkylureide, diarylureido, (haloalkylcarbonyl) ureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoalkarylureturide alkyl, monohaloalkylureidoalkyl, (haloalkyl) (alkyl) ureidoalkyl, (alkoxycarbonylalkyl) ureidoalkyl, glycinamide, monoalkylglycinamido, aminocarbonylglycinamido, (alkoxyalkylcarbonyl) glycinamide, (aminocarbonyl) (alkyl) glycinamide, (alkoxycarbonylalkylcarbonyl) (alkyl) glycinamide, (alkoxycarbonyllaminocarbonyl) glycinamide. arylcarbonylglycine-mido, (arylcarbonyl) (alkyl) glycinamide, (monoaralkyl-aminocarbonyl) glycinamide, (monoaralkylaminocarbo-nil) (alkyl) glycolinamide, (monoarylaminocarbonyl) glycinamide, (monoarylaminocarbonyl) (alkyl) glycinamide, glycinamidoalkyl, alaninamide, monoalkylalaninamide, alanine idoalkyl, heterocyclyl and heterocyclylalkyl; 3 is a heterocyclic ring system substituted by one or more substituents selected independently from the group consisting of hydrogen, hydroxy, halo, alkyl, alkylsufonyl, arylsulfonyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, haloalkoxy, alkenyl, alkynyl, aryl, aralkyl, amino, monoalkylamino, dialkylamino, monoarylamino, monoaralkylamino, alkylcarbonylamino, alkoxycarbonylamino, alkenylcarbonyl, cycloalkylcarbonylamino, arylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbo-nil) (alkyl) amino, (alkoxycarbonyl) (alkyl) amino, alkylsulfonylamino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, alkylcarbonylaminoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl) (alkyl) aminoalkyl, alkoxycarbonylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcafbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, monoarylaminocarbonyl, aminocarbonylalkyl, onoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylaminocarbonylalkyl, guanidino, ureido, monoalkylureido, ureidoalkyl, monoalkylureidoalkyl, and glycinamide; is -O-, -N (R7) -, - C (R8) 2- or a bond; R5 is an alkylene chain or an alkylidene chain, or, if R4 is a bond, R5 is an alkylidene chain which is optionally substituted by aryl or -N (R7) 2; or R4 and R5 together are a -CH = CH-R6 is -C (0) -, - C (S) -, -CH2- or a bond; each R7 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralquilcarbonilalquilo, aminocarbonyl, onoalquilami- nocarbonilo, dialkylaminocarbonyl, and alkoxycarbonyl; and each R8 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, hydroxy, alkoxy, hydroxyalkyl, alkoxyalkyl, amino, monoalqui- lamino, dialkylamino, alkylcarbonylamino, alkoxycarbonylamino cycloalkyl-, cicloalquilalquilcarbonilamino, alkoxycarbonylamino, alkylsulfonylamino, arylcarbonylamino , alkoxycarbonylalkylcarbonylamino ,. (Alkylcarbonyl) (alkyl) amino, aralquilcarbonilaird.no, (aralquilcarbo- nil) (alkyl) amino, alkylcarbonylaminoalkyl, cycloalkylene inoalquilo quilcarbonila, alkoxycarbonylaminoalkyl, (alkylcarbonyl) (alkyl) aminoalkyl, minoalquilo aralquilcarbonila-, heterocyclylcarbonylaminoalkyl, (aralkyl quilcarbonil) (alkyl) aminoalkyl, arylsulfonylamino, alkylsulfonylaminoalkyl, ureido, monoalquilureido, monohaloalquiiureido, dialkylureido, ureidoalkyl, noalquilureidoalquilo mo-, dialquilureidoalquilo, monoha- loalquilureidoalquilo, aminoalkyl, monoalquilaminoal- chyle, dialkylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonyl, monoalquilaminocar- bonilalquilo, and dialkylaminocarbonylalkyl; with the proviso that when R4 is -N (R7) -, R3 can not be a 4-8 membered heterocyclic ring system consisting of carbon atoms and only one nitrogen atom; and with the proviso that when R 4 is -C (R 8) 2 or a bond, R 3 can not be a saturated 4- to 6-membered saturated heterocyclic ring system consisting of carbon atoms and two nitrogen atoms, and as the sole stereoisomer or a mixture thereof; or an acceptable salt for pharmaceutical use thereof. The proviso is intended to exclude the compounds disclosed in the art document. Patent application WO2004 / 037796 in its entirety is incorporated by reference to the present application. Some advantageous embodiments according to the present invention are the compound according to general formula I, II, IIa and III as defined in WO2004 / 037796 for the production of a medicament for the treatment and prevention of endometriosis. Some particularly favorable embodiments of the present invention are the following compounds as reported in WO2004 / 037796: (5-Chloro-2- [(E) -3- [(R) -4- (4-fluorobenzyl) -2 -metilpiperazin- 1-yl] -3-oxopropenyl] - phenyl) -urea, N- (5-Chloro-2- [(E) -3- [(R) -4- (4-fluorobenzyl) -2-metilpipe - razin-1-yl] -3-oxo-propenyl] phenyl) -methanesulfonamide, (5-Chloro-2- [(E) -3- [(2R, 5S) -4- (4-fluorobenzyl) -2,5-dimethylpiperazin-1-yl] -3-oxo-propenyl] -phenyl) - urea, N- (5-Chloro-2- [(E) -3- [(2R, 5S) -4- (4-fluorobenzyl) -2,5- dimethylpiperazin-1-yl] -3-oxo-propenyl] -phenyl ) - methanesulfonamide, (5-Chloro-2 { (E) -3- [4- (4-fluoro-benzyl) -2-methyl-piperazin-1-yl] -3-oxo-propenyl acid methyl ester .}. - phenyl) -acetic, 5-chloro-2- acid. { (E) -3- [(R) -4- (4-Fluoro-benzyl) -2-methyl-piperazin-1-yl] -3-oxo-propenyl} - benzoic, (5-chloro-2- { (E) -3- [(R) -4- (4-fluoro-benzyl) -2-methyl-piperazin-1-yl] -3-oxo-propenyl 4-methoxy-phenyl) -urea, (5-Chloro-2 { (E) -3- [(R) -4- (4-fluoro-benzyl) -2-methyl-pipera- zin-1-yl] -3-oxo-propenyl} -4-trifluoromethoxy-phenyl) -urea, 5-Chloro-2-. { (E) -3- [(R) -4- (4-Fluoro-benzyl) -2-methyl-piperazin-1-yl] -3-oX-propenyl} -4-methoxy-benzoic acid methyl ester. The patent application WO03 / 035627 in its entirety are incorporated by reference to the present application. Some advantageous embodiments according to the present invention are the compounds under general formula 1 as defined in claim 1 of WO03 / 035627 for the treatment and prevention of endometrosis. Some particularly favorable embodiments of the present invention are the following compounds as reported in WO03 / 035627: acid (5-Chloro-2-. {2- [4- (4-fluoro-benzyl) - (2R) -2- methyl-pipe-razin-1-yl] -2-oxo-ethoxy.} - phenyl) -acetic acid (5-Bromo-2- { 2- [4- (4-fluoro-benzyl) - ( 2R, 5S) -2,5-dimethyl-piperazin-1-yl] -2-oxo-ethoxy.} - phenyl) -acetic acid (5-Bromo-2- { 2- [4- (4-fluoro-benzyl) - (2R) -2-methyl-piperazin-1-yl] -2-oxo-ethoxy.} - phenyl) -acetic, 3- (5-Clsro-2- {2- [4- (4-Fluoro-benzyl) - (2R) -2-methyl-piperazin-1-yl] -2-oxo-ethoxy}. Phenyl) -propionic acid (5-chloro- 2- {2- [4- (3,4-difluoro-benzyl) - (2R, 5S) -2,5- dimethyl-piperazin-1-yl] -2-oxo-ethoxy} -phenyl) - acetic acid (5-Chloro-2- { 2- [4- (4-chloro-benzyl) - (2R, 5S) -2,5- dimethyl-piperazin-1-yl] -2-oxo- ethoxy.}. phenyl) -acetic acid, "(5-Chloro-2-. {2- [(2R) -2-ethyl-4- (4-fluoro-benzyl) -piperazin-1-yl]] - 2-Oxo-ethoxy.}.-Phenyl) -acetic acid (5-B) 2- (2R) -2-ethyl-4- (4-fluoro-benzyl) -piperazin-1-yl] -2-oxo-ethoxy} phenyl) - acetic, acid (5-Chloro-2- { 2- [4- (4-chloro-benzyl) - (2R) -2-methyl-piperazin-1-yl] -2-oxo-ethoxy .}.-phenyl) -acetic acid (5-Chloro-2- { 2- [4- (3,4-difluoro-benzyl) - (2R) -2-methyl-piperazin-1-yl] - 2-oxo-ethoxy.} - phenyl) -acetic acid, 3 ~ (5-Chloro-2- { 2- [4- (4-fluoro-benzyl) - (2R, 5S) ~ 2.5- dimethyl-piperazin-1-yl] -2-oxo-ethoxy.} - phenyl) -acrylic, N - [(5-chloro-2- { 2- [4- (4-fluoro-benzyl) - ( 2R, 5S) -2,5-dimethyl-piperazin-1-yl] -2-oxo-ethoxy.} - phenyl) -acetyl] -methanesulfonamide, N- (5-Chloro-2-. {2- 2- [ 4- (4-fluoro-benzyl) - (2R, 5S) -2,5-dimethyl-piperazin-1-yl] -2-oxo-ethoxy}. -benzoyl) -methanesulfonamide, N- [(5-chloro -2- { 2- [4 ~ (4-fluoro-benzyl) - (2R, 5S) -2,5- dimethyl-piperazin-1-yl] -2-oxo-ethoxy.} - phenyl) - acetyl] - C, C, C-trifluoro-methanesulfonamide, (5-Chloro-2- { 2- [4- (4-fluoro-benzyl) - (2R, 5S) -2,5-dimethyl-acid -piperazin-1-yl] -2-oxo-ethoxy.} - phenyl) -oxo-acetic acid (5-Chloro-2- { 2- [4- (4-fluoro-benzyl) - (2R , 5S) -2, 5-dimethyl-piperazin-1-yl] -2-oxo-ethoxy} -phenoxy) -acetic acid, 2- (5-Chloro-2- { 2- [4- (4-fluoro-benzyl) - (2R, 5S) -2,5- dimethyl-piperazin-1-yl- 2-oxo-ethoxy.]. -phenoxy) -2-methyl-propionic acid, (5-Chloro-2- { 2- [4- (4-fluoro-benzyl) - (2R, 5S) -2, 5-dimethyl-piperazin-1-yl] -2-oxo-ethoxy.]. -phenoxy) -difluoroacetic acid (5-chloro-2- { 2- [4- (4-fluoro-benzyl) - (2R) -2-methyl-piperazin-1-yl] -2-oxo-ethoxy.} - phenyl) -methanesulfonamide Patent application WO01 / 72728 in its entirety is incorporated by reference to the present application. Some advantageous embodiments according to the present invention are the compounds under general formula 1 as defined on page 2 of WO01 / 72728 as published for the treatment and prevention of endometrosis. Some particularly favorable embodiments of the present invention are the following compounds as reported in WO01 / 72728: N- [5-chloro-2- [2- [(2R, 5S) -4- [(4-fluorophenyl) methyl] - 2,5-dimethylpiperazinyl] -2-oxoethoxy] phenyltrifluoromethanesulfonamide, 5-chloro-2- [2- [(2R, 5S) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2 -oxoethoxy] -benzenesulfonamide. The patent application WO02 / 102787 in its entirety are incorporated by reference to the present application. Some Advantageous embodiments according to the present invention are the compounds of the formula I-WO02 / 102787 (I-WO02 / 102787) or their pharmaceutically acceptable salts and prodrugs; where a = 0, 1, 2, 3, 4 or 5; b = 0, 1 or 2; c = 0, 1 or 2; d = 0, 1.2, 3 or 4; X is -O-, -S-, -CH2- or -NR6- Y is (C6-C10) aryl, or (C2-C9) heteroaryl, each RI is independently selected from the group consisting of: H-, HO-, halo-, (C1-C8) alkyl- optionally substituted with 1-3 fluorine atoms, (C1-C8) alkyl-O- wherein the alkyl group is optionally substituted with 1-3 fluorine atoms, H0- (C1-C8) alkyl-, NC-, H2N-, H2N- (C1-C8) alkyl-, HO- (C = 0) -, (C1-C8) alkyl- (C = 0) -, (C1- C8) alkyl- (C = 0) - (C1-C8) alkyl-, H2N- (C = 0) -, H2 (C = 0) - (C1-C8) alkyl-; each R2 and R3 is independently selected from the group consisting of: H-, oxo, (C1-C8) alkyl- optionally substituted with 1-3 fluorine atoms, (C1-C8) alkyl-, (C6- C10) aryl-, (C6-C10) aryl- (C1-C8) alkyl-, H0- (C1-C8) alkyl-, (C1-C8) alkyl-O- (C1-C8) alkyl, H2N- (C1 -C8) alkyl, (C1-C8) alkyl-NH- (C1-C8) alkyl-, [(Cl-C8) alkyl] 2N- (C1-C8) alkyl-, (C2-C9) heterocyclyl- (Cl-) C8) alkyl, (C1-C8) alkyl- (C = 0) -NH- (C1-C8) alkyl-, (Cl-C8) alkyl-O- (C = 0) -NH- (C1-C8) alkyl , H2N- (C = 0NH- (Cl-C8) alkyl, (C1-C8) alkyl-S02-NH - '(Cl-C8) alkyl, (C2-C9) heteroaryl- (C1-C8) alkyl, H2N- (C = 0) -, H2N- (C = 0) - (CI-C8) alkylate, each R4 is independently selected from the group consisting of: H-, HO-, halo-, - NC-, HO- (C = 0-, H2N-, (C1-C8) alkyl-NH-, [(C1-C8) alkyl] 2N-, (C1-C8) alkyl-optionally substituted with 1-3 fluorine atoms, (Cl-) C8) alkyl-O- wherein the alkyl group is optionally substituted with 1-3 fluorine atoms, H0- (C1-C8) alkyl-, (C1-C8) alkyl-O- (C1-C8) alkyl-, H2N- (Cl- C8) alkyl-, (C1-C8) alkyl NH- (C1-C8) alkyl-, [(Cl- C8) alkyl ] 2N- (C1-C8) alkyl-, (C1-C8) alkyl- (C = 0) -, (Cl- C8) alkyl- (C = 0) - (CC8) alkyl-, (C6-C10) aryl -, (C2-Cg) heteroaryl-, (C6-C10) aryloxy, H2N- (C = 0), H2N- (C = 0) - (CC8) alkyl, (C1-C8) alkyl-NH- (C = 0) -, (C1-C8) alkyl- NH- (C = 0) - (C1-C8) alkyl-, [(C1-C8) alkyl] 2N (C = 0) -, [(C1-C8) alkyl ] 2-N- (C = 0) - (C1-C8) alkyl-, (C3-C8) cycloalkyl-, (C1-C8) alkyl-S02-, NC- (C8) alkyl-, (C1-C8) ) alkyl- (C = 0) -NH-, H2N- (C = 0) -NH-, H2N- (C = 0) -NH- (C1-C8) alkyl-; R5 is (C1-C8) alkyl-. for the treatment and prevention of endometrosis. Some particularly favorable embodiments of the present invention are the following compounds as reported in WO01 / 72728: acid (5-Chloro-2- { 2- [4- (4-fluoro-benzyl) - (2R, 5S) - 2,5-dimethyl-piperazin-1-yl] -2-oxo-ethoxy.} - phenyl) -methanesulfonic acid, (5-Chloro-2-. {2- [4- (4-fluoro- benzyl) - (2R) -2- e-tyl-piperazin-1-yl] -2-oxo-ethoxy.} - phenyl) -methanesulfonic acid (5-Bromo-2- { 2- [4- (4-fluoro-benzyl) - (2R, 5S) -2,5-dimethyl-piperazin-1-yl] -2-oxo-ethoxy.} - phenyl) -methanesulfonic acid (5- Bromo-2) - { 2- [4- (4-Fluoro-benzyl) - (2R) -2-methyl-piperazin-1-yl] -2-oxo-ethoxy.} -phenyl) -methanesulfonic acid (5- Chloro-2- {2- [4- (4-fluoro-benzyl) - (2R, 5S) -2,5-dimethyl-piperazin-1-yl] -2-oxo-ethoxy} - phenyl) - - ethanesulfonic, | Patent application WO2004 / 055031 in its entirety is incorporated by reference to the present application. Some advantageous embodiments according to the present invention are the compounds of the formula I - WO2004 / 055031 (I-WO2004 / 055031) or a prodrug thereof, or an acceptable salt for pharmaceutical use of the compound or its prodrug; where a = 0, 1, 2, 3, 4 or 5; b = 0, 1 or 2; c = 0, 1 or 2; d = 0, 1,2, 3 or 4; X is O, S, CH2 or NR6; Y is (C6-C10) aryl or (C2-C9) heteroaryl; each R1 is independently: hydroxy, halo, (Cl- C8) alkyl optionally substituted with 1 to 3 fluorine atoms, (C1-C8) alkoxy optionally substituted with 1-3 fluorine atoms, H0 (C1-C8) alkyl-, cyano, amino, H2N (C1-C8) alkyl-, carboxy, acyl, (C1-C8) alkyl (C = 0) (C1-C8) alkyl-, H2N (C = 0) -, or H2N (C = 0) (C1-C8) alkyl-; each R2 and R3 are independently: oxo, (C1-C8) alkyl optionally substituted with 1-3 fluorine atoms, (C3-C8) cycloalkyl-, (C3-C8) cycloalkyl- (C1-C8) alkyl-, (C6-C10) aryl-, (C6-C10) aryl (Cl- C8) alkyl-, H0 (C1-C8) alkyl-, (C1-C8) alkyl-O- (Cl- C8) alkyl-, H2N ( C1-C8) alkyl-, (C1-C8) alkyl-NH- (C1-C8) alkyl-, [(C1-C8) alkyl] 2N- (C1-C8) alkyl-, (C2-C9) heterocyclyl (C1 -C8) alkyl-, (C1-C8) alkyl (C = 0) NH (Ci-C8) alkyl-, (C1-C8) alkyl-O- (C = 0) NH (C1-C8) alkyl-, H2N (C = 0) NH (C1-C8) alkyl-, (Cl-C8) alkyl-S02-NH (C1-C8) alkyl-, (C2- C9) heteroaryl (C1-C8) alkyl-, H2N (C = 0), or H2N (C = 0) (Cl- C8) alkyl-; each R4 is independently: H0-, halo-, NC-, HO (C = 0) -, H2N-, (C1-C8) alkyl NH-, [(C1-C8) alkyl] 2N-, (Ci-) C8) alkyl-, optionally substituted with 1-3 fluorine atoms, (C1-C8) alkoxy optionally substituted with 1-3 fluorine atoms, HO (C1-C8) alkyl-, (C1-C8) alkyl-O- ( C1-C8) alkyl-, H2N (C1-C8) alkyl-, (C1-C8) alkylNH (C1-C8) alkyl-, [(Cl- C8) alkyl] 2N (Cl- C8) alkyl-, (C1- C8) alkyl (C = 0) - (C1-C8) alkyl (C = 0) (C1-C8) alkyl-, (C6-C10) aryl-, (C2-Cg) heteroaryl-, (C6-C10) aryloxy -, H2N (C = 0) -, H2N (C = 0) (CÍ-C8) alkyl-, (C1-C8) alkylNH (C = 0) -, (C1-C8) alkyl-NH (C = 0) (C1-C8) alkyl-, [(Cl-C8) alkyl] 2N (C = 0) -, [(C1-C8) alkyl] 2N (C = 0) (C1-C8) alkyl-, (C3) -C8) cycloalkyl-, (C1-C8) alkylS02-, NC (C1-C8) -alkyl (C = 0) NH-, H2N (C = 0) NH- or H2N (C = 0) NH- (C1-) C8) -alkyl-; R5 is attached to (C1-C8) -alkyl-; R6 is independently: hydroxy, amine or (C1-C8) -alkyl-NH; and R7 is independently: hydrogen, hydroxyl, (C1-C8) -alkyloxy or (C1-C8) -alkyl-for the treatment and prevention of endometrosis. Some particularly favorable embodiments of the present invention are the following compounds as reported in WO2004 / 055031: acid (5-Chloro-2- { 2- [4- (4-fluoro-benzyl) - (2R, 5S) - 2,5-dimethyl-piperazin-1-yl] -2-oxo-ethoxy.] - benzyl) -phosphonic acid monoethyl ester (5-Chloro-2-. {2- [4- (4- fluoro-benzyl) - (2R, 5S) -2,5-dimethyl-piperazin-1-yl] -2-oxo-ethoxy.] - benzyl) phosphonic acid, 5-chloro-2-acid. { 2- [4- (4-Fluoro-benzyl) - (2R5S) -2,5-dimethyl-piperazin-1-yl] -2-oxo-ethoxy} -benzyl) -phosphonamide In another aspect, this invention provides pharmaceutical compositions useful for the treatment of endometrosis in a female human in need of such treatment, and said composition comprises a therapeutic effective amount of a compound of formula ( la) as described, and an excipient acceptable for pharmaceutical use. In another aspect, this invention provides a method for treating and preventing endometrosis in a female human, and said method comprises administering to a female human in need of such treatment a therapeutic effective amount of a compound of the formula ) as described. In another aspect, this invention provides compounds of formula (la) for the preparation of a medicament for the treatment of endometrosis. BRIEF DESCRIPTION OF THE FIGURES Other features and advantages of the invention will be apparent from the following description of some favorable forms of embodiments of the invention, which are given as purely non-restrictive examples, with reference to the accompanying figures, wherein : Figure 1 shows the location of CCR1 in endometriotic lesions and endometrial tissue. In endometriotic-peritoneal lesions the chemokine receptor CCR1 is located in immune cells that infiltrate the tissue (A-D). No immune cells expressing CCRl were detected in the endometrium of patients with endometrosis (E) as well as in the endometrium of non-endo-metricsic controls (G). Negative control (F, H). Figure 2 shows the data from the analysis of the ex-pressure of mRNA of CCRl in endometriotic lesions and in endometrium from patients with endometrosis. Controls: Lines 1, 2 and 3 represent the endometrium from non-endometriosis women. In such tissue samples the expression of CCR1 mRNA is low. Bands 4-9 are tissue samples from women with endometrosis. In parentheses: endometrium and endometriotic lesion from the same patient.

The expression of CCR1 mRNA is sensitized in endometriotic lesions (lines 5, 7, 9) compared to the endometrial sample (lines 4, β, 8). Figure 3 shows the characterization of intracellular cells expressing CCR1. Co-immunostaining with monoclonal antibodies to CCR1 (Figs A and D), CD4 (Fig. 4B) and CD68 (Fig. 4E) confirm that the chemokine receptor CCR1 is expressed in monocytes, and macrophages (CD68) T cells helpers (CD4) (Figs 4C and F). Figure 4 shows the effects of the CCRl antagonist on the area and volume of peritoneal endometriotic lesions in rats with experimental induced endometrosis. Controls: white bar: animals were treated for 4 weeks with vehicle, propylene glycol (0.5mg / kg). Dotted bar: The animals received an antiestrogen (llß-Fluoro-7a- (14, 14, 15, 15, 15-pentafluoro-β-methyl-10-thia-6-azapentadecyl) estra-1, 3.5 (10) -triene-3, 17β-diol) (lmg / kg). Scratched bar: The animals were treated with a CCR1 antagonist according to the present application and in particular with (2R) -l-. { [4-chloro-2- (ureido) phenoxy] methyl} carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine as the sulfate salt (50mg / kg). Compared with vehicle control, the data show that the compounds according to the present invention reduce the effects on the area and volume of peritoneal endometriotic cysts in rats. Figures 5 and 5a show the expression of mRNA of CCRl in the model of endometrosis in rats. Figure 5 shows the expression of CCR1 mRNA in endometriotic mesenteric and peritoneal cysts. As controls, rat uteri and rat ovaries were used (1-3 animal 1; 4-7 animal 2). Compared with the uteri and ovaries, the expression of CCRl mRNA is sensitized in the peritoneum and mesentery cysts. Figure 5a shows the expression of the RANTES ligand of CCR1 in treated and untreated animals. Control group (untreated animals): high expression of RANTES in mesenterial and peritoneal lesions. After 3 weeks of treatment, treatment with CCRl antagonists induces significant down-regulation of RANTES mRNA in peritoneal and mesenterial cysts in rats. The results represent the average values of three animals. Figures 6 and ßa: number and location of cells with the CCR1 stained in the endometrium and grafts / endometriotic lesions of Rhesus monkey. Figure 6: positive counts for CCR1 in cells. The cell counts represent the average number of positive CCRl cells per section counted with an ocular grid. The cells were identified by immunohistochemical staining. In six sections, n = 3 animals were counted. The number of cells expressing CCR1 is upregulated in endometriotic grafts during the menstrual cycle in rhesus monkeys. Figure 6a: Localization of the cells with the CCR1 stained in grafts / endometriotic lesions and in the endometrium. Compared to the endometrium, the number of cells expressing CCRl is increased in endometriotic lesions / grafts.

DETAILED DESCRIPTION OF THE INVENTION Definitions As used in the specification and the appended claims, unless otherwise indicated, the following terms have the meanings indicated: "Alkyl" refers to a monovalent or divalent radical linear or branched chain lens consisting exclusively of carbon and hydrogen, with no unsaturation and with between one and eight carbon atoms, for example, methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n-butyl , n-pentyl, 1, 1-dimethylethyl (t-butyl), n-heptyl, and the like. "Alkylcarbonyl" refers to a radical of the formula -C (0) -Ra where Ra is an alkyl radical as defined, for example, acetyl, ethylcarbonyl, n-propylcarbonyl, and the like. "Alkylcarbonylalkyl" refers to a radical of the formula - Ra-C (0) -R where each Ra is independently an alkyl radical as defined, for example, (acetyl) methyl, 2- (acetyl) ethyl, 4- (ethylcarbonyl) butyl, and the like. "Alkylcarbonylamino" refers to a radical of the formula -N (H) -C (O) -Ra where Ra is an alkyl radical as defined, for example, acetylamino, ethylcarbonylamino, n-propylcarbonylamino, and the like. "(Alkylcarbonyl) (alkyl) amino" refers to a radical of the formula -N (Ra) -C (O) -Ra where each Ra is independently an alkyl radical as defined, for example, N-methyl -N-acetylamino, N-ethyl-N- (ethylcarbonyl) amino, and the like. "Alkylcarbonylaminoalkyl" refers to a radical of the formula - Ra - N (H) C (0) - Ra where each Ra is independently an alkyl radical as defined, for example, acetylamomethyl, 2- (acetylamino) ethyl , 4- (ethylcarbonylamino) butyl, and the like. "(Alkylcarbonyl) (alkyl) aminoalkyl" refers to a radical of the formula -Ra ~ N (Ra) -C (0) -Ra where each Ra is independently an alkyl radical as defined, for example , (N-methyl-N-acetylamino) ethyl, 2- (N-ethyl-N- (ethylcarbonyl) araino) propyl, and the like. "Alkylthio" refers to a radical of the formula -S-Ra where Ra is an alkyl radical as defined, for example, methylthio, ethylthio, n-propylthio, and if not. "Alkylsulfinyl" refers to a radical of the formula -S (0) Ra where R a is an alkyl radical as defined, for example, methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, and the like. "Alkylsulfonyl" refers to a radical of the formula -S (0) 2Ra where Ra is an alkyl radical as defined, for example, methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, and the like.

"Alkylthioalkyl" refers to a radical of the formula -R a S-Ra where each Ra is independently an alkyl radical as defined, eg, methylthiomethyl, 2-methylthioethyl, 2-ethylthiopropyl, and the like. . "Alkylsulfinylalkyl" refers to a radical of the formula -R a-S (0) -Ra where each Ra is independently an alkyl radical as defined, e.g. ex. , methylsulfinylmethyl, 2-methylsulfinylethyl, 2-ethylsulfinylpropyl, and the like. "Alkylsulfonylalkyl" refers to a radical of the formula -Ra-S (O) 2-Ra wherein each Ra is independently an alkyl radical as defined, eg, methylsulfonylmethyl, 2-methylsulfonylethyl, 2-ethylsulfonylpropyl , and similar. "Alkylsulfonylamino" refers to a radical of the formula -N (H) -S (O) 2-Ra where Ra is an alkyl radical as defined, eg, methylsulfonylamino, ethylsulfonylamino, iso-propylsulfonylamino, and the like . "Alkylsulfonylaminoalkyl" refers to a radical of the formula -Ra-N (H) -S (O) 2-Ra wherein each Ra is independently an alkyl radical as defined, eg, methylsulfonylaminomethyl, 2- (ethylsulphenylamino) ethyl, 3- (iso-propylsulphonylamino) ropyl, and the like. "(Alkylsulfonyl) (alkyl) aminoalkyl" refers to a radical of the formula -Ra-N (Ra) -S (0) 2-Ra wherein each Ra is independently an alkyl radical as defined, e.g. ., (methylsulfonyl) (methyl) aminomethyl, 2- ((ethylsulfonyl) (methyl) amino) ethyl, 3- ((isopropylsulfonyl) (ethyl) amino) propyl, and the like. "Alkenyl" refers to a straight or branched chain monovalent or diolvalent radical consisting exclusively of carbon and hydrogen, containing at least one double bond and having between two and eight carbon atoms, eg, ethenyl, prop-1-enyl, but-1-enyl, pentyl-enyl, penta-1,4-dienyl, and the like. "Alkenylcarbonylamino" refers to a radical of the formula -N (H) -C (O) -Rc where R c is an alkenyl radical as defined, e.g. ex. , etenilcarbonilarrd.no, prop-2-enylcarbonylamino, but-2-enylcarbonylamino, and the like. "Alkynyl" refers to a straight or branched chain monovalent or divalent radical consisting exclusively of carbon and hydrogen, containing at least one triple bond and having between two and eight carbon atoms, eg, ethinyl, propyl 1-inyl, but-1-ynyl, pent-1-ynyl, pent-3-ynyl, and the like. "Alkoxy" refers to a radical of the formula -ORa where R a is an alkyl radical as defined. for example, methoxy, ethoxy, n-propoxy, 1-methylethoxy (iso-propoxy), n-butoxy, n-pentoxy. 1,1-dimethylethoxy (t-butoxy), and the like. "Alkoxycarbonyl" refers to a radical of the formula -C (0) ORa where Ra is an alkyl radical as defined, for example, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, and the like. "Alkoxycarbonylalkyl" refers to a radical of the formula -Ra-C (0) ORa where each Ra is independently an alkyl radical as defined, e.g. ex. , methoxycarbonylmethyl, 2- (ethoxycarbonyl) ethyl, 2- (methoxycarbonyl) propyl, and the like. "Alcoxialguilcarbonyloxyalkyl" refers to a radical of the formula -Ra-OC (O) -Ra-ORa where each Ra is independently an alkyl radical as defined, for example, methoxymethylcarbonyloxymethyl, 2- (2- ( 2- (ethoxy) ethylcarbonyloxy) ethyl) ethyl, 2- (3- (2- (ethoxy) ethylcarbonyloxy) propyl) ethyl, and the like. "Alkoxycarbonylamino" refers to a radical of the formula - (H) -C (O) -0Ra where Ra is an alkyl radical as defined, eg, methoxycarbonylamino, ethoxycarbonylamino, isopropoxycarbonylamino, and the like. "(Alkoxycarbonyl) (alkyl) amino" refers to a radical of the formula -N (Ra) (C (O) OR a) wherein each Ra is independently an alkyl radical as defined, for example, N-methyl-N-methoxycarbonylamino, N-ethyl-N-ethoxycarbonylamino, and the like. "Alkoxycarbonylaminoalkyl" refers to a radical of the formula - Ra-? (H) -C (O) -ORa where each Ra is independently an alkyl radical as defined, e.g., methoxycarbonylaminomethyl, 2- (ethoxycarbonylarrd.no) ethyl, isopropoxycarbonylaminometyl, and the like. "(Alkoxycarbonyl) (alkyl) aminoalkyl" refers to a radical of the formula - Ra-? (Ra) (C (0) 0Ra) wherein each Ra is independently an alkyl radical as defined, eg, N-methyl-N-methoxycarbonylaminomethyl, 2- (N-ethyl- N- ethoxycarbonyl) ethyl), and the like. "(Alkoxy) aralkyl" refers to an aralkyl radical wherein the alkyl group therein is substituted by an alkoxy radical as defined, for example, 2-phenyl-1-methoxyethyl, phenyl (methoxy) methyl, and the like . "Alkoxyalkylcarbonylarrd.no" refers to a radical of the formula -N (H) -C (0) - Ra-0-Ra where each Ra is an alkyl radical as defined, for example, methoxymethylcarbonylamino, ethoxyethylcarbonylaryl. no, methoxyethyl-carbonylamino, and the like. "Alkoxycarbonylalkylcarbonylamino" refers to a radical of the formula -N (H) -C (O) -Ra-C (O) 0Ra wherein each Ra is independently an alkyl radical as defined, eg, ethoxycarbonylmethylcarbonylaird. no, methoxycarbonylmethylcarbonylamino, (2-ethoxycarbonyl ethyl) carbamylamino, (2-methoxycarbonylethyl) carbonylamino, and the like. "Alkoxycarbonylalkylcarbonylaminoalkyl" refers to a radical of the formula -Ra-N (H) -C (O) -Ra-C (O) 0Ra where each Ra is independently an alkyl radical as defined, e.g. , ethoxycarbonylmethylcarbonylaminomethyl, 2- (methoxycarbonylmethylcarbonylamino) ethyl, 1- ((2-ethoxycarbonylethyl) carbonylamino) ethyl, (2-methoxycarbonylethyl) carbonylaminomethyl, and the like. "(Alkoxycarbonylalkyl) aminocarbonyl" refers to a radical of the formula -C (O) - (H) -Ra-C (O) -OR where each Ra is independently an alkyl radical as defined, for example , (methoxycarbonylmethyl) aminocarbonyl, (2- (ethoxycarbonyl) ethyl) aminocarbonyl, (1- (methoxycarbonyl) ethyl) aminocarbonyl, and the like. "(Alkoxycarbonylalkyl) ureidoalkyl" refers to a radical of the formula -Ra- (H) -C (0) -N (H) -Ra-C (0) -0Ra wherein each Ra is independently an alkyl radical according to it has been defined and where the nitrogen to which -Ra-C (0) -0Ra is attached is indicated as "N" ', eg, (ethoxycarbonylmethyl) ureidomethyl, (2- (ethoxycarbonyl) ethyl) ureidomethyl, 2- ((2- (ethoxycarbonylmethyl) ureidomethyl, and the like. "(Alkoxycarbonylalkylcarbonyl) (alkyl) glycinamide" refers to a radical of the formula - (H) -C (O) ~ CH2-? (R a) -C (0) ) -Ra- C (0) -0Ra where each Ra is independently an alkyl radical as defined, eg, (methoxycarbonylmethylcarbonyl) (methyl) glycinamide, ((2-ethoxycarbonylethyl) carbonyl) (ethyl) glycinamide , and the like. "(Alkoxyalkylcarbonyl) glycinamide" refers to a radical of the formula - (H) -C (0) -CH2-? (H) -C (0) -R a-0-Ra where each Ra is independently an alkyl radical as defined, e.g., (methoxyacetyl) glycinamide, (ethoxyacetyl) glycinamide, and the like. "Alkylene chain" refers to a branched or straight chain divalent radical consisting exclusively of carbonyl and hydrogen, unsaturated and having between one and eight carbon atoms, eg, methylene, ethylene, propylene, n-butylene, and similar. "Alkylidene chain" refers to a branched or straight chain unsaturated divalent radical consisting exclusively of carbon and hydrogen atoms, with between one and eight carbon atoms, wherein the unsaturation is present only in the form of double bonds and where there may be a double bond between the first carbon in the chain and the rest of the molecule, eg. , ethylidene, propylidene, n-butylidene, and the like. "Amino" refers to the radical -NH2. "Aminoalkyl" refers to a radical of the formula - RaNH2 where R a is an alkyl radical as defined, for example, aminomethyl, 2-aminoethyl, 3-aminopropyl, 2-aminopropyl, and the like. "Aminoalkylamino" refers to a radical of the formula -N (H) - Ra-NH2 where R a is an alkyl radical as defined, e.g., aminomethylamino, (2-aminoethyl) amino, (2-ami? opropyl) amino, and the like. "Aminoalkoxy" refers to a radical of the formula - ORa - NH2 where Ra is an alkyl radical as defined, eg, aminomethoxy, 2-aminoethoxy, 3-amino-propoxy, 2-aminopropoxy, 4-aminobutoxy , and similar. "Aminocarbonyl" refers to the radical -C (0) NH2. "Aminocarbonylglycinamide" refers to a radical of the formula -N (H) -C (O) -CH2-N (H) -C (O) -NH 2. "(Aminocarbonyl) (alkyl) glycinamide" refers to a radical of the formula -N (H) -C (O) -CH2-N (Ra) -C (0) -NH2 wherein Ra is an alkyl radical as defined and wherein the nitrogen with the substituent R a is designated as "N", p. ex. , (aminocarbonyl) (N '-methyl) glycinamide, (aminocarbonyl) (N'-ethyl) glycinamide, and the like. "Aminocarbonylalkyl" refers to a radical of the formula - Ra-C (0)? H 2 where Ra is an alkyl radical as defined, e.g., aminocarbonylmethyl, 2- (aminocarbonyl) ethyl, 2- (aminocarbonyl) propyl, and the like. "(Aminocarbonylalkyl) aminocarbonyl" refers to a radical of the formula - C (O) -? (H) -Ra-C (O) -? H2 where Ra is an alkyl radical as defined, e.g., (aminocarbonylmethyl) aminocarbonyl, (2-aminocarbonyl ethyl) aminocarbonyl, (1-aminocarbonylethyl) aminocarbonyl, and similar. "(Aminoalkyl) aminocarbonyl" refers to a radical of the formula -C (0) -N (H) -R a -NH 2 where Ra is an alkyl radical as defined, eg, (aminomethyl) aminocarbonyl, ( 2-aminoethyl) aminocarbonyl, (1-aminoethyl) aminocarbonyl, and the like. "Amidino" refers to the radical -C (NH) NH2. "Aryl" refers to a phenyl or naphthyl radical. Unless expressly indicated otherwise in the specification, the term "aryl" or the prefix "ar-" (for example in "aralkyl") are intended to include aryl radicals optionally substituted by one or more substituents selected from the group formed by hydroxy, mercapto, halo, alkyl, alkenyl, alkynyl, phenyl, phenylalkyl, phenylalkenyl, alkoxy, phenoxy, phenylalkoxy, haloalkyl, haloalkoxy, formyl, nitro, cyano, amidino, cycloalkyl, hydroxyalkyl, alkoxyalkyl, phenoxyalkyl, phenylalkoxyalkyl, amino, - noalquilamino, dialkylamino, monophenylamino, monofeni- lalquilamino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, monophenylaminoalkyl, monofeni- lalquilaminoalquilo, alkylcarbonyl, carboxy, carbonyl alkoxy-, carpoxialquilo, alkoxycarbonylalkyl, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, aminocarbonylalkyl, monoalquilaminocarbo- nilalquilo, dialkylaminocarbonylalkyl, as it is defined in the present. "Arylcarbonyl" refers to a radical of the formula -C (0) Rb where Rb is an aryl radical as defined, for example, phenylcarbonyl and naphthalene-2-ylcarbonyl, and the like. "Arylcarbonylalkyl" refers to a radical of the formula -RaC (O) Rb where Ra is an alkyl radical as defined and Rb is an aryl radical as defined, eg, phenylcarbonylmethyl, 2- (phenylcarbo- nil) ethyl, 3- (naphthalen-2-ylcarbonyl) propyl, and the like. "Arylcarbonylaminoalguyl" refers to a radical of the formula --Ra-N (H) -C (O) -R b where Ra is an alkyl radical as defined and Rb is an aryl radical as defined, eg ., (4-methoxyphenyl) carbonyl-aminomethyl, 2- ((4-fluorophenyl) carbonylamino) ethyl, 1- ((4-chlorophenyl) carbonylamino) ethyl, and the like. "Arylsuffonyl" refers to a radical of the formula -S (O) 2 -Rb where Rb is an aryl radical as defined, for example, phenylsulfonyl, (4-chlorophenyl) sulfonyl, (3-nitrophenyl) sulfonyl , and similar. "Arylsulfonylamino" refers to a radical of the formula -N (H) -S (0) 2-R where Rb is an aryl radical as defined, for example, phenylsulfonylamino, (4-chlorophenyl) sulfonylamino, (4- fluorophenyl) sulphonylamino, (3-nitrophenyl) sulfonylamino, and the like. "Arylsulfonylaminoalkyl" refers to a radical of the formula -Ra-N (H) -S (0) 2 ~ Rb where Ra is an alkyl radical as defined and Rb is an aryl radical as defined, for example, phenylsulfonylaminometyl, (4-chlorophenyl) sulfonylaminomethyl, 2- ((4-fluorophenyl) sulfonylamino) ethyl, 1- ((3-nitropnenyl) sulfonylamino) ethyl, and the like. "(Arylsulfonyl) (alkyl) aminoalkyl" refers to a radical of the formula -R aN (Ra) -S (O) 2 -Rb where each R a is independently an alkyl radical as defined and Rb is a aryl radical as defined, for example, (phenylsulfonyl) (methyl) aminomethyl, ((4-chlorophenyl) sulfonyl) (ethyl) aminomethyl, 2 - (((4-fluorophenyl) sulfonyl) (methyl) amino) ethyl, - (((3-nitrophenyl) sulfonyl) (ethyl) amino) ethyl, and the like. "(Alkoxycarbonylaminoalkylcarbonyl) glycinamide" refers to a radical of the formula -N (H) -C (O) -CH2-N (H) -C (O) -N (H) -C (O) -ORa where Ra is an alkyl radical as defined, for example, (ethoxycarbonylaminocarbonyl) glycinamide, (methoxycarbonylaminocarbonyl) glycinamide, and the like. "Arylcarbonylglycinamide" refers to a radical of the formula -N (H) -C (0) -CH2-N (H) -C (0) -Rb where Rb is an aryl radical as defined, for example, phenyl - carbonylglycinamide, (4-fluoro-3-trifluoromethylphenyl) carbonylglycinamide, (4-fluorophenyl) carbonylglycinamide, and the like. "(Arylcarbonyl) (alkyl) glycinamide" refers to a radical of the formula -N (H) -C (O) -CH2-N (Ra) -C (O) -Rb where Ra is an alkyl radical as defined and Rb is an aryl radical as defined and the nitrogen to which the radical Ra is attached is designated as "N" ', for example, (phenylcarbonyl) (N'-methyl) glycinamide, ((4- fluoro-S trifluoromethylphenyl) carbonyl) (N-ethyl) glycinamide, ((4-fluorophenyl) carbonyl) (N '-methyl) glycinamide, and the like. "Aralkyl" refers to a radical of the formula -RaRb where Ra is an alkyl radical as defined and Rb is an aryl radical as defined, for example, benzyl, and the like. "Aralkylcarbonyl" refers to a radical of the formula -C (0) -Ra where Rd is an aralkyl radical as defined, for example, benzylcarbonyl, 1- (phenyl) ethylcarbonyl, and the like. "Aralkylcarbonylalkyl" refers to a radical of the formula -RaC (0) Rd where Ra is an alkyl radical as defined and Rd is an aralkyl radical as defined, for example, benzylcarbonylmethyl, 2- (1- (phenyl) ethylcarbonyl) ethyl, and the like. "Aralkenyl" refers to a radical of the formula -RcRb where R is an aryl radical as defined and Rc is an alkenyl radical as defined, for example, 3-phenylpropyl-1-enyl, and the like. "Aryloxy" refers to a radical of the formula -OR b where Rb is an aryl radical as defined, for example, phenoxy and naphthoxy, and the like. "Aralkoxycarbonyl" refers to a radical of the formula -C (0) ORd where Rd is an aralguyl radical as defined, eg, benzyloxycarbonyl, and the like.

"Aralkoxycarbonylalkyl" refers to a radical of the formula -Ra C (0) ORd where Ra is an alkyl radical as defined and Ra is an aralkyl radical as defined, for example, benzyloxycarbonylmethyl, 2- (benzyloxycarbonyl) ethyl , 3- ((naphthalen-2-yl) oxy) carbonyl) propyl, and the like. "Aryloxyalkyl" refers to a radical of the formula 5-Ra-ORb where R a is an alkyl radical as defined and R b is an aryl radical as defined, for example, phenoxymethyl, 2- (phenoxy) ethyl, 3- (phenoxy) propyl, and the like. "Aryloxyalkylcarbonyloxyalkyl" refers to a dical radical of the formula -Ra-OC (O) -Ra-ORb where each Ra is independently an alkyl radical as defined and Rb is an aryl radical as defined, p. ex. , phenoxymethylcarbonyloxymethyl, (2-phenoxyethyl) carbonyloxymethyl, 3- ((2-phenoxyethyl) carbo-5. nyloxy) propyl, and the like. "Aralkoxy" refers to a radical of the formula -OR where R is an aralkyl radical as defined, for example, benzyloxy, and the like. "Aralkoxylalkyl" refers to a radical of the -Ra-ORd moiety where Ra is an alkyl radical as defined and Rd is an aralkyl radical as defined, for example, benzyloxymethyl, 2-phenylethoxymethyl, and similar.

"Aralkoxyalkylcarbonyloxyalkyl" refers to a radical of the formula -R a-0C (0) -Ra-ORd where each Ra is independently an alkyl radical as defined and Rd is an aralkyl radical as defined, for example, benzyloxymethylcarbonyloxymethyl, 2- (phenyl) ethoxymethyl) carbonyloxymethyl, 2- ((2- (phenyl) ethoxymethyl) carbonyloxy) ethyl, and the like. "Alkoxyalkyl" refers to a radical of the formula -Ra 0Ra where each Ra is independently an alkyl radical as defined, for example, methoxyethyl, ethoxymethyl, propoxymethyl, propoxyethyl, and the like. "Alaninamido" refers to a radical of the formula - N (H) -C (0) -C (CH3) H-NH 2. "Alanimamidoalkyl" refers to a radical of the formula -R aN (H) -C (O) -C (CH 3) H-NH 2 where Ra is an alkyl radical as defined, for example, alanine-midomethyl, 2- (alaninamido) ethyl, 1- (alaninamido) ethyl, 3- (alaninamido) propyl, and similar. "Azidoalkyl" refers to a radical of the formula -R a-N3 where Ra is an alkyl radical as defined, for example, 2-azidoethyl, 3-azidopropyl, 2-azidopropyl, 4-azidobutyl, and the like.

"Benzyl" refers to a radical of the formula -CH2-Rh where Rh is a phenyl radical that is optionally substituted by one or more substituents selected from the group consisting of hydroxy, halo, alkyl, haloalkyl, alkoxy, alkenyl, nitro, cyano, amino, monoalkylamino, dialkylamino, alkylcarbonyl, carboxy, alkoxycarbonyl, and aminocarbonyl. "Benzylcarbonyl" refers to a radical of the formula -C (0) -CH2-Rh where Rh is a phenyl radical as defined, for example, (4-methoxybenzyl) carbonyl, (3-fluorobenzyl) carbonyl, and the like . "Carboxi" refers to the radical -C (0) 0H. . "Carboxyalkyl" refers to the radical of the formula -Ra ~ C (0) OH where Ra is an alkyl radical as defined, for example, carboxymethyl, 2-carboxyethyl, 3-carboxypropyl, and the like. "(Carboxyalkyl) aminocarbonyl" refers to a radical of the formula -C (O) -N (H) -Ra-C (O) OH where R a is an alkyl radical as defined, for example, (carboxymethyl) aminocarbonyl, '(2-carboxyethyl) aminocarbonyl, (1-carboxyethyl) aminocarbonyl, and the like. "Carbocyclic ring system" refers to a stable radical of 3 to 15 members consisting exclusively of carbon and hydrogen atoms. For the purposes of this invention, the carbocyclic ring system radical can be a monocyclic, bicyclic or tricyclic ring system, and can include fused or bridged ring systems, and the ring system can be partially or fully saturated or aromatic, and the carbon atoms in the ring system can optionally be oxidized. Examples of such carbocyclic ring system radicals include, without limitation, cyclopropyl, cyclobutyl, cyclohexyl, norbornane, norbornene, adamantyl, bicyclo [2.2.2] octane, phenyl, naphthyl, indenyl, azulenyl, fluorenyl, anthracenyl, and the like. "Cycloalkyl" refers to a stable monocyclic or bicyclic radical of 3 to 10 members which is saturated, and which consists exclusively of carbon and hydrogen atoms, for example, cyclopropyl, cyclobutyl, cyclobutyl, cyclohexyl, decalinyl and the like. Unless specifically indicated otherwise in the descriptive specification, the term "cycloalkyl" is intended to include cycloalkyl radicals which are optionally substituted by one or more substituents selected independently from the group consisting of alkyl, halo, hydroxy, amino, nitro , alkoxy, carboxy, phenyl and alkoxycarbonyl. "Cycloalkylalkyl" refers to a radical of the formula -Ra-Re where Ra is an alkyl radical as ned and Re is a cycloalkyl radical as ned, for example, cyclopropylmethyl, 2-cyclobutyl-ethyl, 3-cyclohexylpropyl , and similar. "Cycloalkylamino" refers to a radical of the formula -N (H) -Re where Re is a cycloalkyl radical as ned, for example, cyclopropylaryl, cyclobutylamino, cyclohexylarrd.no, and the like. "Cycloalkylaminoalguyl" refers to a radical of the formula -R aN (H) -R e where Ra is an alkyl radical as ned and Re is a cycloalguyl radical as ned, eg, cyclopropylaminomethyl, 2- (cyclobutylamino) ethyl, cyclohexylaminomethyl, and the like. "(Cycloalkylalkyl) amino" refers to a radical of the formula -N (H) -Ra-Re where Ra is an alkyl radical as ned and Re is a cycloalkyl radical as ned, eg, (cyclopropylmethyl) amino, (2-cyclobutylethyl) a, (3-cyclohexylpropyl) amino, and the like.

"(Cycloalkylalkyl) aminoalkyl" refers to a radical of the formula -R aN (H) -Ra-Re wherein each Ra is independently an alkyl radical as defined and Re is a cycloalkyl radical as defined above. finido, p. ex. , (cyclopropylmethyl) aminomethyl, '2 - ((2-cyclobutylethyl) amino) ethyl, (3-cyclohexylpropa) aminomethyl, and the like. "Cycloalkylcarbonylamino" refers to a radical of the formula -C (0) -N (H) -Re where Re is a cycloalkyl radical as defined, for example, cyclopropyl-carbonylamino, (2-phenylcyclopropyl) carbonylamino , cyclohexylcarbonilarrd.no, 4-cyanodecanylcarbonylamino. cyclopentylcarbonylaird.no, and the like. "Cycloalkylcarbonylaminoalkyl" refers to a radical of the formula -Ra-C (O) -N (H) -Re where R a is an alkyl radical - as defined and Re is a cycloalkyl radical as defined, for example, cyclopropylcarbonylaminomethyl, 2- ((2-phenylcyclopropyl) carbonylamino) ethyl, 1- (cyclohexylcarbonylamino) ethyl, (3-phenylcyclopentyl) carbonylaminomethyl, and the like. "Cycloalkylalkylcarbonylamino" refers to a radical of the formula -C (0) - N (H) -Ra-Re wherein R a is an alkyl radical as defined and Re is a cycloalkyl radical as defined, for example, (cyclopropylmethyl) carbonyl amino, ((2-phenylcyclopropyl) methyl) carbonylamino, (2-cyclohexylethyl) carbonylamino, (1-cyclohexylethyl) carbonylamino, and the like. "Ciano" refers to the radical -CN. "Cyanoalkyl" refers to a radical of the formula - RaCN where Ra is an alkyl radical as defined, cyanomethyl, 2- (cyano) ethyl, 3- (cyano) propyl, and the like. "DMF" refers to N, N-dimethylformamide. "DMSO" refers to dimethylsulfoxide. "Dialkylamino" refers to a radical of the formula -N (R a) Ra don-de. each Ra is independently an alkyl radical as defined, for example, dimethylamino, methylethylamino, diethylamino, dipropylamino, ethylpropylamino, and the like. . . . ' "Dialkylaminoalkyl" refers to a radical of the formula -Ra-N (Ra) R "where each Ra is independently an alkyl radical as defined, eg, dimethylaminomethyl, methylethylaminomethyl, 2-diethylaminoethyl , 3-dipropylaminopropyl, and the like. "Dialkylaminocarbonyl" refers to a radical of the formula -C (0) N (Ra) Ra wherein each Ra is independently an alkyl radical as defined, for example, dimethylaminocarbonyl, methylethylaminocarbonyl, diethylaminocarbonyl, dipropylaminocarbonyl, ethylpropylaminocarbonyl, and the like. "Dialkylaminocarbonylalkyl" refers to a radical of the formula -Ra-C (0) N (Ra) Ra- wherein each Ra is independently a radical alkyl as defined, eg, dimethylaminocarbonylmethyl, 2- (methylethylaminocarbonyl) ethyl, 3- (diethylalkylcarbonyl) propyl, 2- (dipropylaminocarbonyl) propyl, and the like. "Dialguilaminocarbonyloxyalkyl" refers to a radical of the form ula -R a-0-C (O) -N (Ra) Ra wherein each Ra is independently an alkyl radical as defined, e.g. ex. , dimethylaminocarbonyloxymethyl, 2- (etylethylaminocarbonyloxy) ethyl, -3- (diethylaminocarbonyl-oxy) propyl, 2- (dipropylaminocarbonyloxy) propyl, and the like. "Dialkylureido" refers to a radical of the formula -N (H) -C (0) -N (Ra) (Ra) or a radical of the formula -N (Ra) -C (O) -N (Ra) H wherein each Ra is independently an alkyl radical as defined and and the linking nitrogen is designated as "N" and the other nitrogen is designated as "N", for example, N ', N' -di ( methyl) ureido, N'-methyl-N'-ethylureido, N ', N'-di (ethyl) ureido, N', N'-di (propyl) ureido, N-methyl-N'-ethylureido, and the like. "Diarilureide" refers to a radical of the formula -? (H) -C (0) -? (Rb) (Rb) or a radical of the formula -? (Rb) - C (0) -? (Rb) H where each Rb is independently an aryl radical as defined and the binding nitrogen is designated "N" and the other nitrogen is designated "N", for example, N ', N'-di (phenyl) ureido, N'-f-enyl-N' - (3-nitro) phenylureido, N ', N'-di (4-methoxyphenyl) ureido,. N ', N -'- di (4-chlorophenyl) ureido, N-4-chlorofenyl-N' - (3-chlorophenyl) ureido and the like. "Dialkylureidoalkyl" refers to a radical of the formula -R a-? (H) -C (O) -? (Ra) (Ra) or - a radical of the formula -R a-? (Ra) .- C (O) -? (-a) H wherein each Ra is independently a -radical alkyl as defined and the attached nitrogen is designated as "N" and the other nitrogen is designated as "N" ', for example, N' N'- di (methyl) ureidomethyl, 2- (N'-methyl-N '-' ethylureido) ethyl, 1- (N ', N' -di (ethyl) ureido) ethyl, 3- (N ', N' ~ di ( propyl) ureido propyl, 2- (N-methyl-N'-ethylureido) ethyl, and the like.

"Formyl" refers to the radical -C (0) H. "Formylalkyl" refers to a radical -Ra-C (0) H wherein Ra is an alkyl radical as defined, for example, formylmethyl, 2- (formyl) ethyl, 3- (formyl) propyl, and the like. "Glycinamido" refers to a radical of the formula - N (H) -C (0) -CH2-NH2. "Glycinamidoalkyl" refers to a radical of the formula -Ra-N (H) -C (0) -CH2-NH2 where R a is an alkyl radical as defined, for example, glycinamido-methyl. 2- (glycinamide) ethyl, 1- (glycinamide) ethyl, 3- '(glycinamide) propyl, and the like. "Guanidino" refers to the radical -N (H) -C (NH) -NH 2. "Halo" refers to bromine, chlorine, iodine or fluoro. "Haloalkyl" refers to an alkyl radical, as defined, which is substituted with one or more halo radicals, as defined, for example, trifluoromethyl, difluoromethyl, trichloromethyl, 2-trifluoroethyl, 1-fluoromethyl-2 -fluoroethyl, 3-bromo-2-fluoropropyl, l-bromomethyl-2-bromoethyl, and the like. "Haloalkoxy" refers to a radical of the formula -OR f where Rf is a haloalkyl radical as defined, for example, trifluoromethoxy, difluoromethoxy, trifloromethoxy, 2,2,2-trifluoroethoxy, 1-fluoromethyl-2 - fluoroethoxy, 3-bromo-2-fluoropropoxy, 1-bromomethyl-2-bromoethoxy, and the like. "Haloalkylcarbonylamino" refers to a radical of the formula -N (H) -C (0) -Rf where Rf is a haloalkyl radical as defined, for example, trifluoromethylcarbonilarrd.no, trifluoromethylcarbonilarrd.no, 2-bromoethylcarbonylamino , and similar. "(Haloalkylcarbonyl) ureido" refers to a radical of the formula -N (H) -C- (0) -N (H) -C (O) -Rf wherein Rf is a haloalkyl radical as defined, e.g. eg, (trichloromethylcarbonyl) ureido, (3-fluoropropylcarbonyl) ureido, and the like. "(Haloalkyl) (alkyl) ureidoalkyl" refers to a radical of the formula -Ra-N (Ra) -C (O) -N (H) -Rf or to a radical- of the formula -Ra- N (Rf) -C (O) -N (H) -Ra or a radical of the formula -Ra-N (H) -C (O) -N (Ra) Rf where each R a is independently an alkyl radical as defined and Rf is a haloalkyl radical as defined and the terminal nitrogen is designated. as "N" 'and the other nitrogen is designated as "N", eg, N' - (2-chloroethyl) -N- (methyl) 'ureidomethyl, and 2- (N'- (2-chloroethyl) ) -N- (methyl) ureido) ethyl, and the like.

"Haloalkylcarbonylaminoalkyl" refers to a radical of the formula -R aN (H) -C (0) -Rf wherein R a is an alkyl radical as defined and Rf is a haloalkyl radical as defined, for example, trifluor - romethylcarbonylaminomethyl, 2- (trifluoroethylcarbonylamino) ethyl, and the like. "Hydroxy" refers to the radical. -OH "Hydroxyalkyl" refers to an alkyl radical as defined to be substituted by a hydroxy radical, example, hydroxymethyl, 2-hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl, 4-hydroxybutyl, 3-hydroxybutyl, and the like. "(Hydroxyalkyl) aminocarbonyl" refers to a radical of the formula -C (0) -N (H ) -Ra-OH where Ra is an alkyl radical as defined, for example, hydroxymethylaminocarbonyl, (2-hydroxyethyl) aminocarbonyl, (1-hydroxyethyl) aminoccarbonyl, and the like. "Hydroxyalkoxy" refers to a radical of the formula -0R'a-0H where Ra is an alkyl radical as defined finido, for example, 2-hydroxyethoxy, 2-hydroxypropoxy, 4-hydroxybutoxy, 3-hydroxybutoxy, and the like. "(Hydroxyalkoxy) carbonyl" refers to a radical of the formula -C (0) -0Ra-0H where Ra is an alkyl radical as defined, for example, (2-hydroxyethoxy) carbonyl, (2-hydroxypropoxy) carbonyl , (4-hydroxybutoxy) carbonyl, (3-hydroxybutoxy) carbonyl, and the like. "(Hydroxy) aralkyl" refers to an aralkyl radical as defined wherein the alkyl radical therein is substituted by a hydroxy radical, for example, (phenyl) (hydroxy) methyl, 2-phenyl-1-hydroxyethyl, 2-phenyl-3-hydroxypropyl, and the like. "(Hydroxyalkylthio) alkyl" refers to an alkylthioalkyl radical as defined to be substituted with a hydroxy radical, for example, 2-hydroxyethylthio ethyl, 2- (hydroxymethylthio) ethyl, and the like. "Hydroxyalkenyl" refers to an alkenyl radical as defined to be substituted with a hydroxy radical, for example, 3-hydroxyprop-1-enyl, 4-hydroxybut-1-enyl, 4-hydroxypent-1-enyl, 5- hydroxypenta-1, 3-dienyl, and -like. "Hydroxyalkynyl" refers to an alkynyl radical as defined to be substituted with a hydroxy radical, for example, 3-hydroxypropyl, 4-hydroxy-pent-2-ynyl, 1-hydroxybut-3-ynyl, and the like . "(Hydroxy) cycloalkylalkyl" refers to a radical of the formula - Ra (0H) -Re where R a is an alkyl radical as defined and Re is a cycloalkyl radical as defined and where the radical OH is a substituent on any carbon of the Ra radical, eg, 2-cyclopropyl-1-hydroxyethyl, - (4-hydroxycyclohexyl) methyl, and the like. "Hydroxyalkylaminoalkyl" refers to a monoalkylaminoalkyl radical as defined below is substituted with a hydroxy radical, e.g., 2-hydroxyethylaminomethyl, 2- (3-hydroxypropylamino) ethyl, and the like. "Hydroxyamidino" refers to a radical of the formula - C (NH 2) = N0H. "Heterocyclic ring system" refers to a stable 3 to 15 member radical consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur. For the purposes of this invention, the heterocyclic ring system radical may be a monocyclic, bicyclic or tricyclic ring system, which may include fused or bridged ring systems; and the nitrogen, carbon or sulfur atoms in the heterocyclic ring system radical may be optionally oxidized; the nitrogen atom may optionally be quaternized; and the heterocyclic ring system may be partially or fully saturated or aromatic, the heterocyclic ring system may be attached to the main structure in any heteroatom or carbon atom resulting in the creation of a stable compound. Examples of such heterocyclic radicals include, without limitation, azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl,. benzopyranyl, benzopyranonyl, benzofura-nyl, benzofuranonyl, benzothienyl, carbazolyl, cin-nolinyl, decahydroisoquinolyl, dioxolanyl, furanyl, isothiazolyl, quinuclidinyl, imidazolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, indolyl, isoindolyl, indolinyl, isoindolinyl, indanyl, indolizinyl, isoxazolyl, isoxazolidinyl, morpholinyl, naphthyridinyl, oxadiazolyl, octahydroindolyl, octahydroisodinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxoazepinyl, oxazolyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, fe-nazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, -quinazolinilo, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, thiazolyl, thiazolidinyl, thiadiazolyl, triazolyl, tetrazolyl, tetrahydrofuryl, triazinyl, tetrahydropyranyl , thienyl, thiamorpholinyl, thiamorpholinyl sulf rust, and morfolinilsulfona thia. "Heterocyclyl" refers to a heterocyclic ring system as defined. Unless expressly stated otherwise in the specification, the term "heterocyclyl" is intended to include a heterocyclic ring system as defined, which is optionally substituted by one or more substituents selected from the group consisting of hydroxy, mercapto, halo , alkyl, alkenyl, alkynyl, phenyl, phenylalkyl, phenylalkenyl, alkoxy, phenoxy, phenylalkoxy, haloalkyl, haloalkoxy, formyl, nitro, cyano, amidino, cycloalkyl, hydroxyalkyl, alkoxyalkyl, phenoxyalkyl, phenylalkoxyalkyl, amino, monoalkylamino, dialkylamino, monophenylamino, monophen - lalquilamino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, monophenylaminoalkyl, monofeni- lalquilaminoalquilo, carboxy, alkoxycarbonyl, phenyl- carbonyl, benzylcarbonyl, alkylcarbonyl, carboxyalkyl chyle, alkoxycarbonylalkyl, aminocarbonyl, monoal- quilaminocarbonilo, dialkylaminocarbonyl, phenylamino- carbonyl, aminocarbonyl, mo- noalquilaminocarbonilal chyl, dialkylaminocarbonylalkyl, ureido, monoalkylureido, monophenylureido, mono-benzylureido, as defined herein. "Heterocyclylalkyl" does. reference to a radical of the formula -RaRg where Ra is an alkyl radical as defined and Rg is a heterocyclyl radical as defined, e.g. , indolinylmethyl or imidazolylmethyl, and the like. "Heterocyclylamino" refers to a radical of the formula - N (H) - Rg where Rg is a heterocyclyl radical as defined, for example, oxazol-2-ylamino; p-peridin-4-ylamino, and the like. "Heterocyclylaminoalguiló" refers to a radical of the formula -Ra-N (H) -Rg where Ra is a radical-alkyl as defined and Rg is a heterocyclyl radical as defined, e.g. ex. , oxazol-2-ylamminomethyl, 2- (oxazol-2-ylamino) ethyl, piperidin-4-ylaminomethyl, 2- (piperidin-4-ylamino) ethyl, and the like. "Heterocycliccarbonylamino" refers to a radical of the formula -N (H) -C (0) ~ Rg where Rg is u 'heterocyclyl radical as defined, for example, piperidin-4-ylcarbonylamino, furan-2-ylcarbonylamino, morpholin-4-ylcarbonylane, and the like. "Heterocycliccarbonylaminoalkyl" refers to a radical of the formula -Ra-N (H) -C (0) -Rg where R a is an alkyl radical as defined and Rg is a heterocyclyl radical as defined, for example, piperazin-4-ylcarbonylaminomethyl, 2- (furan-2-ylcarbonyl-amino) ethyl, 1- (morpholin-4-ylcarbonylamino) ethyl, and the like. "Mercapto" refers to the radical -SH. "Mercaptoalkyl" refers to a radical of the formula -R a ~ SH where Ra is an alkyl radical as defined, eg, mercaptomethyl, 2-mercaptoethyl, 3-mercaptopropyl, 2-mercaptobutyl and the like. "Monoalkylamino" refers to a radical of the formula -N (H) Ra where Ra is an alkyl radical as defined, e.g. ex. , methylamino, ethylamino, propylamino, and the like. "Monoalkylaminoalkyl" refers to a radical of the formula -R a -N (H) Ra wherein each Ra is independently an alkyl radical as defined, for example, methylaminomethyl, ethylaminomethyl, 2- (propylamino) ethyl, and the like.

"(Monoalkylamino) aralkyl" refers to a radical of the formula - Rd-N (H) Ra where R a is an alkyl radical as defined and Rd is an aralkyl radical as defined, for example, (methylamino) (phenyl) methyl, 1- (ethylamino) -1- (4-methoxyphenyl) ethyl, 2- (isopropylamino) -3- (3-chlorophenyl) propyl, and the like. "Monoarylamino" refers to a radical of the formula -N (H) R where Rb is an aryl radical as defined, eg, phenylamino, (4-mexophenyl) amino, (3,4,5- tri-ethoxyphenyl) amino and the like. "Monoarylaminoalkyl" refers to a radical of the formula - Ra - N (H) Rb where Ra is an alkyl radical as defined and Rb is an aryl radical as defined, for example, phenylaminomethyl, 2- ((4 - methoxyphenyl) amino) ethyl, 3- ((3,4,5-trimethoxyphenyl) amino) propyl, and the like. "Monoaralkylamino" refers to a radical of the formula - N (H) Rd where Rd is an aralkyl radical as defined, eg, benzylamino, (3,4,5-trimethoxybenzyl) amino, (4) -chlorobenzyl) amino, and the like.

"Monoaralkylaminoalkyl" refers to a radical of the formula -Ra-N (H) Rd where Ra is an alkyl radical as defined and Rd is an aralkyl radical as defined, e.g., benzylaminomethyl, (3 - phenylpropa) aminomethyl, 2- (benzylamino) ethyl, and the like. "Monoalkylaminocarbonyl" refers to a radical of the formula -C (0) N (H) Ra where Ra is an alkyl radical as defined, for example, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, and the like. "Monoalkylaminocarbonylalkyl" refers to a radical of the formula -Ra-C (0) N (H) Ra wherein each Ra is independently an alkyl radical as defined, eg, methylaminocarbonylmethyl, 2- ( ethylaminocarbonyl) ethyl, 3- (propylaminocarbonyl) propyl, and the like. "Monoarylaminocarbonyl" refers to a radical of the formula -C (O) N (H) Rb where Rb is an aryl radical as defined, for example, phenylaminocarbonyl, (3, 4, 5- t'ris (trifluoromethoxy) phenyl) -aminocarbonyl, (4-chlorophenyl) aminocarbonyl, and the like. "Monoarylaminocarbonylalkyl" refers to a radical of the formula -Ra-C (0) N (H) Rb where Ra is an alkyl radical as defined and Rb is an aryl radical as defined, for example, phenylaminocarbonylme - lime, 2- ((4-chlorophenyl) aminocarbonyl) ethyl, 3- ((3,4,5-trimethoxyphenyl) 'aminocarbonyl) propyl, and the like.

"Monoaralkylalkylcarbonyl" refers to a radical of the formula -C (0) N (H) Rd where Rd is an aralkyl radical as defined, for example, benzylaminocarbonyl, (3, 4, 5-tris ( trifluoromethoxy) benzyl) -aminocarbonyl, (4-chlorobenzyl) aminocarbonyl, and the like. "Monoaralkylaminocarbonylalkyl" refers to a radical of the formula -Ra-C (O) N (H) Rd where Ra is an alkyl radical as defined and Rd is an aralkyl radical as defined, eg, benzylaminocarbonylmethyl, 2- ((4-chlorobenzyl) aminocarbonyl) ethyl, 3- ((3,, 5-trimethoxybenzyl) aminocarbonyl) propyl, and the like. "(Monoalkylaminocarbonylalkyl) aminocarbonyl" refers to a radical of the formula -C (O) -N (fí) -Ra-C (O) -N (H) Ra wherein each Ra 'is independently an alkyl radical as has defined, e.g., (ethylaminocarbonylmethyl) aminocarbonyl, (2- (methylaminocarbonyl) ethyl) aminocarbonyl, (1- (ethylaminocarbonyl) ethyl) aminocarbonyl, and the like. "Monoalkylalaninamide" refers to a radical of the formula -N (H) -C (0) -C (CH 3) HN (H) Ra where Ra is an alkyl radical as defined and the attached nitrogen is designated as "N" and the other nitrogen (with the Ra substituent) is designated as "N", for example, N '-methylalanimido, N'-ethylalanimido, and the like. "Monoalkyl glycinamide" refers to a radical of the formula -? (H) -C (0) -CH2-? (H) Ra wherein Ra is an alkyl radical as defined and the binding nitrogen is designated as "N" and the other nitrogen (with the Ra substituent) is designated as "N", for example, N'-methylglycinamide. N'-ethylglycinamide, and the like. "(Monoarylaminocarbonyl) glycinamide" refers to a radical of the formula -? (H) -C (0) -CH2-? (H) -C (0) - (H) Rb where Rb is an aryl radical as defined, for example, ((4-phenoxyphenyl) aminocarbo-nyl) glycinamide, ((4-chlorophenyl) aminocarbonyl) glycinamide, ( phenylamins-carbonyl) glycinamide, and the like. "(Monoarylaminocarbonyl) ('alguil) glycinamide" refers to a radical of the formula -? (H) -C (0) -CH2-? (Ra) -C (O) -? (H) Rb where Ra is an alkyl radical as defined and Rb is an aryl radical as defined and the nitrogen to which Ra is attached is designated corao "N", p . ex. , ((4-phenoxyphenyl) aminocarbonyl) (N'-methyl) glycinamide, ((4-chlorophenyl) aminocarbonyl) (N '-ethyl) glycinamide, (phenylaminocarbonyl) (N'-methyl) glycinamide, and the like.

"(Monoaralkylaminocarbonyl) glycinamide" refers to a radical of the formula - (H) -C (0) -CH2-N (H) -C (0) -N (H) R d where Rd is an aralkyl radical as has defined, for example, ((4-phenoxybenzyl) aminocarbonyl) glycinamide, ((4-chlorobenzyl) aminocarbonyl) glycinamide, (benzylaminocarbonyl) glycinamide, and the like. "(Monoaralkylaminocarbonyl) (alkyl) glycinamide" refers to a radical of the formula -N (H) -C (0) -CH2- N (Ra) -C (O) -N (H) Rd where Ra is a radical alkyl as defined and Rd is an aralkyl radical as defined and the nitrogen to which Ra is attached is designated as. "N", p. ex. , ((4-phenoxybenzyl) aminocarbonyl) (N '-methyl) glycinamide, ((4-chlorobenzyl) aminocarbonyl) (N' - etii) glycinamide, (benzylaminocarbonyl) (N '-methyl) glycinamide, and the like. "Monoalkylureido" refers to a radical of the formula -? (H) -C (0) -? (H) Ra or a radical of the formula -? (R a) -C (0) -? H2 where Ra is an alkyl radical as defined and the linking nitrogen is designated as "N" and the other nitrogen is designated as "N", for example, N'-methylureido, N'-ethylureido, N '' 'propylureido, N- methylureide, N-ethylureido, N-propylureido, and the like. "Monofenilureido" refers to a radical of the formula -N (H) -C (0) -N (H) Rh where Rh is a phenyl radical as defined, and the linking nitrogen is designated as "N" and the other nitrogen is designated as "N", for example, N'-phenylureido, N '- (4-nitrophenyl) ureido, N' - (3-chlorophenyl) ureido, and the like. "Monobenzylureide" "refers to a radical of the formula -? (H) -C (0) -? (H) - CH2 - R h where R h is a phenyl radical as defined, and nitrogen union is designated as "N" and the other nitrogen is designated "N" ', for example, N' -benzylureide, N '~ (4-nitrobenzyl) ureido, N' - (3-chlorobenzyl) ureido, and the like. "Monohaloalkylureido" refers to a radical of the formula - (H) -C (0) -? (H) Rf or a radical of the formula -? (R'f) -C (0) -? H2 where R f is a haloalkyl radical as defined and the linking nitrogen is designated as "N" and the other nitrogen is designated "N", eg, N'-chloromethylureide, N '- (2, 2-difluoroethyl) ureido, N '- (3-chloropropyl) ureido, N- (trifluoromethyl) ureido, N- (pentafluoroethyl) ureido, N- (3-iodopropyl) ureido, and the like. "Mono-arylureido" refers to a radical of the formula N (H) -C (0) -N (H) Rb or a radical of the formula -N (Rb) -C (-0) -NH2 wherein Rb is an aryl radical as defined and the binding nitrogen is designated as "N" and the other nitrogen is designated "N", for example, N'- phenylureido, N'- (4-methoxyphenyl) ureido, N '- (3-chlorophenyl) ureido , N-phenylureido, N- (2-trifluoromethyl-phenyl) ureido, N- (4-chlorophenyl) ureido, and the like. "Monoaralkylureido" refers to a radical of the formula - (H) -C (O) -? (H) Rd or a radical of the formula -? (Rd) -C (0) -? H 2 where Rd is an aralkyl adical as defined and the linking nitrogen is designated as "N" and the other nitrogen is designates as "N", for example, N'-benzylureide, N'- (4-methoxybenzyl) ureido, N '- (3-chlorobenzyl) ureido, N-benzylureido, N- (2-trifluoromethylbenzyl) ureido, 'N- (4-chlorobenzyl) ureido, and the like. "(Monoalkyl) (monoaryl) ureido" refers to a radical of the formula -? (Ra) -C (O) -? (Rb) H, or a radical of the formula -? (Rb) -C (O) -? (Ra) H, or a radical of the formula -? (H) -C (O) -? (Ra) (Rb) where Ra is an alkyl radical according to it has been defined and Rb is an aryl radical as defined, and where and the linking nitrogen is designated as "N" and the other nitrogen is designated "N", for example, N-methyl- N'- phenylureido, Nf eni'l-N '-ethylureido, N-methyl-N' - (4-fluorophenyl) ureido, N '-ethyl-N' - (3-cyanophenyl) ureido, and the like. "Monoalkylureidoalkyl" refers to a radical of the formula -Ra-? (H) -C (0) -? (H) Ra or a radical of the formula -Ra-? (Ra) -C (0) -? H 2 where Ra is an alkyl radical as defined and the linking nitrogen is designated as "N" 'and the another nitrogen is designated as "N", for example, N'-methylureidomethyl, 2- (N'-ethylur-edo) ethyl, 1- (N'-propylureido) ethyl, N-methylureidomethyl, 2- (N-ethylureido) ethyl, 1- (N-propylureido) ethyl, and the like. "Monohaloalkylureidoalkyl" refers to a radical of the formula - Ra-? (H) -C (0) -? (H) Rf or a radical of the formula ~ Ra -? (Rf) -C (0) -? H2 'where R a is an alkyl radical as defined and Rf is a haloalkyl radical as defined and the linking nitrogen is designated as "N" and the other nitrogen is designated , as "N" ', eg, N'-chloromethylureidomethyl, 2- (N' - (2, 2-difluoroethyl) ureido) ethyl, 1- (N '- (3-chloropropyl) ureido) ethyl, N - (trifluoromethyl) ureidomethyl, 2- (N- (pentafluoroethyl) ureido) ethyl, 1- (N- (3-iodop.propyl) ureido) ethyl, and the like.

"Monoarylureidoalkyl" refers to a radical of the formula -Ra-N (H) -C (0) -N (H) Rb or a radical of the formula -Ra -N (Rb) -C (0) -NH 2 where Ra is an alkyl radical as defined and Rb is an aryl radical as defined and the linking nitrogen is designated as "N" and the other nitrogen is designated "N", for example, N '- phenylureidomethyl, 2- (N '- (4-methoxyphenyl) ureido) ethyl, 1- (N r- (3-chlorophenyl) ureido) ethyl, N-phenylureidomethyl, 2- (N- (2-trifluoromethylphenyl) ureido) ethyl, 1- (N- (4-chlorophenyl) ureido) ethyl, and the like. "Monoaralkylureidoalkyl" refers to a radical of the formula -Ra -? (H) -C (0) -? (H) Rd or a radical of the formula -Ra-? (Rd) -C (O) -? H2 where R a is an alkyl radical as defined and Rb is an aralkyl radical as defined and the linking nitrogen is designated as "N" and the other nitrogen is designated as "N", e.g., N'-benzylureidomethyl, 2- (N '- (4-methoxybenzyl) ureido) ethyl, 1- (N'- (3-chlorobenzyl) ureido) ethyl, N-benzylureidomethyl, 2- (N- (2-trifluoromethylbenzyl) ureido) ethyl, 1- (N- (4-chlorobenzyl) ureido) ethyl, and the like. "Monophenylamino" refers to an amino radical substituted by a phenyl radical as defined herein.

"Monophenylalkylamino" refers to an amino radical substituted by a phenylalkyl group as defined below for p..ej., Cilamino, 2- (benzyl) butylamino, and the like. "Monophenylaminoalkyl" refers to an alkyl radical as defined substituted by a monophenylamino group as defined, for example, (phenylamino) methyl, 2- (1- (phenyl) ethylamino) ethyl, and the like. "Monophenylalkyalkylalkyl" refers to an alkyl radical as defined substituted by a monophenylalkylamino group as defined, e.g., (benzylamino) methyl, 2- (2-benzyl) butylamino) ethyl, and the like. "Nitro" refers to the radical -N02. "Oxo" refers to the 'substituent = 0. - "optional" or "optionally" means that the circumstances described below may or may not occur, and that the description includes instances in which said event or circumstance occurs and instances in which it does not occur. For example, "optionally substituted aryl" means that the aryl radical may or may not be substituted and that the description includes both substituted aryl radicals and aryl radicals without any substitution. "Phenyl" refers to the benzene radical which is optionally substituted by one or more substituents selected from the group consisting of hydroxy, halo, alkyl, haloalkyl, alkoxy, alkenyl, nitro, cyano, amino, monoalkylamino, dialkylamino, alkylcarbonyl , carboxy, alkoxycarbonyl, and aminocarbonyl. "Phenoxy" refers to the radical of the formula -OR h where Rh is phenyl as defined. "Phenylalkyl" refers to an alkyl radical as defined by a phenyl radical, for example, benzyl, and the like. "Phenylagonyl" refers to an alkenyl radical as defined substituted by a phenyl radical, for example, 3-phenylp'ro? -2-enyl, and the like. "Phenylalkoxy" refers to a radical of the formula - ORi where R 'is a phenylalkyl radical as defined, for example, benzyloxy, and the like. "Phenylalkoxyalkyl" refers to an alkyl radical as defined substituted by a phenylalkoxy radical as defined, for example, benzyloxymethyl, and the like. "Phenylcarbonyl" refers to a radical of the formula -C (0) -Rh where R h is a phenyl radical as defined, for example, (4-chlorophenyl) carbonyl, (4-fluorophenyl) carbonyl, and the like. "Phenylaminocarbonyl" refers to a radical of the formula -C (0) - (H) -R where Rh is a phenyl radical as defined, e.g., (4-chlorophenyl) aminocarbonyl, (4- methoxyphenyl) aminocarbonyl, and the like. "Acceptable counterion for pharmaceutical use" refers to the anions that retain the biology efficacy and the properties of the parent compound that are not undesirable from a biological or biological point of view. of another nature. Examples of such anions can be found in Berge,. YE. et al, Journal of Pharmaceutical Sciences (1977), Vol. 66, No. 1, pp. 1-19. "Acceptable salt for pharmaceutical use" includes acid and basic addition salts. "Acid addition salt acceptable for pharmaceutical use" refers to salts that retain the biological efficacy and properties of free bases, which are not undesirable from a biological or other point of view, and which are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, bromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, and organic acids such as acetic acid, propionic acid, pyruvic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. "Basic addition salt acceptable for pharmaceutical use" refers to salts that retain the biological efficacy and properties of free acids, which are not undesirable from a biological or other point of view. These salts are prepared from the addition of an inorganic base or an organic base to the free acid. Salts derived from inorganic bases include, but are not limited to, the sodium, potassium, lily, ammonium, calcium, magnesium, zinc, aluminum and the like salts. The preferred inorganic salts are those of ammonium, sodium, potassium, calcium and magnesium. Salts derived from organic bases include, without limitation, salts of primary, secondary and tertiary amines, substituted amines including substituted amines existing in nature, cyclic amines and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine , tripropylamine, ethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, trimethamine, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N - ethylpiperidine, polyamine resins and the like. Particularly preferred organic bases are isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline and caffeine. "THF" refers to tetrahydrofuran. "Amount effective in therapeutic terms" refers to the amount of a compound of formula (I) which, when administered to a female human being in need of such administration, is sufficient to effect the treatment, as defined below, of the endometrosis that is relieved by the CCR-1 antagonist activity. The amount of a compound of formula (I) which constitutes an "effective amount in therapeutic terms" will vary according to the compound, the disorder and its severity, and the age of the female human being to be treated, but can be determined in routine by a specialist in the field based on his own knowledge and the present descriptive memory.

"Treat" or "treatment" as used herein refers to the treatment of endometrosis in a female human; and include: (i) preventing disorder in a female human being, in particular, when said female person is predisposed to '' acquire '' but has not yet been diagnosed; (ii) inhibit the disorder, that is, stop its development; or (iii) alleviating the disorder, that is, causing regression of the disorder. "Ureido" refers to a radical of the formula -N (H) -C (0) -NH2. "Ureidoalkyl" refers to a radical of the formula -Ra-.N (H) C (0) NH2 where 'R a is an alkyl radical as defined, for example, ureidomethyl, 2- (ureido) ethyl, - (ureido) propyl, and the like. It is understood from the foregoing definitions and examples that for radicals containing a substituted alkyl group, any substitution may occur on any carbon of the alkyl group of the alkyl group. The compounds of the invention, or their pharmaceutically acceptable salt, can have asymmetric carbon atoms in their structure. The compounds of the invention and their pharmaceutically acceptable salt can therefore exist as simple stereoisomers, racemates, and as "mixtures of enantiomers and diastereomers", said simple stereoisomers, racemates and mixtures thereof being considered within the scope of this invention. The absolute configuration of some carbon atoms within the compounds, if known, is indicated by the appropriate absolute descriptors R or S. The "trans" descriptor is used to indicate that the Rla or Rlb substituents are in the opposite sides of the piperazine plane The "cis" descriptor is used to indicate that the Rla or Rlb substituents are on the same side as the piperazine plane The nomenclature used herein is a modified form of the IUPAC system in which the compounds of the invention are referred to as piperazine derivatives, for example, a compound of formula (la) wherein R6 is -C (O) -, R5 is ethylene, R 4 is -O-, Rla is in the 2-position of the piperazine ring and is ethoxycarbonyl, R 2 is 2- (ethylamino) ethyl in the 4-position of the phenyl ring and R 3 is naphthalene-1-yl substituted in the position 4 by methoxy, that is, the compound of the following formula: Here it is referred to as 1- (2- ((4-methoxynaphthalen-1-yl) oxy) ethyl) carbanyl-2-ethoxycarbonyl-4- (4- (2- (-ethylamino) ethyl) benzyl) piperazine or with the nomenclature according to the following example: 5-chloro-2- [2- [(2R, 5S) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] methyl ester] -2- oxoethoxy] benzoic . Utility and Administration A. Utility The CCR1 antagonists according to the present invention are potent inhibitors of disease incidence in animal models and cell culture models of endometrosis. The compounds of the invention inhibit the migration of monocytes and macrophages induced by chemokines (MlP-la and RANTES) and are therefore useful in the treatment and prevention of endometrosis in women.

Clinical studies were conducted to investigate the benefit of CCRl antagonists according to the present invention in the treatment and prevention of endometrosis. 5 B. Tests Several tests can be used to demonstrate that the compounds inhibit the activity of MlP-la or RANTES-. One trial uses a microphysiometer, which uses a patented silicon-based light-orientable potentiometric sensor to continuously monitor subtle changes in extracellular pH levels. These changes are the result of the generation of acid metabolites excreted by living cells in their immediate microenvironment during basal and stimulus conditions. Previously it had been demonstrated by microphysiometry that THP-1 cells, which have been shown to express the chemokine receptors CCR1 and CCR2, respond by responding to the dose to their respective chemokines, which include MlP-la, RANTES and MCP-1 (a ligand for CCR2). See, e.g., Hirst, M. Et al. , '20"Chemokine receptors", Journal of NIH Research (1995), Vol. 80. Another assay that can be used to demonstrate the ability of the compounds to inhibit the activity of MIP-la and RANTES is based on the measurement of the concentrations, intracellular Ca2 +. and / or increases in intracellular release of [3H] inositol phosphate from cells stimulated by MlP-la and RANTES. The ligands that bind to the CCR1 receptor cause the activation of phospholipase C induced by G protein, which leads to the conversion of phosphate. phosphatidyl inositol to inositol phosphate and diacylglycerol. Inositol phosphate, in turn, binds to a receptor located at intracellular sites that release Ca2 + into the cytoplasm. In addition to increases in Ca + concentration due to release from intracellular deposits, the binding of inasitol phosphate to its receptor produces an increase in extracellular calcium flux through the membrane and into the interior of the cell. Thus, activation of the CCR1 receptor by MlP-la and RANTES and the subsequent inhibition of activation by the compounds of the invention can be determined by assays to look for an increase in the intracellular levels of free Ca2 +. Typically, this can be achieved by using calcium-sensitive fluorescent probes such as quin-2, fura-2 and indo-. Alternatively, functional activation or inhibition of CCR1 receptor activation can be measured by quantification of the [3 H] inositol phosphate release from the cell pre-labeled with [3 H] inositol. Standard in vitro binding assays can be used to demonstrate the affinity of the compounds for the CCR1 receptor (thereby inhibiting the activity of MlP-1α and RANTES by competitive binding to the receptor). See, for example, Neote, K. Et al. , Cell (1993), Vol. 72, pp. 415-425. One assay in particular employs HEK293 cells stably transfected to express the human CCR1 receptor. Cell culture endometrosis models with human U937 cells and primary human periphonal macrophages in combination with a mixture of peritoneal fluid from patients with endometrosis are used as tools to investigate the effects of CCR1 antagonists on inhibition and reduction of the monocyte / macrophage mi- gration induced by chemokine. The determination of the mRNA of CCRl in endometrial and endometriosis tissue sample - can be performed p. ex. by quantitative RT-PCR analysis in real time. Standard in vivo assays that can be used to demonstrate the utility of the compounds in the treatment of endometrosis are eg the animal model of surgically induced endometrosis in intact rats that go through a cycle as also reported in the literature. (fifteen). Other very important models to evaluate the in vivo utility of the compounds in the treatment of endometrosis are the models in primates. In comparison with rodents, primates (Babuino, Cyno olgous, Rhesus monkeys) have a menstrual cycle, reproduce continuously and develop spontaneous endometrosis. In addition, endometrosis can also be indu¬ for example by inoculating menstrual tissue or by autologous endometrial tissue transplantation into the peritoneal cavity (9, 10). It is also possible to isolate and characterize your peritoneal fluid. The experimental data of. the researchers sample For example, non-human primates express the CCR1 receptor. As in human subjects, they could show that the CCR1 is located in the immune cells that infiltrate the tissue in endometriotic lesions / grafts. Using immunohistochemical staining and cell counting, it could be shown that the number of CCRl positive cells is upregulated in Rhesus monkey endmetrotic grafts (see "Figure 6.) The advantage of the non-human primate model is morphology. of endometriotic lesions (red lesions, white lesions, endometrium) that resemble those found in women and reflect the human situation. Studies were conducted in non-human primates to evaluate the activity of the CCR1 antagonist. According to the present invention C. General administration The administration of the compounds of the invention, or their pharmaceutically acceptable salts, in pure form or in an appropriate pharmaceutical composition, can be carried out by any of the modes of administration or administration. agents accepted to serve similar utilities.Therefore, the administration can be, eg, orally, nasal, parenteral, topical, transdermal, or rectal, sublingual, intramuscular, subcutaneous, intravaginal, or intravenous in solid, semisolid, lyophilized, or liquid dosage forms, e.g., tablets, suppositories, pills, gelatin capsules elastic and hard solids, powders, solutions, suspensions, or aerosols, etc., preferably in unit dosage forms suitable for the simple administration of precise dosages. The compositions will include a conventional pharmaceutical carrier or excipient and a compound of the invention as the / an active agent, and, in addition, may include other medicinal agents, pharmaceutical agents, vehicles, adjuvants, etc. In general, depending on the mode of administration desired, the compositions acceptable for pharmaceutical use will contain between about 1% and about 99% by weight of a compound (s) of the invention, or a salt of them acceptable for pharmaceutical use, and between 99% and 1% by weight of one or more appropriate pharmaceutical excipient (s). Preferably, the composition will have between about 5% and 75% by weight of a compound (s) of the invention, or a pharmaceutically acceptable salt thereof, where the remainder are suitable pharmaceutical excipients. The preferred route of administration is oral, using a convenient daily dosage regimen that can be adjusted according to the degree of severity of the disease state to be treated. For such oral administration, a pharmaceutically acceptable composition containing a compound (s) of the invention, or a pharmaceutically acceptable salt thereof, is formed by the incorporation of any of the excipients that are normally employed. . Said excipients include fillers, binders, disintegrants, buffer solutions, preservatives, antioxidants, lubricants, flavors, thickeners, coloring agents, emulsifiers, etc., non-toxic and chemically compatible, eg. , the pharmaceutical grades of mannitol, lactose, starch, pregelatinized starch, magnesium stearate, sodium saccharin, talcum, cellulose ether derivatives, glucose, gelatin, sucrose, citrate, cyclodextrin, propyl gallate, and so on. Said compositions take the form of solutions, suspensions, tablets, pills, capsules, powders, sustained-release formulations, etc. Preferably, said compositions will take the form of a capsule, caplet or tablet and therefore will also contain a diluent such as, for example, lactose, sucrose, dicalcium phosphate, etc.; a disintegrant such as, for example, croscarmellose sodium or derivatives thereof; a lubricant such as, for example, magnesium stearate, etc.; and a binder such as, for example, a starch, acacia gum, polyvinyl pyrrolidone, gelatin, cellulose ether derivatives, etc. The compounds of the invention or their pharmaceutically acceptable salts can also be formulated in a suppository using, for example, between about 0.5% and about 50% active ingredient disposed in a vehicle that slowly dissolves within the body. , for example, polyoxyethylene glycols and polyethylene glycols (PEG), p. ex. , PEG 1000 (96%) and PEG 4000 (4%), and propylene glycol. Liquid compositions for administration in pharmaceutical use can be prepared, for example, by dissolving, dispersing, etc., a compound (s) of the invention (between about 0.5% and about 20%), or a salt thereof. they are acceptable for pharmaceutical use, and optional pharmaceutical adjuvants in a vehicle, such as, for example, water, saline, aqueous dextrose, aqueous cyclodextrin, glycerol, ethanol etc., to form a solution or suspension. If desired, a pharmaceutical composition of the invention may also contain minor amounts of auxiliary substances such as, for example, wetting or emulsifying agents, pH buffering agents, antioxidants, etc., such as, for example, citric acid, monolaurate. of sorbitan, triethanolamine oleate, butylated hydroxytoluene, etc. The methods that are employed in effect to prepare such dosage forms are known, or will be apparent, to those skilled in the art; eg, see Re-mington's Pharmaceutical Sciences, 18th Ed., (Mack Publishing Company, Easton, Pennsylvania, 1990). In any case, the composition to be administered will contain an effective amount for therapeutic use of a compound of the invention, or a salt thereof acceptable for pharmaceutical use, for the treatment of edometry relieved by the inhibition of the activity. of the chemokines, MlP-la and RANTES. The . compounds of the invention, or their pharmaceutically acceptable salts, are administered in an effective amount for therapeutic use which will vary depending on a variety of factors including the activity of the specific compound that is employed, the metabolic stability and length of action of the compound, age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, severity of disease states in particular, and of the host undergoing therapy. In general, an effective daily dose for therapeutic use is between about 0.014 mg and about 14.0 mg / kg of body weight per day of a compound of the invention, or a salt thereof acceptable for pharmaceutical use; preferably, between about 0.14 mg and about 10.0 mg / kg of body weight per day; and even more preferably, between about 1.4 mg and about 7.0 mg / kg of body weight per day.

For example, to administer to a 70kg person, the dosage range would be between about 1.0 mg and about 1.0 gram per day of a compound of the invention, or a pharmaceutically acceptable salt thereof, preferably between about 10 mg and about 70 mg per day, and even more preferably between about 100 mg and about 500 mg per day. PREFERRED EMBODIMENTS One aspect of the invention are compounds of formula (la) as defined in the summary of the invention of these compounds, a preferred group of compounds of formula (la) is the group of compounds wherein: R3 is a carbocyclic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxy- alkylsulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, ariisulfonilo, alkylthioalkyl, alkylsulfinylalkyl, alkyl alquilsulfonil- , alkoxy, hydroxyalkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, aminoalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy) cycloalkylalkyl, cycloalkylamino, ci- • cloalquilaminoalquilo, -cianoalquilo, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy) aralkyl, (monoalkylamino) aralkyl, (hydroxyalkyl) hyalo yl, hydroxyalkenyl, hydroxyalkyl alkynyl, alkoxyalkyl, (alkoxy) aralkyl, aryloxyalkyl, aralkoxyalkyl, amino, monoalkylamino, dialkylamino, monoarylamino, .monoaralquilarrd.no, aminoalquilami- not, heterocyclylamino, (cycloalkylalkyl) amino, alkylcarbonylamino, alkoxycarbonylamino, not alquenilcarbonilami- , cycloalkylcarbonylamino.no, arylcarbonylamino, heterocyclylcarbonylamino, haloalkylcarbonylaryl, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbonyl). (Alkyl) amino, (alkoxycarbonyl) (alkyl) amino, alkylsulfonylamino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, hydroxyalkyl guilaminoalguilo, monoarilaminoalquilo, monoaralquilaminoalquilo, alkylcarbonylaminoalkyl, alkylaminoalkyl arilcarbonilami-, (alkylcarbonyl) (alkyl) aminoalkyl, (ci- cloalquialquil) aminoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylalkylcarbonylaminoalkyl, (alkoxycarbonyl) (alkyl) aminoalkyl, alkylsulphorylaminoalkyl, (alkylsulfonyl) (alkyl) aminoalkyl, arylsulfonylaminoalkyl, (arylsulfonyl) (alkyl) aminoalkyl, heterocyclylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, bonilo aralquiicar-, (hydroxyalkoxy) carbonyl, carboxyalkyl, alkoxycarbonylalkyl, ara'lcoxicarbonilalquilo, quilcarboniloxialquilo alkoxyalkyl, dialquilaminocarboniloxíalquilo, alkylcarbonylalkyl, arylcarbonylalkyl, bonilalquilo aralquilcar-, aminocarbonyl, monoalkylaminocarbonyl, dialquilaminoc arbonyl, monoarylaminocarbonyl, monoalkylaminocarbonyl, (aminocarbonylalkyl) aminocarbonyl, (monoalkylaminocarbonylalkyl) aminocarbonyl, (carboxyalkyl) aminocarbonyl, (alkoxycarbonylalkyl) aminocarbonyl, (aminoalkyl) aminocarbonyl, (hydroxyalkyl) aminocarbonyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl- alkyl, monoarylaminocarbonylalkyl, monoaralkylaminocarbonylalkyl, -amidino, hydroxyamidino, guanidino, ureido, monoalkyluride, monoarylureido, monoaralkylureido, monohaloalkylureido, (monoalkyl) (mo-no-aryl) ureido, dialkylureido, diarylureido, (haloalkyl-carbonyl) ureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl) (alkyl) ureidoalkyl, (alkoxycarbonylalkyl) ureidoalkyl, glycinamide, monoalkylglycinamido, aminocarbonylglycinamido, (alkoxyalkylcarbonyl) glycinamide, (aminocarbonyl) (alkyl) g licinamido, (alkoxycarbonylalkylcarbonyl) (alkyl) glycinamide, (alkoxycarbonylaminoalkylcarbonyl) glycinamide, arylcarbonylglycinamide, (arylcarbonyl) (alkyl) glycinamide, (monoaralkylaminocarbonyl) glycinamide, (monoaralkylaminocarbonyl) (alkyl) glycinamide, (monoarylaminocarbonyl) glycinamide, (monoarylaminocarbonyl) (alkyl) glycinamide, glycinamidoalkyl, alaninamido, monoalkylalaninamide, alaninamidoalkyl , heterocyclyl and heterocyclylalkyl. Of this group of compounds, a preferred subgroup of compounds is the group of compounds wherein: R 4 is -O-, -N (R 7) - or -C (R 8) -, - R 5 is - - - -. . an alkylene chain; R7 is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl; and each R8 is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, hydroxy, alkoxy, hydroxyalkyl, alkoxyalkyl, amino, monoalkylamino, dialkylamino, alkylcarbonylamino, cycloalkylcarbonylamino, cycloalkylalkylcarbonylamino, alkoxycarbonylamino, alkylsulfonylamino, arylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbaryl) (alkyl) amino, aralkylcarbonylamino, (aralkylcarbonyl) (alkyl) amino, alkylcarbonylaminoalkyl, cycloalkylcarbonylaminoalkyl, alkoxycarbonylaminoalkyl, (alkylcarbonyl) (alkyl) aminoalkyl, aralkylcarbonylaminoalkyl, heterocycliccarbonylaminoalkyl, (aralkylcarbonyl ) (alkyl) aminoalkyl, arylsulfonylamino, alkylsulphonylaminoalkyl, ureido, monoalkylureido, monohaloalkylureido ,. .dialquilureido. ureidoalkyl, monoalkylureidoalkyl, dialkyl ureidoalkyl, monohaloalkylureidoalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, and dialkylaminocarbonylalkyl. From this subgroup of compounds, a preferred class of compounds is the group of compounds wherein: R * is -O-; R 5 is methylene; and R 6 is -C (0) -. Of this class of compounds, a preferred subclass of compounds is that group of compounds wherein: Rla is one 'or more substituents selected from the group consisting of halo, alkyl, cycloalkyl, alkylaminoalkyl cicloalquilami-, haloalkyl, hydroxyalkyl, hidroxia.lqueni- so, hydroxyalkynyl, (hydroxy) aralkyl, cyanoalkyl, haloalquilcarbonilaminoalquilo, alkoxyalkyl, aralkyl coxialquilo, alkylthioalkyl, hydroxyalkylthioalkyl, aminoalkyl, -monoalquilaminoalquilo, dialkylaminoalkyl, monoarilaminoalquilo, monoaralquilaminoalquilo, azidoalkyl, monoalquilureidoalquilo, (lalquil alcoxicarboni-) ureidoalkyl, hydroxyalkylaminoalkyl, ari- loxialquilcarboniloxialquilo , Aralkoxyalkylcarbonyloxyalkyl, alkylcarbonylalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, and heterocyclylalkyl; R2 is one or more substituents selected from the group consisting of hydrogen and halo; is phenyl which is optionally substituted by one or more sub- tituyentes selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, aminoalkoxy, cycloalkyl, cycloalkylaminoalkyl, aralkyl, hydroxyalkyl, ( monoalkylamino) aralkyl, alcoxialqui- it, amino, monoalkylamino, dialkylamino, monoaralqui-lamino, alkylcarbonylamino, alkenylcarbonylamino, ci-cloalquilcarbonilaird.no, arylcarbonylamino, heterocyclic-carbonylamino, haloalquilcarbonilarrd.no, alcoxialquilcar-bonilamino, alcoxicarbonilalquilcarbonilamino, (alkyl-carbonyl) ( alkyl) amino, alkylsulfonylamino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, monoarylaminoalkyl, monoaralkylaminoalkyl, alkylcarbo-nylaminoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl) (alkyl) aminoalkyl, (cycloalkyalkyl) aminoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylalkylcarbonylaminoalkyl, (alkoxycarbonyl) (alkyl) aminoalkyl ilo, alkylsulfonylaminoalkyl, (alkylsulfonyl) (alkyl) aminoalkyl, arylsulfonylaminoalkyl, (arylsulfonyl) (alkyl) minoalkyl, heterocyclylaminoalkyl, carboxy, alkoxycarbonyl, alkylcarbonyl, (hydroxyalkoxy) carbonyl, aminocarbonyl, monoalkylaminocarbonyl, monoarylaminocarbonyl, (aminocarbonylalkyl) .aminocarbonilo, (aminoalkyl) aminocarbonyl, (hydroxyalkyl) aminocarbonyl, chyle dialquilaminocarbonilal-, hydroxyamidino, ureido, monoalquilureido, monoammonium rilureido,. monoaralkylureide, (monoalkyl) (monoaryl) ureido, (haloalkylcarbonyl) ureido, ureidoalkyl, monoalkylureidoalkyl, dialkyl ureidoalkyl, monoalkyureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl) (alkyl) ureidoalkyl, (alkoxycarbonylalkyl) ureidoalkyl, glycinamide, noalkylglycinamido, aminocarbonylglycinamide, (al-coxyalkylcarbonyl) glycinamide, (aminocarbonyl) (alkyl) glycinamide, (alkoxycarbonylalkylcarbo-nyl) (alkyl) glycinamide, (alkoxycarbonylaminoalguylcarbonyl) glycinamide, arylcarbonylglycinamide, (arylcarbo-nyl) (alkyl) glycinamide, (monoaralkylaminocarbonyl) ) glycinamido, (monoaralquilaminocarbonil) (alkyl) glycinamido, (monoarilaminocarbonil) glycinamido (monoarilaminocarbonil) (alkyl) glycinamido, alaninamido, heterocyclyl and heterociclilalguilo.

Preferred compounds within this subclass of compounds -of are selected from the group consisting of the following compounds: (25) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluoro- benzyl) piperazine; 1- ((phenoxy) methyl) carbonyl-2-ethyl-4- (4-fluorobenzyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-ethylpiperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (methoxymethyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- ((acetylamino) methyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-2- (2- ((4-fluorobenzyl) amino) ethyl) 4- (4-fluorobenzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-2- (2- ((methyl) amino) ethyl) -4- (4-fluorobenzyl) piperazine; 1- ((4-chlorophenoxy) ethyl) carbonyl-2- (2- ((2-hydroxyethyl) amino) ethyl) -4- (4-fluorobenzyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (((((4-chlorophenoxy) methyl) carbonyl) oxy) methyl-5-methylpiperazine; 4- (4-fluorobenzyl) -l- ((4-chlorophenoxy) methyl) carbonyl-3- (ethoxycarbonyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (methoxycarbonyl) methylpiperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- ((methoxy) methyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2- (methoxy) ethyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxy-2- (4-methylphenyl) ethyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxypropyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxybut-4-ynyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-5- (2-hydroxy-2-methylpropyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxyethyl) piperazine; - ((4-chlorophenoxy) methyl) carbonyl-3- (2- ((2-hydroxyethyl) amino) ethyl) -4- (4-fluorobenzyl) piperazine; (cis) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2,3-dimethylpiperazine; (25, 5R) -1- ((4-chloro-3,5-dimethoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluoxobenzyl) piperazine; (2S, 5S) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2,5-dimethylpiperazine; (2R, 55) -4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbbonyl-2-methyl-5- (2-methylthio) ethylpiperazine; '5 (2R, 5R) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5- (benzyloxy) methylpiperazine; • (2R, 5R) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- (((2-hydroxyethyl) thio) methyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (N '-10 (ethoxycarbonylmethyl) ureido) methyl) piperazine; (2R, 55) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5- ((amino) carbonyloxy) methyl-4- (4-fluorobenzyl) iperazine; '- 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3-; ((acetyl) methyl) piperazine; 5 (2R, 5R) -4- (4-fiorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5- (1-hydroxy-1- (phenyl) methyl) piperazine; (2R, 5R) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5- (1-hydroxybutyl) piperazine; (2R, 55) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-0-fluorobenzyl) -5- ((diethylamino) methyl) iperazine; (2R, 55) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((dimethylamino) methyl) piperazine; (2R, 55) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluo-robenzyl) -5- (((cyclopropyl) amino) methyl) piperazine; (2R, 55) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluoro-benzyl) -5- ((morpholin-4-yl) methyl) piperazine; (2R, 5R) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((piperazin-1-yl) methyl) piperazine; (cis) -1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-2,6-dimethyl-4- (4-fluorobenzyl) piperazine; (cis) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2,6-dimethylpiperazine; 1- ((phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; 1- ((2- (acetylamino) phenoxy) methyl) carbonyl-2-methyl-4 ~ (4-fluorobenzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-2- (2-hydroxypropyl) -4- (4-fluorobenzyl) piperazine; - ((4-chlorophenoxy) methyl) carboni.1-2- (2-hydroxybut-3-enyl) -4- (4-fluorobenzyl) piperazine; - ((4-chlorophenoxy) methyl) carbonyl-3-trifluoromethyl-4- (4-fluorobenzyl) piperazine; and (trans) -1- ((4-chloro-2- ((4- (2,5-di (trifluoromethyl) phenylcarbonyl) piperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2, 5- dimethyl-4- (4-fluorobenzyl) piperazine. Of this subclass of compounds, a preferred group of compounds is the group of compounds wherein: Rla is one or more substituents selected from the group consisting of alkyl, cycloalkyl, hydroxyalkyl, hydroxyalkenyl, cyanoalkyl, alkoxyalkyl, monoalkylaminoalkyl , azidoalkyl, monoalkylureidoalkyl aryloxyalkylcarbonyloxyalkyl, and heterocyclylalkyl; R 2 is one or more substituents selected from the group consisting of hydrogen, chloro or fluoro; R 3 is phenyl substituted by one or more substituents selected from the group consisting of hydroxy, halo, alkyl, alkoxy, formyl, nitro, cyano, aminoalkoxy, cycloalkylaminoalkyl, hydroxyalkyl, (monoalkylamino) aralkyl,. .alcoxyalkyl., amino ,. monoalkylamino, dialkylamino, monoaralquilamino, alkylcarbonylamino, alquenilcarbonilarrd.no, cicloalquilcarboniland.no, arylcarbonylamino, heterocyclylcarbonylamino, bonilámino haloalquilcar--, alkoxyalkylcarbonylamino, quilcarbonilamino alcoxicarbonilal-, alkylsulfonylamino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, monoaralquilaminoalquilo, alkylcarbonylaminoalkyl, carbonylaminoalkyl aryl-, (alkylcarbonyl) (alkyl) aminoalkyl, (cycloalkyalkyl) aminoalkyl alkoxycarbonylalkylcarbonylaminoalkyl, alkylsulphonylaminoalkyl, (alkylsulfonyl) (alkyl) aminoalkyl, arylsulfonynyalkyl, (arylsulfonyl) (alkyl) aminoalkyl, carboxy, alkoxycarbonyl, alkylcarbonyl, (hydroxyalkoxy) carbonyl, aminocarbonyl, monoalkylaminocarbonyl , monoarylaminocarbonyl, (aminocarbonylalkyl) aminocarbonyl, (aminoalkyl) aminocarbonyl, (hydroxyalkyl) aminocarbonyl, hydroxyamidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, (monoalkyl) (monoaryl) ureido, (haloalkylcarbonyl) ureido, ureidoalkyl, monoalkyl-reidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl , monoaralkylureidoalkyl, monohaloalkylurei-doalkyl, (ha-loalkyl) (alkyl) ureidoalkyl, (alkoxycarbonylalkyl) ureidoalkyl, glycinamide, monoalkyl glycinamide, aminocarbonylglycinamido, (alkoxyalkylcarbonyl) glycinamide, (aminocarbonyl) (alkyl) glycinamide, (alkoxycarbonylalguylcarbonyl) (alkyl) glycinamide, (al-coxycarbonylaminoalkylcarbonyl) glycinamide, arylcarbo-nilglycinamido, (arylcarbonyl) (alkyl) glycinamide, (monoaralkylaminocarbonyl) (alkyl) glycinamide, (monoalkylaminocarbonyl) glycinamide, - (monoarylaminocarbonyl) (alkyl) glycinamide, alaninamide, heterocyclyl and heterocyclylalkyl. Preferred compounds within this group of compounds in this subclass group of compounds are selected from the group consisting of the following compounds: 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-2-methyl-4 - (4- fluorobenzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-ethylpiperazine; (2R) -4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-propylpiperazine; (2S) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) -methyl) carbonyl-2-propyl-piperazine; - (4-fluorobenzyl) -1- (((4-chlorophenoxy) methyl) carbonyl) .spiro [cyclopropan-1,2'-piperazine]; - ((4-chlorophenoxy) methyl) carbonyl-2-hydroxymethyl-4- (4-fluorobenzyl) piperazine; - (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (2- (methoxy) ethyl) piperazine; - ((4-chlorophenoxy) methyl) carbonyl-2- (2- ((2-methylpropap) amino) ethyl) -4- (4-fluorobenzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-3-methyl-4- (4-fluorobenethyl) piperazine; 1- ((4-chlorophenoxy) ethyl) carbonyl-4- (4-fluorobenzyl) -5-methylpiperazine; (2R) -1- ((4-chlorophenoxy) methyl) carbonyl-3-methyl-4- (4-fluorobenzyl) piperazine; (2S) -1- ((4-chlorophenoxy) ethyl) carbonyl-3-methyl-4- (4-fluorobenzyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (hydroxymethyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxyethyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) -methyl) carbonyl-2- (((methyl) ureido) methyl) piperazine; (2R, 3R) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2,3-dimethylpiperazine; (cis) -1- ((4-chlorophenoxy) methyl) carbonyl-3,5-dimethyl-4- (4-fluorobenzyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (2- (((4-chlorophenoxy) methyl) carbonyl) oxy) ethyl-5-methylpiperazine; (2R, 5R) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((hydroxy) methyl) piperazine; (2R, 5R) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5- ((methoxy) methyl) piperazine; (2, 55) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5- (1-methylethyl) piperazine; (2R, 5R) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5- (1-hydroxyethyl) piperazine; (2R, 5R) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5- (1-hydroxyprop-3-enyl) piper.azine; (2R, 55) -l- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((cyano) methyl) piperazine; (2R, 5R) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((1,2,4-triazol-2-yl) methyl) piperazine; (2R, 5R) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((tetrazolyl) methyl) piperazine; (35, 55) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3,5-dimethylpiperazine; 1- ((4-chloro-3-nitrophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (diethylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2-hydroxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((5-chloro-2-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((ethyl) (1-methylbutyl) aminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; 1- ((4-chloro-2-aminophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; 1- ((4-cyclo-3-nitrophenoxy) methyl) carbonyl-2-methyl-4 - (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (benzylamino) phenoxy) methyl) carbonyl-2, -dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((4-chloro-2- ((1-methylbutyl) amino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2 ~ (isopropylcarbonylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((4-chloro-2- (N '- (2,4-dichlorophenyl) ureido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N'- (4-nitrophenyl) ureido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N '- (4-methylphenyl) ureido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N '-benzylureido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((cyclopropylmethyl) aminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazole; (trans) -1- ((4-chloro-2- (phenylaminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (acetylaminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; _ (trans) -1- ((4-chloro-2- ((methylamino) (phenyl) methyl) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (1- (phenylsulfonyl) (methyl) aminoethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (1- (acetyl) (methyl) aminoethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (1- (N-methyl-N'-ethylureido) ethyl) phenoxy) methyl) carbhenyl-2,5-dimethyl-4- (4-fluorobenzyl) pipera- zina; (trans) -1- ((4-chloro-2- (1- ((methyl) (ethyl) amino) ethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (1- (dimethylamino) ethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (2R) -1- ((4-chloro-2- ((4-t-butoxycarbonylpiperazin-1-yl) methyl) phenoxy) methyl) 'carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((piperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (oxazol-2-ylaminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; 1- ((4-chloro-2- (morpholin-4-ylmethyl) phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-bromo-2-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-fluoro-3-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; 1- ((4-chloro-2-methoxycarbonylphenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2-methoxycarbonylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; 1- ((4-chloro-2-aminocarbonylphenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2-carboxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2-formylphenoxy) methyl) carbonyl-2, 5'-dimethyl-4- (4-fluorobenzyl) piperazine; (rans) -1- ((4-chloro-2-cyanophenoxy) 'methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-cyanophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-methyl-2-aminophenoxy) metyr) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-methyl-2-acetylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxycarbonylphenoxy) methyl) carbonyl-2,5- dimethyl-4- (4-fluorobenzyl) piperazine: (trans) -1- ((3-nitrophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-acetyl-2- (aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-nitro-3-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((5-nitro-2-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-amino-3-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((5-nitro-2-aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-aminophenoxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-methoxy-2-acetylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((5- methoxy-2-acetylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- ((2-hydroxyethyl) aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- ((2-hydroxyethoxy) carbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; - (trans) -1- ((2 ^ (2-hydroxyethoxy) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) pip-erazine; (trans) -1- ((2-Acetyl-4,5-dimethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((5-methoxy-2- (methoxycarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; - (4- fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (N '-methylureido) amino) methyl) piperazine; (trans) -1- ((4-methyl-2-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-chloro-5-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-5-ritrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (hydroxymethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-2- (2-azidoethyl) -4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (phthalimido) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluoro-benzyl) piperazine; (trans) -1- ((4-chloro-2- (maleimido) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1-. { (4-chloro-2- ((4- (benzylcarbonyl) piperazin-1-yl) methyl) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((4- ((2,3-, 4-trifluorophenyl) aminocarbonyl) piperazin-1-yl) methyl) phenoxy) methy) carbonyl-2, 5-dimethyl- 4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((4- ((2-fluorophenyl) aminocarbonyl) piperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4 - fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((N '- (2-, β-difluorophenyl) ureido) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (ethenylcarbonylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (cyclopropylcarboniland.no) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (cyclopentylcarbonylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (rans) -1- ((4-chloro-2- ((furan-2-yl) carbonylamino) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (phenylcarbonylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((N '- (3-methoxyphenyl) ureido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; trans) -1- ((4-chloro-2- ((N '- (methoxycarbonylmethylcarbonyl) - N' - (methyl) glycinamide) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((Nr- (2-methoxycarbonylethyl) carbonyl- N '- (methyl) glycinamide) pheno? i) methyl) carbonyl-2, 5- dimethyl-4- (4- "fluorobenzyl) piperazine; - (trans) -1- ((4-chloro-2- ((N '- (3-methylbenzyl) aminocarbonyl- N' - (methyl) glycinamide) phenoxy) methyl) carbonyl-2 , 5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((N '- (3-trifluoromethyl-4-fluorophenyl) carbonyl-N'- ("methyl) ) glycinamide) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-cloxo-2- ((N'- (4-methylbenzyl) aminocarbonyl- N '- (methyl) glycinamide) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((N' - (3-chlorof enyl) carbonyl-N'- (methyl) glycinamide) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; - (trans) -1- ((4-chloro-2) - ((N'- (4-fluorobenzyl) aminocarbonyl- N '- (methyl) glycinamide) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N '- (2-iodophenylcarbonyl) glycinamide) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (Nr- (2,3-difluorophenylcarbonyl) glycineamido) phenoxy) "- methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N '- ((4-phenoxyphenyl) aminocarbonyl) glycinamide) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; - '(trans) -1- ((4-chloro-2- (N' - (2,4-diflurophenylcarbonyl) glycinamide) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((2-iodophenylcarbonyl) aminomethyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) - 1- ((4-Chloro-2- ((ethoxycarbonylmethylcarbonyl) aminomethyl) phenoxy) -methyl) carbonyl-2-, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro -2- (N '- (3-chloropropyl) ureidomethyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2) - (N '- (2-fluoro-6 ~ trifluoromethylphenyl) ureidomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piper azine; (trans) -1- ((4-chloro-2- ((3-fluorophenyl) carbonylaminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N '- (2- (ethoxycarbonyl) ethyl) ureidomethyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) cyl) piperazine; (25) -1- ((4-chloro-2- (ureido) phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((2,5-di (trifluoromethyl) phenyl) carbonylaminomethyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; and (trans) -1- ((4-chloro-2- '(N' - (2- (phenyl) cyclopropyl) ureidoethyl) phenoxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) ) piperazine. A more preferred group of compounds in this subclass group of compounds are the compounds wherein: Rla is one or more substituents - selected from the group consisting of alkyl and hydroxyalkyl; R2 is one or more substituents selected from the group consisting of hydrogen, chloro or fluoro; R 3 is phenylene substituted by one or more substituents selected from the group consisting of halo, alkyl, alkoxy, formyl, nitro, cycloalkylaminoalkyl, hydroxyalkyl, amino, alkylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarboniland.no, alkoxycarbonylalkylcarbonylamino, alkylsulfonylamino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, (alkylsulfonyl) (alkyl) aminoalkyl, alkylcarbonyl, aminocarbonyl, o-alkylaminocarbonyl, monoarylaminocarbonyl, (aminocarbonylalkyl) aminocarbonyl, (aminoalkyl) aminocarbonyl, hydroxyamidino,. ureido, (haloalkylcarbonyl) ureido ', ureidoalkyl, glycinamide, monoalkylglycinamido, aminocarbonylglycinamide, (alkoxyalguylcarbonyl) glycinamide, (aminocarbonyl) (alkyl) glycinamide, (alkoxycarbonylaminoalkylcarbonyl) glycinamide, alaninamide, and heterocyclylalkyl. Preferred compounds within this most preferred group of compounds in this subclass group of compounds are selected from the group consisting of the following compounds: (trans) -1- ((4-chloro-3-nitrophenoxy) methyl) carbonyl-2y-5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (hydroxymethyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (2R, 55) -1- ((4-Chloro-2- (aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (2 5, 5R) -l - ((4-bromo-3,5-dimethoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (2R, 55) -1- ((3-hydroxy-5-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (25, 5R) -1- ((4-nitro-3-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (2R) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (2-hydroxyethyl) piperazine; (trans) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonane-2,5-dimethylpiperazine; (2R, 55) -4- (4-Fluorobenzyl ') -1- ((4-chlorophenoxy) methyl) carbonyl-2,5-dimethylpiperazine; (trans) -1- ((4-chloro-3,5-dimethoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (2R, 55) -1- ((4-chloro-3,5-dimethoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (2R, 55) -4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (2-hydroxyethyl) -5-methylpiperazine; (2R, 6R) -A- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2, β-dimethylpiperazine; (trans) -1- ((4-chloro-2-methoxyphenyl) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; 1- ((4-chloro-2- (hydroxymethyl) phenoxy) methyl) carbonyl-2-methyl-4- (4-fluoro-encyl) piperazine; (2R, 55) -1- ((4-chloro-3- (hydroxymethyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (1-hydroxyethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-Chloro-2- (aminomethyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (ureidomethyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2-aminophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; 1- ((4-chloro-2- (acetylamino) phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; '(trans) -4- (4-fluorobenzyl) -1- ((2-acetylamino-4-chlorophenoxy) methyl) carbonyl-2,5-dimethylpiperazine; (trans) -1- ((4-chloro-2- (propylcarbonylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (methoxymethylcarbonylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (2- (methoxycarbonyl) ethylcarbonylamino) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (2- (ethoxycarbonyl) ethylcarbonylane) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (methylsulfonylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (bromomethylcarbonylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (2R) -1- ((4-chloro-2- (glycinamide) phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((N '-methylglycinamido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (alaninamido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((aminocarbonyl) glycine-mido) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((aminocarbonyl) (methyl) glycine) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N'-ethylurio) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (ethylcarbonylamino) phenoxy) methyl) carbonane-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2-amino-5-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl ') piperazine, dihydrochloride salt; (trans) -1- ((4-chloro-2- (((ethyl) amino) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (((diethyl) amino) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (((cyclopropyl) amino) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (((dimethyl) amino) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (((methyl) amino) ethyl) phenoxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((amino) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((4-methylpiperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((piperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (ethylaminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (1- (methylamino) ethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2 - (l- (methylsulfonyl) (methyl) aminoethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (2R) -1- ((4-chloro-2- ((piperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (2i?, 5 .5) -1- ((4-chloro-2- ((piperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((4-t-butoxycarbonylpiperazin-1-yl) methyl) phenoxy) methyl ') carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (imidazol-1-ylmethyl) phenoxy) methyl) car-. bonyl-2, 5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (1- (imidazol-1-yl) ethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (triazol-1-ylmethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (tetrazol-1-ylmethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((morpholin-4-yl) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (2R) -1- ((4-Chloro-2-aminocarbonylphenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; 1- ((4-chloro-2-formylphenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (2R, 55) -1- ((4-chloro-2-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (2R) -1- ((4-chloro-2-formylphenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (methylaminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- '((aminocarbonylmethyl) aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((4-chloro-2- ((2-aminoethyl) aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((4-aminocarbonylphenyl) aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (hydroxyamidino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2-acetylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (-aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((N '- (trichloromethylcarbonyl) ureido) phenoxy) methyl) carbonyl-2, 5-dimethyl-1-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N '- (methoxymethylcarbonyl) glycinamide) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; and (trans) -l- ((4-chloro-2- (N '- (ethoxycarbonylaminocarbonyl) glycinamide) phenoxy) methy) carbonyl-2,5- dimethyl-4- (4-fluorobenzyl) piperazine The group Most preferred compounds within this subclass group of compounds are the compounds wherein R 2 is 4-fluoro and R 3 is phenyl substituted at the 4-position with chlorine and at the 2-position by aminocarbonyl, ureido, or glycinamide; that is, the compounds selected from the group consisting of the following compounds: - (2R, 55) -1- ((4-Chloro-2- (aminocarbonyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- ( 4- fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (glycinamide) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (2R) -1- ((4-chloro-2- (ureido) phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((4-chloro-2- (ureido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (2R, 55) -1- ((4-chloro-2- (ureido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; and (2R, 55) -1- ((4-chloro-2- (glycinamide) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine. Of the preceding subgroup of compounds, another preferred class of compounds are the compounds wherein: R4 is -N (R7) -; R5 is methylene; R6 is -C (O) -; and R7 is selected from the group consisting of hydrogen, alkenyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl. Of this class of compounds, a preferred subclass of compounds are compounds wherein: Rla is one or more substituents selected from the group consisting of halo, alkenyl, cycloalkyl, cycloalkylaminoalkyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy) aralkyl, cyanoalkyl, haloalkylcarbonylaminoalkyl, alkoxyalkyl, aralkoxyalkyl, alkylthioalkyl, hydroxyalkylthioalkyl, aminoalkyl, onoalkylaminoalkyl, dialkylaminoalkyl, monoarylaminoalkyl, monoaralkylaminoalkyl, azidoalkyl, monoalkylureidoalkyl, (alkoxycarbonylalkyl) ureidoalkyl, -hydroxyalkylaminoalkyl,. aryloxyalkylcarbonyloxyalkyl, aralkoxyalkylcarbonyloxyalkyl, alkylcarbonylalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, and heterocyclylalkyl; "R 2 is one or more substituents selected from the group consisting of hydrogen and halo; R3 is phenyl which is ppcionalmente substituted by one or more substituents selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, aminoalkoxy, cycloalkyl, cycloalkylaminoalkyl, aralkyl, - hydroxyalkyl, ( monoalkylamino) aralkyl, alkoxyalkyl, amino, monoalkylamino. dialkylamino, monoaralqui- lamino, alkylcarbonylamino, alquenilcarboniland.no, ci- cloalquilcarboniland.no, arylcarbonylamino, heterocyclyl- carbonylamino, haloalkylcarbonylamino, bonilamino alcoxialquilcar-, alcoxicarbonilalquilcarbonilamino, (alkylcarbonyl) (alkyl) amino, alkylsulfonylamino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, monoammonium rilaminoalquilo, monoaralquilaminoalquilo, nilaminoalquilo alquilcarbo-, arylcarbonylaminoalkyl, (alquilcarb¿ _ ^ _. nil) (alkyl) aminoalkyl, (cicloalquialquil) aminoalkyl, alkoxycarbonylaminoalkyl, alcoxicarbonilalquilcarbonilaminoalquilo, (alcoxicarbo- 'nil) ( alq uil) aminoalkyl, alkylsulfonylaminoalkyl, (alkylsulfonyl) (alkyl) aminoalkyl, arylsulfonylaminoalkyl, (arylsulfonyl) (alkyl) aminoalkyl, heterocyclylaminoalkyl, carboxy, alkoxycarbonyl, alkylcarbonyl, (hydroxyalkoxy) carbonyl, aminocarbonyl, monoalkylaminocarbonyl, monoarylaminocarbonyl, ( aminocarbonylalkyl) aminocarbonyl, (aminoalkyl) aminocarbonyl, (hydroxyalkyl) aminocarbonyl, chyle dialquilaminocarbonilal-, Hydroxyamidino, ureido, monoalquilureido, monoammonium rilureido, monoaralquilureido, (monoalkyl) (monoaryl) ureido, (haloalquilcarbonil) ureido, ureidoalkyl, monoalquilureidoalquilo, dialquilureidoalquilo, monoari- lureidoalquilo, -monoaralquilureidoalquilo, monohaloal- quiiureidoalquilo, (haloalkyl) (alkyl) ureidoalkyl (alkoxycarbonylalkyl) ureidoalkyl, glycinamide, monoalkylglycinamido, aminocarbonylglycinamide, (alkoxyalkylcarbonyl) glycinamide, (-aminocarbonyl) (alkyl) glycinamide, - (alkoxycarbonylalkylcarbonyl) (alkyl) glycinamide, (alkoxycarbonylaminoalguylcarbonyl) glycinamide , arylcarbonylglycinamide, (arylcarbonyl) (alkyl) glycinamide, (monoaralkylaminocarbonyl) glycinamide, (monoaralkylaminocarbonyl) (alkyl) glycinamide, (monoarylaminocarbonyl) glycinamide, (monoarylaminocarbonyl) (alkyl) glycinamide, alaninamide, heterocyclyl and heterocyclylalkyl. A preferred group of compounds in this group of. subclass of compounds is the group. wherein: Rl is one or more substituents selected from the group consisting of. alkyl, cycloalkyl, hydroxyalkyl, hydroxyalkenyl, cyanoalkyl, alkoxyalkyl, monoalkylaminoalkyl, azidoalkyl, monoalkylureidoalkyl, aryloxyalkylcarbonyloxyalkyl, and heterocyclylalkyl; R 2 is one or more substituents selected from the group consisting of hydrogen, chloro or fluoro; R 3 is phenyl substituted by one or more substituents selected from the group consisting of hydroxy, halo, alkyl, alkoxy, formyl, nitro, cyano, aminoalkoxy, cycloalkylaminoalkyl, hydroxyalkyl, - (monoalkylamino) aralkyl, alkoxyalkyl, amino, monoalkylamino, dialkylamino, monoaralquilamino, alkylcarbonylamino, alkenylcarbonylamino, cicloalquilcarboniland.no, arylcarbonylamino, eterociclilcarbonilamino, haloalquilcar- bonilamino, alcoxialquilcarboniland.no, alcoxicarbonilal- 'quilcarboniland.no, alkylsulfonylamino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, monoaralquilaminoalquilo, alkylcarbonylaminoalkyl, carbonylaminoalkyl aryl-, ( alkylcarbonyl) (alkyl) aminoalkyl, (cicloalquialquil) aminoalkyl, alcoxicarbonilalquilcarbonilaminoalquilo, laminoalquilo alquilsulfoni-, (alkylsulfonyl) (alkyl) ami? Oalkyl, arylsulphonylaminoalkyl, (arylsulfonyl) (alkyl) aminoalkyl carboxy, alkoxycarbonyl, alquilcarbo- nile, (hydroxyalkoxy) Carbon ilo, aminocarbonyl, monoalkylaminocarbonyl, monoarylaminocarbonyl, (aminocarbonylalkyl) aminocarbonyl, (aminoalkyl) aminocarbonyl, (hydroxyalkyl) aminocarbonyl, hydroxyamidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, (monoalkyl) (monoaryl) ureido, (haloalkylcarbonyl) ureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl) (alkyl) ureidoalkyl, (alkoxycarbonylalkyl) ureidoalkyl, glycinamide, monoalkyl glycinamide,; aminocarbonylglycinamide, (alkoxyalkylcarbonyl) glycine, (aminocarbonyl) (al-quyl) glycinamide, (alkoxycarbonylalkylcarbonyl) (alkyl) glycinamide, (alkoxycarbonyl-5-laminoalkylcarbonyl) glycine-mido, arylcarbonylglycine-, (arylcarbonyl) (alkyl) ) glycinamide, (monoaralkylaminocarbonyl) (alkyl) glycinamide, (monoarylaminocarbonyl) glycinamide, (monoarylaminocarbohyl) (alkyl) glycinamide, alinamamido, heterocyclyl and heterocyc-0-chloroalkyl. A more preferred group in this subclass group of compounds are the compounds wherein: Rla is one or more substituents selected from the group consisting of alkyl and hydroxyalkyl; R2 is one or more substituents selected from the group consisting of hydrogen, chloro or fluoro; R3 is phenyl substituted by one or more substituents selected from the group consisting of halo, alkyl, alkoxy, -formyl, nitro, cycloalkylaminoalkyl, hydroxyalkyl, amino, alkylcarbonylamino, haloalkylcarbonylazole,. alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, alkylsulfonylamino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, (alkylsulfonyl) (alkyl) aminoalkyl, alkylcarbonyl, incarbonyloyl, monoalkylaminocarbonyl, monoarylaminocarbonyl, (aminocarbonylalkyl) aminocarbonyl, (aminoalkyl) aminocarbonyl, hydroxyamidino, ureido, ( haloalquilcarbo- * nil) ureido, ureidoalkyl, glycinamido, monoalquilglici- N-amido, aminocarbonilglicinamido, (alcoxialquilcarbo- nil) glycinamido, (aminocarbonyl) (alkyl) glycinamido, (alcoxicarbonilaminoalquilcarbonil) glycinamido, alaninamido, and heterocyclylalkyl. An even more preferred group of compounds in this subclass group of compounds are the compounds wherein R 2 is 4-fluoro and R 3 is phenyl substituted at the 4-position with chlorine and optionally substituted at the 2-position by aminocarbonyl, ureido, or glycinamide. The preferred compounds in this group are selected from the group consisting of the following compounds: (rans) -1- ((4-chlorophenylamino) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine 1- ((4-chloro-2- (aminocarbonyl) 'phenylamino) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; and 1- ((4-chlorophenylamino) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; Of the preceding subgroup of compounds, another preferred class of compounds are the compounds wherein: R4 is -C (R8) 2-; R 5 is methylene; R6 is -C (O) -; and each R8 is selected from the group consisting of hydrogen, alkyl, amino, monoalkylamino, dialkylamino, bonilamino alquilcar-, cycloalkylcarbonylamino, cycloalkylalkyl- carbonylamino, alkoxycarbonylamino, alkylsulfonylamino, arylcarbonylamino, alcoxicarbonilalquilcarbonilanu.no, alkylcarbonylaminoalkyl, chyle cicloalquilcarbonilaminoal-, alkoxycarbonylaminoalkyl, heterociclilcarboni- laminoalkyl, arylsulfonylamino, alkylsulfonylaminoalkyl, ureido, monoalkylureido, monohaloalkylureido, ureidoalkyl, monoalkyl ureidoalkyl, monohaloalkylidenealkyl, aminoalkyl, monoalkylaminoalkyl, and dialkylaminoalkyl. A preferred subclass of compounds of this class of compounds are the compounds wherein: Rla is one or more. substituents selected from the group consisting of halo, alkyl, cycloalkyl, cycloalkylaminoalkyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy) aralkyl ,. cyanoalkyl, haloalquilcarbonilaminoalquilo, alkoxyalkyl, aralkyl coxialquilo, alkylthioalkyl, hydroxyalkylthioalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, monoarilaminoalquilo, monoaralquilaminoalquilo, azidoalkyl, mohoalquilureidoalquilo, (lalquil alcoxicarboni-) ureidoalkyl, hydroxyalkylaminoalkyl, loxialquilcarboniloxialquilo ari-, loxialquilo aralcoxialquilcarboni-, alkylcarbonylalkyl, alcoxicarbpnilo, alkoxycarbonylalkyl , and heterocyclylalkyl; R 2 is one or more substituents selected from the group consisting of hydrogen and halo; R3 is phenyl which is optionally substituted by one or more substituents selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, aminoalkoxy, cycloalkyl, cycloalkylaminoalkyl, aralkyl, hydroxyalkyl , (monoalkylamino) aralkyl, alkoxyalkyl, amino, monoalkylamino, dialkylamino, monoaralqui- lamino, alkylcarbonylamino, alquenilcarboniland.no, ci- cloalquilcarbonilamino, arylcarbonylamino, alkoxycarbonylamino heterocyclyl-, haloalquilcarboniland.no, bonilamino alcoxialquilcar-, alcoxicarbonilalquilcarboniland.no, (alkylcarbonyl) ( alkyl) amino, alkylsulfonylamino, aminoalkyl, monoalquilaminaalquilo, dialkylaminoalkyl, monoarilaminoalquilo, monoaralquilaminoalquilo, nilaminoalquilo alquilcarbo-, arylcarbonylaminoalkyl, (alkylcarbonyl) (alkyl) aminoalkyl, (quil cicloalquial-) aminoalkyl, alkoxycarbonylaminoalkyl, alcoxicarbonilalquilcarbonilaminoalquilo, '(alkoxycarbonyl) (alkyl) to minoalkyl, alkylsulfonylaminoalkyl, (alkylsulfonyl) (alkyl) aminoalkyl, arylsulfoniland.no-alkyl, (arylsulfonyl) (alkyl) aminoalkyl, heterocyclylaminoalkyl, carboxy, alkoxycarbonyl, alkylcarbonyl, (hydroxyalkoxy) carbonyl, aminocarbonyl, monoalkylaminocarbonyl, monocarbaminocarbonyl, (aminocarbonylalkyl) aminocarbonyl, (aminoalkyl) aminocarbonyl, (hydroxyalkyl) aminocarbonyl, dialkylethanocarbonylalkyl, hydroxyamidino, ureido, monoalkylureido, monoaralkylidene, monoaralkylureido, • (monoalkyl) (monoaryl) ureido, (haloalkylcarbonyl) ureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl , monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl) (alkyl) ureidoalkyl, (alkoxycarbonylalkyl) ureidoalkyl, glycinamide, monoalkylglycinamido, aminocarbonylglycinamido, (alkoxyalkylcarbonyl) glycinamide, (amynocarbonyl) (alkyl) glycinamide, (alkoxycarbonylalkylcarbonyl) (alkyl) ) glycinamide, (al coxycarbonylaminoal-guilcarbonyl) glycinamide, arylcarbonylglycinamide, (arylcarbonyl) (alkyl) glycinamide, (monoaralkylarylcarbonyl) glycinamide, (monoaralkylaminocarbonyl) (alkyl) glycinamide, (monoarylaminocarbonyl) glycinamide, (monoarylaminocarbonyl) (alkyl) glycinamide, alaninamide, heterocyclyl and heterocyclylalkyl. A preferred group of compounds within this preferred subclass group of compounds are compounds wherein: Rla is one or more substituents selected from the group consisting of alkyl, cycloalkyl, hydroxyalkyl, hydroxyalkenyl, cyanoalkyl, alkoxyalkyl, monoalkylaminoalkyl, azidoalkyl, monoalquilureidoalquilo, ariloxialquilcarboniloxialquilo, and heterocyclylalkyl; R 2 is one or more substituents selected from the group consisting of hydrogen, chlorine or fluoro; R 3 is phenyl substituted by one or more substituents selected from the group consisting of hydroxy, halo, alkyl, alkoxy, formyl, nitro, cyano, aminoalkoxy, laminoalquilo ciclqalqui-, hydroxyalkyl, (monoalkylamino) aralkyl, alkoxyalkyl, amino, monoalkylamino, dialkylamino , monoaralkylamino, alkylcarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylaccarbonylamino, heterocyclylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, alkylsulfonylamino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, monoaralkylaminoalkyl, alkylcarbonylaminoalkyl, arylcarbonylaminoalkyl, alkylcarbonyl) (alkyl) aminoalkyl, (cicloalquialquil) aminoalkyl, alcoxicarbonilalquilcarbonilaminoalquilo, laminoalquilo alquilsulfoni-, (alkylsulfonyl) (alkyl) aminoalkyl, arylsulphonylaminoalkyl, (arylsulfonyl) (alkyl) aminoalkyl, carboxy, alkoxycarbonyl, alkylcarbonyl, (hydroxyalkoxy) carbo nyl, aminocarbonyl, monoalkylaminocarbonyl, monoarylaminocarbonyl, (aminocarbonylalkyl) aminocarbonyl, (aminoalkyl) aminocarbonyl, (hydroxyalkyl) aminocarbonyl, hydroxyamidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, (monoalkyl) (monoaryl) ureido, (haloalkylcarbonyl) ureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl) (alkyl) ureidoalkyl, (alkoxycarbonylalkyl) ureidoalkyl, glycinamide, monoalkylglycinamido, aminocarbonylglycinamido, (alkoxyalkylcarbonyl) glycine, (aminocarbonyl) (alkyl) glycinamide, (alcoxicarbo- nilalquilcarbonil) (alkyl) glycinamido, (laminoalquilcarbonil alcoxicarboni-) glycinamido, arilcarbonilglicina- measure, (arylcarbonyl) (alkyl) glycinamido, (minocarbonil monoaralquila-) (alkyl) glycinamido, (monoarilaminocarbonil) glycinamido, (monoarilaminocarbonil) ( alkyl) glycinamide, alaninamide, heterocyclic lyl and heterocyclylalkyl. A more preferred group of compounds within this subclass of compounds are the compounds wherein: Rla is one or more 'substituents selected from the group consisting of alkyl and hydroxyalkyl; R2 is one or more substituents selected from the group formed by hydrogen, chloro or fluoro; R3 is phenyl substituted by one or more substituents selected from the group consisting of halo, alkyl, alkoxy, - formyl, nitro, cycloalkylaminoalkyl, hydroxyalkyl, amino, alkylcarbonylamino, haloalkylcarbonylamino, coxialquilcarboniland.no al, mino alcoxicarbonilalquilcarbonila-, alkylsulfonylamino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, (alkylsulfonyl) (alkyl) aminoalkyl, alkylcarbonyl, aminocarbonyl, monoalkylaminocarbonyl, monoarylaminocarbonyl, (aminocarbonylalkyl) aminocarbonyl, (aminoalkyl) aminocarbonyl, hydroxyamidino, ureido, (haloalkylcarbonyl) ureido, ureidoalkyl, glycinamide, monoalkylglycinamide to inocarbonilglicinamido, (quilcarbonil alkoxyalkyl) glycinamido, (aminocarbonyl) (alkyl) glycinamido, '(Bonil alcoxicarbonilaminoalquilcar-) glycinamido, alaninamido, and heterocyclylalkyl. A still more preferred group of compounds of this subclass group of compounds are the compounds wherein: R 2 is 4-fluoro; R3 is phenyl substituted at the 4-position with chlorine and optionally substituted at the 2-position by aminocarbonyl, ureido, or glycinamide; and R8 is hydrogen and the other R8 is selected from the group consisting of amino, alkylcarbonylamino, lamino cicloalquilcarboni-, cicloalquilalquilcarboniland.no, alkoxycarbonylamino, alkylsulfonylamino, arylcarbonylamino, bonilalquilcarbonilamino alkoxycarbonyl, alkylcarbonylaminoalkyl, cicloalquilcarbonilaminoalquilo, 'alcoxicarbonilaminoal- quilo-, heterocyclylcarbonylaminoalkyl, arilsulfonila - mino, alkylsulfonylaminoalkyl, ureido, monoalquilu- laugh, monohaloalquilureido, ureidoalkyl, monoalquilureidoalquilo, monohaloalquilureidoalquilo, and aminoalkyl. Preferred compounds of this still more preferred group are the compounds selected from the group consisting of the following compounds: (trans) -1- (2- (4-chlorophenyl) -3- (methylsulfonylamino) propyl) carbonyl-2, 5- dimethyl-4- (4-fluorobenzyl) piperazineLko ; (trans) -1- (2- (4-chlorophenyl) -3- (acetylamino) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -2- (methylsulfonylamino) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -2- (acetylamino) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -2- (amino) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -2- (ureido) ethyl) carbonyl-2,5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -3- (ureido) propyl) carbonyl-2,5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -3- (amino) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -3- (-butoxycarbonylamino) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -2- ((ethoxycarbonylmethylcarbonyl-amino) ethyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -2- (N'-iso-propylureido) ethyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- ( 4-chlorophenyl) -2- (N '- (2-chloroethyl) ureido) ethyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2 - (4-chlorophenyl) -2- ((2-nitrophenyl) ca'rbonilami- no) ethyl) carbonyl-2, 5-dimethyl-4- (-4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -2- ((4-metoxifenilme- til) carbonylamino) ethyl) carbonyl-2, 5-dimethyl-4- (4- fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl ) -2- ((2,4-dinitrophenyl) sulfonyl-amino) ethyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) - 2- (cyclopropylcarbonylamino) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -2- ((2-cyclopropyl) - useful) carbonylamino) ethyl ) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -3- • ((2-methylpropyl) carbonylamino) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -3- (cyclopentylcarbonylamino) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -3- (N '- (t-butyl) ureido) propyl) carbonyl-2,5-dimethyl- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -3- (N'- (ethyl) ureido) propyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (Rans) -1- (2- (4-chlorophenyl) -3- (N '~ (3-choropropil) urei- do) propyl) carbonyl-2, 5-dimethyl-4- (4- fluorobenzyl) piperazine; and (trans) -1- (2- (4-chlorophenyl) -3- ((morpholin-4-yl) .carbonylamino) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine. Of the compounds of formula (la), another preferred group of compounds are compounds wherein: R3 is a heterocyclic ring system substituted by one or more substituents selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkylsulfonyl, ariisulfonilo , ay, hydroxyay, haloalkyl, formyl, nitro, cyano, haloay, alkenyl, alkynyl, aryl or aralkyl, amino, monoalkylamino, dialkylamino, onoarilamino, monoaralquilamino, alkylcarbonylamino, aycarbonylamino, alkenylcarbonylamino, cycloalkyl- carbonylamino, arylcarbonylamino, not haloalquilcarbonilami- , ayalkylcarbonylamino, bonilamino alcoxicarbonilalquilcar-, (alkylcarbonyl) amino (alkyl) (aycarbonyl) (alkyl) amino, alkylsulfonylamino, -aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, bonilaminoalquilo alquilcar-, arylcarbonylaminoalkyl, (alkylcarbonyl) (alkyl) aminoalkyl, aycarbonylaminoalkyl, carboxy, aycarbonyl, araycarbonyl, alky ilcarbonyl, arylcarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, monoarylaminocarbonyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylaminocarbonylalkyl, guanidino, ureido, monoalkylureido, ureidoalkyl, monoalkylureidoaikyl, and glycinamide. Of this group of compounds, a preferred subgroup of compounds is the group of compounds wherein: R4 is' -0-, - N (R7) - or -C (R8) -; R5 is an alkylene chain; R 7 is selected from the group consisting of hydrogen, alkenyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl; and each R8 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, hydroxy, alkoxy, hydroxyalkyl, alkoxyalkyl, amino, monoalkylamino, dialkylamino, alkylcarbonylamino, alkoxycarbonylamino cycloalkyl-, cicloalquilalquilcarboniland.no, alkoxycarbonylamino, alkylsulfonylamino, arylcarbonylamino , alcoxicarbonilalquilcarbonilamino, (alkylcarbonyl) (alkyl) amino, aralquilcarboniland.no, (aralkylcarbonyl) (alkyl) amino, alkylcarbonylaminoalkyl, cicloalquilcarbonilaminoalquilo, alcoxicarbonilaminoalqui- it, (alkylcarbonyl) (alkyl) aminoalkyl, nilaminoalquilo aralquilcarbo-, heterocyclylcarbonylaminoalkyl, (aralkylcarbonyl) (alkyl) aminoalkyl, arilsulfonilami- not, alkylsulfonylaminoalkyl, ureido, monoalquilureido, monohaloalquilureido, dialkylureido, ureidoalkyl, monoalquilureidoalquilo, dialquilureidoalquilo, monoha- loalquilureidoalquilo, aminoalkyl, monoalquilaminoal- chyle, dialkylaminoalkyl, carboxyalkyl, to coxycarbonylalkyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, and dialkylaminocarbonylalkyl. Of this subset of compounds, a preferred class of compounds are the compounds wherein: R 4 is -O-; R5 is methylene; and R 6 is -C (O) -. Of this class of compounds, a preferred subclass of compounds are compounds wherein: Rla is one or more substituents selected from the group consisting of halo, alkyl, cycloalkyl, cycloalkylaminoalkyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy) aralkyl, cyanoalkyl, haloalquilcar-bonilaminoalquilo, alkoxyalkyl, aralkyl coxialquiló, alkylthioalkyl, hydroxyalkylthioalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, monoarilaminoalquilo, monoaralquilaminoalquilo, azidoalkyl, monoalquilureidoalquilo, (lalquil alcoxicarboni-) ureidoalkyl, hydroxyalkylaminoalkyl, loxialquilcarboniloxialquilo ari-, loxialquilo aralcoxialquilcarboni-, alkylcarbonylalkyl , alkoxycarbonyl, -alkoxycarbonylalkyl, and heterocyclylalkyl; and R 2 is one or more substituents selected from the group consisting of hydrogen and halo. A preferred group of compounds in this preferred group of the subclass of compounds are compounds wherein R 3 is selected from the group consisting of azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuran-nile, benzothienyl, I carbazolyl , cinnofinyl, decahydroisoquinolyl, dioxolanyl, furyl, isothiazolyl, quinuclidinyl, imidazolyl, imidazolidyl, imidazolidinyl, isothiazolidinyl, indolyl, isoindolyl, indolinyl, isoindolinyl, indanyl, indolizinyl, isoxazolyl, isoxazolidinyl, morpholinyl, naphthyridinyl, oxadiazolyl, octahydroindolyl, octahydroisoindolyl , 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxoazepinyl, oxazolyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazole ynyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, tiaz'olilo, thiazolidinyl, thiadiazolyl, triazolyl, tetrazolyl, tetrahydrofuryl, tetrahydropyranyl, .tienilo, thiamorpholinyl, thiamorpholinyl sulfoxy-do, and thiamorpholinyl. A more preferred group of compounds in this preferred subclass group of compounds are compounds wherein R3 is benzopyranyl, benzopyranonyl, benzfuranilo, benzofuran-nile guiholinilo, indolyl, indolinyl, oxazolyl, imide-zolilo, or benzothienyl. A preferred compound in this most preferred group is (trans) -1- ((.benzo [b] pyran-2-on-7-yloxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine .

Another aspect of the invention is a method of treating endometrosis in a female human, and said method comprises administering to a female human in need of such treatment a therapeutic effective amount of a compound of formula (Ia) as has described. Preparation of compounds of the invention The following reaction schemes are for the preparation of compounds of formula (Ia). It is understood that those compounds of the invention that are not specifically prepared in the following reaction schemes can be prepared by similar synthesis processes by appropriately substituting the raw materials and reagents. It is also understood that in the following descriptions, combinations of the different substituents (for example, substituents Rla, R2 and R3) in the formulas shown are allowed only if said combinations give stable compounds. For convenience purposes only, the preparation of compounds of the invention where R3 is only phenyl is illustrated below. It is understood that other groups R3. (Which include other carbocyclic and heterocyclic ring systems) can be prepared in a similar manner.

It is also understood that during the preparation of the compounds of the invention, as described below, additional reactive groups (eg, hydroxy, amino or carboxy groups) on intermediary compounds that are used in the preparation can be protect as necessary by the appropriate protecting group by treating the intermediate compound prior to the desired reaction with the appropriate protecting group precursor using methods known to those of ordinary skill in the art. The protecting groups can then be removed as desired using methods known to those of ordinary skill in the art, e.g., by acid or basic hydrolysis. Said protecting groups and methods are described in detail in Greene, T.W. and Wuts, P.G. M., "Protective Groups in Organic Synthesis", 2nd Edition, 1991, John Wiley & Sons. In addition, dimethylpiperazines can be prepared in an asymmetric synthesis according to the method summarized in Mickelson, J.W. , Belonga, K.L., Jacobsen, E.J., Journal of Organic Chemistry (1995), Vol.60, pp.4177-4123. It should be noted that the only difference between the two groups of compounds encompassed by formula (la) and formula (Ib) as described below is that the substitution of the piperazine ring in the compounds of formula (Ia) is regulated. . Therefore, it is understood that, unless stated otherwise, the following reaction schemes have as an object the preparation of compounds of formula (Ib) which can be used to prepare the compounds of formula (la). A. Preparation of Compounds of Formula (C) The compounds of formula (C) are intermediates in the preparation of the compounds of the invention. They are prepared according to the following reaction scheme 1 where R lal is one or more substituents Rla which is independently selected as described above in the summary of the invention for the compounds of formula (la) (except that Rlal can be not being aminoalkyl or monoalkylaminoalkyl unless protected appropriately); X is chlorine, bromine or iodine, and R 2 is as described above for the compounds of formula (Ia): Reaction Scheme 1 . (A) (B) (C) The compounds of formula (A) and formula (B) can be obtained commercially, eg, from Aldrich Chemical Co. or Sigma Chemical Co., or can be prepared in accordance with methods known to those with a normal experience in art. In general, the compounds of formula (C) are prepared by treating a compound of formula (A) in an organic solvent, such as for example methylene chloride, with an equimolar amount of a compound of formula (B). The reaction mixture is stirred for between about 10 and 20 hours at room temperature. Then the re-action mixture is concentrated to yield a residue that is dissolved in an organic solvent. The compound of formula (C) is isolated from the solution by standard isolation techniques, eg, by filtration, concentration and rapid column chromatography. B. Preparation of Compounds of Formula (Ga) and Formula (Gb) The compounds of formula (Ga) and formula (Gb) are intermediates in the preparation of compounds of the invention. They are prepared as illustrated in the following reaction scheme 2 wherein each Rlal is independently selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, cycloalkylaminoalkyl, (cycloalkylalkyl) aminoalkyl, haloalkyl, alkenyl, alkynyl, aralkyl, aralkenyl. , formyl-1-alkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy) aralkyl, (hydroxy) cycloalkylalkyl, mercaptoalkyl, cyanoalkyl, haloalkylcarbonylaminoalkyl, (alkoxy) aralkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkylthioalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, monoarylaminoalkyl, monoaralkylaminoalkyl, alkylcarbonylaminoalkyl, (alkylcarbonyl) (alkyl) aminoalkyl, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, alkoxycarbonylaminoalkyl, hydroxyalkylaminoalkyl,. aryl-xialquilcarboniloxialquilo, alcoxialquilcarboniloxialquilo, aralcoxialquilcarboniloxialquilo, alkylcarbonylalkyl, carboxyalkyl, alkoxycarbonylalkyl, aralcoxicarbonilal-chyle, aminocarbonyl, monoalquilaminocarbonilalqui-lo, dialkylaminocarbonylalkyl, monoarilaminocarbonilal-chyle, monoaralquilaminocarbonilalquilo, heterocyclyl and heterocyclylalkyl (except that Rlal can not be aminoal-chyle or monoalkylaminoalkyl not ' be protected appropriately): Reaction Scheme 2 (D) - (E) (F) (F) The compounds of formula (D) and formula (E) can be obtained commercially, for example, from Aldrich Chemical Co. or Sigma Chemical Co., or can be made using methods known to those of ordinary skill in the art. art . In general, compounds of formula (Ga) and formula (Gb) are prepared by treating, first a compound of formula (D) in an anhydrous aprotic solvent, such as anhydrous ether, with an equimolar amount of a compound of formula (E) in an anhydrous aprotic solvent, such as anhydrous ether, for a period of time, for example, for a period of two hours. The resulting reaction mixture is stirred for between about 2 and about 4 hours, preferably about 3 hours, at room temperature. The compound of formula (F) is isolated from the reaction mixture by standard isolation techniques, such as, for example, product concentration and purification by vacuum distillation. To a solution of a strong reducing agent, such as for example lithium aluminum hydride, in an anhydrous polar aprotic solvent, such as for example tetrahydrofuran, is added the compound of formula (F). The resulting mixture is stirred at room temperature for between about 30 minutes and about 2 hours, preferably about 1 hour. The mixture is then heated to reflux to complete the reaction. Upon completion, the compound-formula (Ga) is isolated from the reaction mixture by standard isolation techniques, such as by cooling with water and a soft base, followed by filtration. As an alternative, to a solution of formula. (F) in a protic solvent. polar, such as for example absolute ethanol, is added to solid alkali metal, such as, for example, sodium metallics over a period of time, such as for a period of 3 hours. The resulting mixture is heated to reflux for between about 2 and about 4 hours, preferably about 3 hours. The compound of formula (Gb) is distilled from the reaction mixture by adding water to the reaction mixture. The distillate is then treated with an aqueous acid, such as, for example, hydrochloric acid, to form the salt of the compound of formula (Gb). Then, the compounds of formula (Ga) and formula (Gb) can be treated with compounds of formula (B) in a manner similar to that described above in reaction scheme 1 to produce compounds of the invention where orientation is fixed relative of Rla substituents. C. Preparation of Compounds of Formula (Ia) The compounds of formula (Ia) are compounds of the invention and are prepared as illustrated in the following reaction scheme 3 wherein each X is independently chloro or bromo; Rlal is one or more substituents Rla being independently selected as described above in the Summary of the Invention for compounds of formula (Ia) (except gue R lal can not contain a primary or secondary amine unless be protected so appropriate); R2, R4 and R5 are as described in the summary of the invention for the compounds of formula (la) (except that R4 and R5 may not contain a primary or secondary amine unless protected appropriately); and R3a is one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alguilo, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alquilsulfonilalqui-- it, alkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy) cycloalkylalkyl, cycloalkylamino, cycloalkylaminoalkyl, (quil cicloalquilal-) amino, (cicloalquialquil) aminoalkyl, cyanoalkyl, alkenyl, alkynyl, 'aryl, aralkyl, aralkenyl, hydroxyalkyl, - (hydroxy) aralkyl, hydroxyalkylthioalkyl, Hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy) aralkyl, aryloxyalkyl, aralkoxyalkyl, amino, monoalkylamino, dialkylamino, monoarylamino, monoaralquila- mino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, hydroxyalkylaminoalkyl, monoarilaminoalquilo, monoaralquilaminoalquilo, alkylcarbonylamino, (Bonil alquilcar-) (alkyl) amino, alkylcarbonylaminoalkyl, (alkyl- carbonyl) (alkyl) aminoalkyl, alkoxycarbonylamino, (alkoxycarbonyl) (alkyl) amino, alkoxycarbonylaminoalkyl, (alkoxycarbonyl) (alkyl) aminoalkyl carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, alquilcarbonilal-chyle, arylcarbonyl, arylcarbonylalkyl, aralkylcarbonyl , aralquilcarbonilalquilo, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alcoxialquilcarboni-loxialquilo, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, monoarilaminocarbonilo, monoaral-quilaminocarbonilo, aminocarbonyl, mono-alkylcarbonyl, dialkylaminocarbonylalkyl, monoarilami-nocarbonilalquilo, monoaralquilaminocarbonilalquilo, amidino, guanidino, ureido, monoalquilureido, dialkylureido, ureidoalkyl, monoalquilureidoalquilo, dialquilureidoal-chyle, heterocyclyl and heterocyclylalkyl; and R4 and R5 are as described above in the summary of the invention: Reaction Scheme 3 (H) (J) (K) (B) (a) The compounds of formula (B), formula (H) and formula (J) can be obtained commercially, for example, from Aldrich Chemical Co. or Sigma Chemical Co., or they can be prepared at -5. according to methods known to those with a normal experience in art. In general, the compounds of formula (la) are prepared by the above reaction scheme by first treating a compound of formula (H) in a polar solvent, co-0 mo for example methanol, with an equimolar amount of a compound of formula (J) in an anhydrous polar solvent, such as; for example anhydrous ether. The resulting reaction mixture is stirred at room temperature for between about 5 minutes and about 24 hours in the presence of a base to neutralize the acid, for example triethylamine, then the compound of formula (K) is isolated. ) of the reaction mixture by standard isolation techniques, such as extraction of the organic phase, evaporation of solvents and purification by flash column chromatography The compound of formula (K) is treated in a polar aprotic solvent, eg tetrahydrofuran, with an excess molar amount of a compound of formula (B) in the presence of a soft base, such as, for example, triethylamine and, optionally, a catalytic amount of sodium iodide. it is stirred at room temperature for between about 1 and 5 days, preferably for about 2 days, then the compound of formula (Ia) is isolated from the reaction mixture by means of ai techniques. standard solution such as filtration, concentration of volatiles and purification by rapid column chromatography. Alternatively, in this reaction scheme, instead of the compounds of formula (H), the compounds of formula (-Ga) and formula (Gb) can be used, as prepared earlier in reaction scheme 2, to produce compounds of the invention where the relative orientation of the substituents Rla is fixed. D. Preparation of Compounds of Formula (Ia) The compounds of formula (Ia) are compounds of the invention and are prepared as illustrated in the following reaction scheme wherein X is chloro, bromo or an activated ester; P1 and P2 are independently nitrogen protecting groups, such as for example t-butoxycarbonyl (P1 can also be hydrogen); Rla, R2, R4 and R5 are according to each other. described earlier in the summary of the invention; Rlb is as described above in the summary of the invention for the compounds of formula (le) and (Id); and R3a is one or more substituents that are independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, aryloxy, haloalkyl,. formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy) cycloalkylalkyl, cycloalkylamino, cycloalkylaminoalkyl, (cycloalkylalkyl) amino, (cycloalkylalkyl) aminoalkyl, cyanoalkyl, alkenyl, al-quinyl, aryl. , aralkyl, aralkenyl, hydroxyalkyl, (hydroxy) aralkyl, hydroxyalkylthioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy) aralkyl, aryloxyalkyl, aralkoxyalkyl, amino, monoalkylamino, dialkylamino, monoarylamino, monoaralquilamino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, hydroxyalkylaminoalkyl, monoarilaminoalquilo, monoaralquilaminoalq uilo, alkylcarbonylamino-, (alkylcarbo- 'nyl) (alkyl) amino, alkylcarbonylaminoalkyl, (alkylcarbonyl) (alkyl) aminoalkyl, - alkoxycarbonylamino, (alkoxycarbonyl) (alkyl) amino, alkoxycarbonylaminoalkyl, (alkoxycarbonyl) (alkyl) aminoalkyl, carboxy, alkoxycarbonyl, aralc.oxycarbonyl, alkylcarbonyl, alkylcarbonylalkyl-, arylcarbonyl, arylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, Carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, loxialquilo alcoxialquilcarboni-, 'aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, monoarilaminocarbonilo, monoaral- 15 quilaminocarbonilo, aminocarbonyl, alkylcarbonyl monoalquiland.no-, dialquilaminocarbonilalquilo-, monoarilami- nocarbonilalquilo, monoaralquilaminocarbonilalquilo, amidino, guanidino, ureido, monoalquilureido, dialkylureide, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, heterocyclyl and heterocyclylalkyl: Reaction scheme 4 (D (M) (N) (O) Reaction Scheme 4 (continued) (la) The compounds of formula (L), formula (N), formula (P) and formula. (J) can be obtained commercially, for example, from Aldrich Chemical Co. or Sigma Chemical Co., or -5 can prepare according to methods known to someone with a normal experience in the art. The compounds of formula (L) wherein the Rlb substituent contains a deprotected hydroxy group can be protected with the appropriate oxygen protecting group before the synthesis of the compound of formula (M). The removal of the protecting group can be carried out as desired. In general, the compounds of formula (la) are first prepared by esterifying a compound of formula (L) by treating the compound with a molar amount in. excess of a lower alkanol, preferably methanol, in the presence of an acid, preferably hydrochloric gas, at between about 0 ° C and room temperature. The resulting mixture is then stirred at between about 0 ° C and the reflux temperature, preferably at room temperature, for between about 4 hours and about 18 hours. The mixture is then concentrated by removal of solvents to produce the compound of formula (M). To a solution of the compound of formula (M) in an organic solvent, as per. For example, methanol, at about 0 ° C and room temperature, is added an excess molar amount of a compound of formula (N), and then treated with a mild acid, such as acetic acid, "and stir at room temperature for between about 2 hours and about 4 hours, preferably about 3 hours, to form an imine intermediate.The imine is then reduced in situ by treatment with a reducing agent, such as sodium cyanoborohydride, to produce a compound of formula (O), which is isolated from the reaction mixture by standard isolation techniques, such as filtration and purification by rapid column chromatography, to a solution of a compound of formula (P) in a polar aprotic solvent, such as, for example, anhydrous tetrahydrofuran, a mild base is added to neutralize the acid, such as N-methylmorpholine, followed by the addition of a reagent coupling acid, such as for example isobutyl chloroformate. The resulting mixture is stirred at about 0 ° C to room temperature for between about 15 minutes and about 2 hours, preferably about 15 minutes at 0 ° C and then for about an hour at room temperature, to form an intermediate active ester of the compound of formula (P). The intermediary is then treated in situ with a compound of formula (O) in anhydrous polar aprotic solvent, such as anhydrous tetrahydrofuran, and the resulting mixture is stirred at room temperature for between about 10 hours and about 24 hours, preferably for about 15 hours. The compound of formula (Q) is isolated from the reaction mixture by standard isolation techniques, such as concentration, separation of the organic phase and purification by flash column chromatography. The compound of the formula (Q) is then treated in an aprotic solvent, such as, for example, methylene chloride, at about 0 ° C, with a strong organic acid, such as, for example, trifluoroacetic acid. For a period of between about 2 and about 4 hours, preferably about 2 hours, to remove the protecting group on the nitrogen atom, followed by spontaneous cyclization to form the compound of formula (R), which is isolates from the reaction mixture by standard isolation techniques, such as, for example, neutralization with a soft base. See, filtration and concentration. The compound of formula (R) in an anhydrous aprotic or polar solvent, such as, for example, anhydrous tetrahydrofuran, at about 0 ° C is treated with a strong reducing agent., such as, for example, lithium aluminum hydride. The resulting mixture is then heated to reflux for between about 12 hours and about 24 hours, preferably about 15 hours. The mixture is then cooled to room temperature and the reaction mixture is cooled with water, followed by an aqueous base, preferably aqueous potassium hydroxide. The resulting mixture is allowed to stir at room temperature for between about 30 minutes and one hour. The compound of formula (S) is then isolated from the reaction mixture by filtration and concentration. The compound of formula (S) is added in a polar aprotic solvent, such as, for example, methylene chloride, in the presence of an excess amount of a base to neutralize the acid, such as, for example, triethylamine, a slightly molar amount. in excess of a compound of formula (J) in a polar aprotic solvent, such as, for example, methylene chloride. The resulting mixture is stirred at room temperature for between about 15 minutes and about 1 hour, preferably about 15 minutes. The compound of formula (Ia) is then isolated from the reaction mixture by standard isolation techniques, such as extraction, concentration and rapid column chromatography. E. Preparation of Compounds of Formula (Ib) Compounds of formula (Ib) are prepared as illustrated below in reaction scheme 5 where X is chlorine or bromine; Rlb is as described above in the summary of the invention for Rla- of the compounds of, formula (la) and hydrogen; and R2 is as described above in the summary of the invention for the compounds of formula (la); R3a is one or more substituents that are independently selected from the group consisting of hydrogen, halo, alkyl, alkoxy, aryloxy, haloalkyl, formyl, nitro, cyano, aralkoxy, haloalkoxy, cycloalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, amino, monoalkylamino, dialkylamino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, cycloalkylaminoalkyl, carboxy, coxicarbonilo al, aryloxycarbonyl, aralkoxycarbonyl, carboxyalkyl, alkoxycarbonylalkyl, aryloxycarbonylalkyl, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, aminocarbonylalkyl, monoalquilaminocarbonilalqui- it, dialkylaminocarbonylalkyl, arylsulfonyl, hydroxyalkoxy, aminoalkoxy, (monoalkylamino) aralkyl, aminoalkylamino, heterocyclylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocycliccarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonyl ao, alkoxycarbonylalkylcarbonylamino, alkylsulfonylamino, arylcarbonylaminoalkyl, -alkoxycarbonylalkylcarbonylaminoalkyl, alkylsulfonylaminoalkyl, (alkylsulfonyl) (alkyl) aminoalkyl, arylsulphonylaminoalkyl,. (arylsulfonyl) (alkyl) aminoalkyl, heterocyclylaminoalkyl, (hydroxyalkoxy) carbonyl, (aminocarbonyl) aminocarbonyl, (monoalkylaminocarbonylalkyl) aminocarbonyl, (carboxyalkyl) aminocarbonyl, (al-coxycarbonylalkyl) aminocarbonyl, (aoalkyl) aminocarbonyl, (hydroxyalkyl) aminocarbonyl, dialkylaminocarbonyloxyalkyl, monoarylureido, monoaralkylureido, monoalkalkylureido, (monoalkyl) (monoaryl) ureido, diarylureido, (haloalkylcarbonyl) ureido, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl) (alkyl) ureidoalkyl, (alkoxycarbonylalkyl) ureidoalkyl, glycinamide, monoalkylglycinamido, (alkoxyalkylcarbonyl) glycinamide, aminocarbonylglycinamide, (aminocarbonyl) (alkyl) glycinamide, (alkoxycarbonylalkylcarbonyl) (alkyl) glycinamide, (alkoxycarbonylaminoalkylcarbonyl) glycinamide, arylcarbonylglycinamido, (arylcarbonyl) (alkyl) giicinamido, (monoaralkylaminocarbonyl) glycinamide, (monoaralk ilaminocarbonyl) (alkyl) glycinamide, (monoarylaminocarbonyl) glycinamide, (monoarylaminocarbonyl) (alkyl) glycinamide, glycinamidoalkyl, alaninamide, monoalkylalaninamide, alaninamidoalkyl, heterocyclyl and • heterocyclylalkyl; and Ra is -O- or -N (R7a) - where R 7a is hydrogen, alkyl, aryl. or aralkyl: Reaction scheme 5 (T) (Ib) Compounds of formula (U) are commercially available, for example from Aldrich Chemical Co. or Sigma Chemical Co .., or may be prepared according to methods known gue aguellos ordinary skill in art. Compounds of formula (T) can be prepared according to the methods described herein for the compounds of formula (C) or for the compounds of formula (K), or by adding compounds of formula (C) as prepared here using standard methods known to those with normal experience in the art. In general, compounds of formula (Ib) are prepared by the above reaction scheme by first treating a compound of formula (T) in an anhydrous aprotic solvent such as anhydrous dimethylformamide exemplar, with a molar amount slightly in 'excess of a formu- late compound (U) in the presence of a soft base, such as, for example, potassium carbonate. The resulting mixture is stirred at about 50 ° C for between about 10 hours and about 24 hours, preferably for about 15 hours. The compound of formula (Ib) is then isolated from the reaction mixture by standard isolation techniques, such as extraction, filtration and precipitation. F. Preparation of Compounds of Formula (Ib) Compounds of formula (Ib) can also be prepared as illustrated in the following reaction scheme wherein X is chloro, bromo or an activated ester; P1 is a nitrogen protecting group, such as for example t-butoxycarbonyl; Rlb is as described above in the summary of the invention for the compounds of formula (le) and formula (Id); R2a is as described above in the summary of the invention for R2 in compounds of formula (le) except that R2a may not be formyl or formylalkyl; R3a is one or more substituted-tes independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alquilsufonilp, alkylthioalkyl, alquilsulfinilal-chyle, alkylsulfonylalkyl, alkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy) cycloalkylalkyl, cycloalkylamino, laminoalquilo cicloalqui-, (cycloalkylalkyl) amino, (cicloalquial- quil) aminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl , aralkyl, aralkenyl, hydroxyalkyl, (hydroxy) aralkyl, hydroxyalkylthioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy) aralkyl, aryloxyalkyl, aralkoxyalkyl, amino, monoalkylamino, dialkylamino, monoarylamino, monoaralquilamino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, hydroxyalkylaminoalkyl, monoarilaminoalquilo, monoaralquilaminoalqu yl, alkylcarbonylamino, (alkylcarbonyl) (alkyl) amino, alkylcarbonylaminoalkyl, (alkylcarbonyl) (alkyl) aminoalkyl, alkoxycarbonylamino, (alkoxycarbonyl) (alkyl) amino, alkoxycarbonylaminoalkyl, (alkoxycarbonyl) (alkyl) aminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, alkylcarbonylalkyl, arylcarbonyl, arylcarbonylalkyl, aralquilcarboni-lo aralquilcarbonilalquilo, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alcoxialquilcarboni-loxialquilo, ami-nocarbonilo, monoalkylaminocarbonyl, dialkylaminocarbonyl, monoarilaminocarbonilo, monoaral- quilaminocarbonilo, aminocarbonyl, alkylcarbonyl monoalquilamino-, dialkylaminocarbonylalkyl, monoarilami- nocarbonilalquilo, monoaralquilaminocarbonilalquilo, amidino, guanidino, ureido, monoalquilureido, dialkylureido, ureidoalkyl, monoalquilureidoalquilo, chyle diálquilureidoal-, heterocyclyl and heterocyclylalkyl; and Ra is. -0- or -N (R7a) - wherein R7a is hydrogen, alkyl, aryl or aralkyl: Reaction Scheme 6 (V) (U) (W) (K) The compounds of formula (U) and formula (N) can be obtained commercially, for example, from Aldrich Chemical -Cp. or Sigma Chemical Co., or can be prepared according to methods known to those of ordinary skill in the art. The compounds of formula (V) can be prepared according to the method described above for the compounds of formula (K) in the reaction scheme 3. In general, the compounds of formula (Ib) as prepared in the above reaction scheme 6 are prepared by first treating a compound of formula "(U) in an aprotic solvent such as dimethylformamide for example, at about 0 ° C, with a strong base, such as potassium hexamethylene tildisílazida , to deprotonate the compound The resulting mixture is stirred for between about 20 minutes and one hour, preferably for between about 20 minutes and about 0 ° C. An equimolar amount of a compound of formula (V) is then added to the mixture. an aprotic solvent, such as, for example, dimethylformamide and the resulting mixture is stirred at room temperature for between about 1 and 24 hours, preferably for about 2 hours.Then the compound is isolated of formula (W) from the reaction mixture by standard isolation techniques, such as extraction and concentration. The protective group P1 of the compound of formula (W) is then removed to form a compound of formula (K) by means of standard methods of deprotection of amines, for example by treating the compound of formula (W) with a strong acid, for example , trifluoroacetic acid. To a solution of the compound of formula (K) in a polar solvent, such as, for example, methanol, at about 0 ° C to room temperature, an excess molar amount of a compound of formula ( N), and then treated with a mild acid such as, for example, acetic acid, and stirred at room temperature for between about 2 hours and about 4 hours, preferably for about 3 hours, to form an imine intermediate. . The imine is then reduced in if your by treatment with a reducing agent, eg sodium cyanoborohydride, to produce a compound of formula (Ib) which is isolated from the reaction mixture by standard isolation techniques, such as p .ej filtration and purification by flash column chromatography. G. Preparation of compounds of formula (Ib) The compounds of formula (Ib) can also be prepared as illustrated in the following reaction scheme 7 where R 1 is as described above in the summary of the invention for the compounds of formula ( le) and formula (Id); and R2 is as described above e. the summary of the invention for the compounds of formula (Ib); and R3a is one or more substituents independently selected from the group consisting of hydrogen ,, hydroxy, sulfonyl hydroxy, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, ara? coxi, haloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy) cycloalkylalkyl, cycloalkylamino, ci- cloalquilaminoalquilo, (cycloalkylalkyl) amino, (cycloalkylene quialquil) aminoalkyl, cyanoalkyl, alkenyl, alkynyl , aryl, aralkyl, aralkenyl, "hydroxyalkyl, (hydroxy) aralkyl, hydroxyalkylthioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy) aralkyl, aryloxyalkyl, aralkoxyalkyl, amino, monoalkylamino, dialkylamino, monoarylamino, monoaralquilamino, aminoalkyl, monoalkylaminoalkyl • dialkylaminoalkyl , hydroxyalkylaminoalkyl, monoarylaminoalkyl, monoaralk ilaminoalquilo, alkylcarbonylamino, (alkylcarbonyl) (alkyl) amino, alkylcarbonylaminoalkyl, (alkylcarbonyl) (alkyl) aminoalkyl, alkoxycarbonylamino, (alkoxycarbonyl) (alkyl) amino, alkoxycarbonylaminoalkyl, (alkoxycarbonyl) (alkyl) aminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, Alkylcarbonylalkyl, arylcarbonyl, arylcarbonylalkyl, aralkylcarbonyl, aralquilcarbonilalquilo, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, chyle alcoxialquilcarboniloxial-, aminocarbonyl, monoalkylaminocarbonyl, inocarbonilo dialkylamide, monoarilaminocarbonilo, monoaralquilamino- carbonyl, aminocarbonyl, monoalquilaminocarbonilal- chyle, dialkylaminocarbonylalkyl, monoarilaminocarboni- lalquilo, monoaralquilaminocarbonilalquilo, amidino , guanidium, ureido, monoalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, heterocyclyl and heterocyclylalkyl: Reaction scheme (X) (Y) (C) (Ib) The compounds of formula (X) can be obtained commercially, for example, from Aldrich Chemical Co. or Sigma Chemical Co-. , or can be prepared according to methods known to those with ordinary experience in the art.

The compounds of formula (C) can be prepared according to the methods described herein. In general, the compounds of formula (Ib) prepared according to this reaction scheme are prepared by first treating a compound of formula (X) in an organic solvent, such as, for example, toluene, with phosgene for a period of time. between about 1 hour and about 24 hours, preferably about 2 hours, at reflux temperature to form the isocyanate of formula (Y), which is isolated from the reaction mixture by standard isolation techniques, such as concentration and filtration. The compound of the formula (Y) is then treated in a polar solvent, anhydrous aprotic, such as for example tetrahydrofuran, with an equimolar amount of a compound of the formula (C). The resulting mixture is stirred at room temperature for between about 10 hours and about 48 hours, preferably about 20 hours, then the compound of formula (Ib) is isolated from the reaction mixture by standard isolation techniques, such as example concentration and evaporation of solvents In addition to the above reaction templates 1 to 7, other compounds of the invention can be made using reactions known to one skilled in the art, for example, a compound of formula (la), or any raw material or intermediary thereof substituted in an appropriate manner, where at least one Rla substituent or The least one Rlb substituent is selected from the group consisting of hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy) aralkyl, (hydroxy) cycloalkylalkyl, hydroxyalkylthioalkyl, and hydroxyalkylaminoalkyl, it may be dissolved in a polar aprotic solvent, as per - example methylene chloride, in the presence of a soft base to neutralize the acid and then it can be treated with a slightly excess molar amount of a sulfonyl halide, such as for example sulfonyl chloride, para. forming an intermediate compound containing a leaving group 15. sulfonate. The compound can then be dissolved in an anhydrous aprotic solvent, such as, for example, dimethylformamide, and treated, in the presence of a soft base, with the appropriate nucleophilic reagent to form compounds of formula (la), or with any suitable raw material or intermediate. Or the same substituted in an appropriate manner, where the Rla substituent or the Rlb substituent (depending on the nucleophilic reagent being used) can be selected from the group consisting of heterocyclylalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, cycloalkylamino, cyanoalkyl, (cycloalkylalkyl) aminoalkyl, or hydroxyalkylthioalkyl. Alternatively, a form compound may be treated, or any raw material or intermediate thereof suitably substituted with a hydroxy group, such as, for example, hydroxyalkyl, hydroxyalkenium, hydroxyalkynyl, (hydroxy) aralkyl, ( hydroxy) cycloalkylalkyl, hydroxyalkylthioalkyl, and hydroxyalkylaminoalkyl, with a mild oxidizing agent, such as, for example, oxalyl chloride, which is dissolved in an inert organic solvent, such as, for example, methylene chloride, to which DMSO is added during a period of time at between about -60 ° C and about 0 ° C, preferably at about -50 ° C. The reaction mixture is stirred at about -60 ° C to about 0 ° C for between about 15 minutes and about one-hour, preferably about 15 minutes, and then a mild base, such as e.g. eg trietila-mina. The mixture is allowed to gradually warm to room temperature, at which point the oxidized compound (ie, the corresponding aldehyde) of formula (la), or any appropriately substituted raw material or intermediary thereof, is isolated from the reaction mixture by standard isolation techniques. Alternatively, a compound of formula (Ia), or any appropriately substituted raw material or intermediary thereof, which contains an aldehyde or a ketone group, such as, for example, formyl, alkylcarbonyl or alkylcarbonylalkyl, can be treated with the suitable organometallic reagent, such as, for example, an organomagnesium or organolithium, under standard Grignard synthesis reaction conditions to form the corresponding hydroxy-substituted compounds. Alternatively, a compound of formula (Ia), or any raw material or intermediary thereof appropriately substituted containing a hydroxy group, such as for example hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, -. (hydroxy) aralkyl, - (hydroxy) cycloalkylalkyl, hydroxyalkylthioalkyl, and hydroxyalkylaminoalkyl, in an anhydrous polar solvent, such as, for example, anhydrous ether, in the presence of a strong base, such as, for example, sodium hydride, can be treated with a halide of alkyl, such as for example methyl iodide, at room temperature, to form the corresponding alkoxy-substituted compounds. Alternatively, a compound of formula (la), or any raw material or intermediary thereof substituted in an appropriate manner, can be reacted where at least one substituent Rla or at least one substituent R 1b is formyl or formylalkyl, with a primary or secondary amine, under conditions of reductive amination as described above for the preparation of the compounds of formula (0) or the compounds of formula (Ib) as prepared in reaction scheme 6 to form the corresponding compounds of formula (Ia), or any raw material or intermediary thereof appropriately substituted, where "the R a substituent or the R 1 substituent is monoalkylaminoalkyl, dialkylaminoalkyl, monoaralkylaminoalkyl, or hydroxyalkylaminoalkyl." Alternatively, a compound of formula (la), or any raw material or intermediary thereof substituted in an appropriate manner that contains a group "ester, such as for example an alkoxycarbonyl, aryloxycarbonyl or aralkoxycarbonyl group, under standard conditions of basic hydrolysis, to form the corresponding compound of formula (Ia), or any raw material or intermediary thereof substituted in an appropriate manner containing a acid group, ie a carboxy group Alternatively, a compound of formula (la), or any raw material or intermediary thereof appropriately substituted, where R6 is -C (0) - can be reduced to give the corresponding compound of formula (la), or any material, cousin or intermediary thereof substituted in an appropriate manner, where R6 is -CH2- using methods known to those of ordinary skill in the art, eg, by the method it was described above for the compounds of formula (S) In addition, the compounds of formula (Ia), or any raw material or intermediary thereof substituted in an appropriate manner, wherein R6 is -C (O) - is can convert into a compound of formula (la), or any raw material or intermediary thereof appropriately substituted, where Rs is -C (S) - by treatment with Lawesson's reagent under standard conditions known to those with normal experience in the art. In addition, the compounds of formula. (la), or any raw material or intermediary thereof substituted in an appropriate manner, • containing an atom of. Non-oxygenated sulfur can be oxidized with the appropriate sulfur oxidizing agent according to methods known to those skilled in the art, such as using hydrogen peroxide, to produce the corresponding compounds containing a sulfinyl or sulfonyl group instead thereof. Alternatively, compounds of formula (Ia), or any raw material or intermediary thereof substituted in an appropriate manner containing a carboxy group can be converted to compounds containing the corresponding amide group by first converting the carboxy group into an activated ester or anhydride is mixed using, for example, isobutyl chloroformate in the presence of a mild base, such as, for example, N-methylmorpholine, in an aprotic solvent, such as THF, and then treating the ester with The primary or secondary amine is suitably substituted in an aprotic solvent, such as THF, alternatively, the compounds of the formula (-la), or any raw material or intermediary thereof substituted in an appropriate manner containing a The cyano group can be converted into compounds containing a hydroxyamidino group by reaction with hydroxyamine in a polar solvent, such as DMSO. prepare in situ by first treating the hydrochloride salt of the hydroxyamine with a base, such as, for example, triethylamine. Alternatively, the compounds of formula (Ia), or. any raw material or intermediary thereof substituted in an appropriate manner containing a hydroxy group, can be converted into the compounds containing the corresponding azide group by treating the compound with trifexylphosphine and an alkyl azodicarboxylate, for example azodicarboxylate diethyl, in an aprotic solvent, such as for example THF, and then displacing the activated oxygen that was formed in that manner with a source azide, such as for example d-ifenylphosphorylazide, in an aprotic solvent, such as, for example, THF. Alternatively, the compounds of formula (Ia), or. any raw material or intermediary thereof appropriately substituted, containing a group -NH2 or a group -Ra-NH can be converted into compounds having -5 have a corresponding group -Ra-N (H) -C (O ) - reacting the compound with a substituted acid halide in an appropriate manner under standard acylation conditions. Alternatively, the compounds of formula (Ia), or any raw material or intermediary thereof substituted appropriately, which contain an acid halide group (-C (O) -X -where X is halo) or an activated ester group can be "converted into compounds containing the corresponding group -C (0) -N (H) - making reacting the compound with a primary or secondary amine appropriately substituted under standard conditions of acylation or amide linkage formation As an alternative, the compounds of formula (Ia), or - any raw material or intermediary thereof substituted in a manner The amine group can be converted into compounds containing the corresponding aminoalkyl group in a manner similar to the conversion of formula (M) to formula (0) in the reaction scheme 4. In particular, the amine it reacts with an appropriately substituted aldehyde to form the intermediary -imine, which is then reduced by treatment with an appropriate reducing agent, such as, for example, sodium cyanoborohydride. Alternatively, the compounds of formula (Ia), or any raw material or intermediary thereof suitably substituted, containing a primary or secondary amine can be converted into the compounds containing the corresponding ureido group by reacting the compound with phosgene in a manner similar to the above 7 'reaction scheme (in an aprotic solvent) to form the corresponding isocyanate, which is then reacted with the primary or secondary amine appropriately substituted. In addition, all the compounds of the invention that exist in free base or free acid form can be converted into their salts. acceptable for pharmaceutical use - by treatment with the appropriate organic or inorganic acid, or by the appropriate organic or inorganic base. The salts of the compounds of the invention can also be converted to the free base form or the free acid form or to another salt using methods known to those skilled in the art. The following specific preparations and examples are given as a guide to assist in the practice of the invention, and are not given as limiting the scope of the invention. In the following preparation and examples, all NMR data refer to 1 H NMR spectrum data and are given in the format of "(multiplicity, number of hydrogens)". The yield of each of the reactions described here is expressed as a percentage of the theoretical yield. PREPARATION 1 Compounds of Formula (C) A. To a solution of 2-methylpiperazine (0.10 g, 1 mmol) in CH 2 Cl 2 (2 mL) was added 4-fluorobenzyl bromide (0.125 mL, 1 putiol). The resulting mixture was stirred at room temperature. After 15 hours, the mixture was concentrated in vacuo to give a solid. This solid was dissolved in CH2C12 and washed consecutively with water, aqueous NaHCO3 solution, then brine. The organic layer was dried over. MgSO, filtered, and concentrated to form u? oil. Purification by flash column chromatography gave 0.025 g (12% yield) "of 1- (4-fluorobenzyl) -3-methylpiperazine, a compound of formula (C), as a colorless oil.; NMR (CDC13) 7.3 (m, 2), 7.0 (m, 2), 3.4 (s, 2), 3.0-2.6 (m, 5), 2.0 (br s) , 2), 1.6 (t, 1), 1.0 (d, 3) ppm. B. In a similar manner, the following compounds of formula (C) were prepared: (2R, 55) -1- (chloro) acetyl-4- (4-fluorobenzyl) -2,5-dimethylpiperazine-1- (4-fluorobenzyl) piperazine; (trans) -1- (4-fluorobenzyl) -2,5-dimethylpiperazine; (cis) -1- (4-fluorobenzyl) -2,3-dimethylpiperazine; (trans) -1- (4-fluorobenzyl) -2,, 3-dimethylpiperazine; and (cis) -1- (4-fluorobenzyl) -3,5-dimethylpiperazine. C. similarly, other compounds of formula (C) are prepared.

PREPARATION 2 Compounds of Formula (F) A. To a solution of ethylenediamine (13 g, 216 mmol) in anhydrous ether (600 mL) was added 2,3-butanedione (18.6 g, 216 mmol, in 200 mL anhydrous ether). ) by dripping over 2 hours, the resulting mixture was stirred at room temperature. After 3 hours, the clear solution was concentrated in vacuo to give a brown oil, purification by vacuum distillation gave 16.6 g (70% yield) of 5,6-dimethyl-2,3-dihydropyrazine, a compound of formula (F), as a limpid yellow oil; b.p. 60 ° C / 16 mm Hg, NMR (CDC13) 3.3 (br s, 4), 2.1 (s, 6) ppm. B. similarly, other compounds of formula (F) are prepared. PREPARATION 3 Compounds of formula (Ga) A. To a solution of lithium aluminum hydride (0.36 g, 10 mmol) in anhydrous tetrahydrofuran (50 mL) was carefully added 5,6-dimethyl-2,3-dihydropyrazine ( 1.0 g, 9 mmol, in 10 mL of anhydrous tetrahydrofuran). The resulting mixture was stirred at room temperature for 1 hour, then heated to reflux. After completion of the reaction, as determined by thin layer chromatography of the reaction mixture, the reaction mixture was cooled to room temperature and set by consecutive addition of 0.4 mL of water, 0.4 mL of aqueous solution of 15% NaOH, then 1.2 mL of water. After brief agitation, the mixture was filtered through a fritted funnel. The filtrate was concentrated to yield 0.92 g (90% yield) of (cis) -2,3-dimethylpiperazine, a compound of formula (Ga), as a clear yellow oil; .RMN (CDC13) 2.7 (m, 4) -, 2, -5 (m, 2), 0.9 (d, 6) ppm. B. in a similar manner, other compounds of formula (Ga) are obtained. PREPARATION 4 Compounds of formula (Gb ') A.- To a solution of 5,6-dimethyl-2,3-dihydropyrazine (2.3 g, 21 mmol) in absolute ethanol (60 mL) was added sodium metal (6). , 5 g, 280 mmol) in reduced portions over a period of 3 hours. The resulting mixture was heated to reflux. After 3 hours at reflux, the product was distilled from the mixture while gradually adding 200 mL of water to the reaction vessel. The distillate was treated with 1N aqueous HCl solution and concentrated in vacuo to give. a semi-solid Titration with acetone gave 0.78 g (20% yield) of (trans) -2,3-dimethylpiperazine, a compound of formula (Gb), as an orange solid; NMR (DMSO-de) 9.8 (br s, 4), 3.5-3.2 (m, 6), 1.2 (s, 6) ppm .. B. similarly, other compounds are prepared of formula. (Gb) PREPARATION 5 Compounds of Formula (K) A. To a solution of (cis) -2,6-dimethylpiperazine (0, -115 g, 1.1 mmol) in methanol (35 mL) was added 4-chlorophenoxyacetyl chloride, ( 0.205 g, 1.0 mmol, in 6 mL solution of anhydrous ether). The resulting mixture was stirred at room temperature - for 10 minutes and then triethylamine (0.10 mL, 0.72 mmol) was added. After 30 minutes, the mixture was concentrated in vacuo to give an oily residue. This was taken up in ether and washed with saturated aqueous NaHCO 3 solution, then brine. The organic layer was separated, dried over MgSO4, filtered and concentrated in vacuo to give an oil. Purification by flash column chromatography gave 0.202 g (80% yield) of (cis) -l - ((4-chlorophenoxy) methyl) carbonyl-3,5-dimethylpiperazine, a compound of formula (K), a limpid oil and in- color NMR (CDC13) 7.3 (d, 2), 6.9 (d, 2), 4.7 (d, 1), 4.6 (d, 1), 4.4 (d, 1), 3 , 8 (d, 1), 2.7 (m, 3), 2.2 (t, 1), 1.1 (m, 6) ppm. B. In a similar manner, the following compounds of formula (I) were prepared: (35, 55) -1- ((4-chlorophenoxy) methyl) carbonyl-3,5-dimethylpiperazine; and (3R, 5R) -1- ((4-chlorophenoxy) methyl) carbonyl-3,5-dimethylpiperazine. C. in a similar manner, prepare other compounds of formula (K), PREPARATION 6 Compounds of Formula (M) • A. A solution of (2R) -3-benzyloxy-2- (N - (t-butoxycarbonyl) acid ) amino) propanoic (23 g, 78 mmol, [OI] D -4.4 ° (c = 2, H20)). in methanol (250 mL) was cooled to 0dC and HCl (g) was bubbled into the solution until saturation. The resulting mixture was stirred at room temperature for 17 hours and then concentrated in vacuo to give 17 g (100% yield) of (2R) -3-benzyloxy-2-aminopropanoic acid methyl ester, a compound of formula (M ), as a white solid; NMR (DMSO-d 6) 8.7 (br s, 3), - 7.4-7.3 (m, 5), 4.5 (q, 2), 4.4 (br s, 1), 3.8 (s, 2), 3.7 (s, 3) ppm. B. similarly, other compounds of formula (M) are prepared. PREPARATION 7 Compounds of Formula (0) A. A solution of (2R) -3-benzyloxy-2-aminopropanoic acid methyl ester (19 g, 78 mmol) in methanol (350 mL) under N2 was cooled to 0 ° C. and acetic acid (2 g, pH 2) was added, followed by the addition of 4-fluorobenzaldehyde, a compound of formula (N) (12.5 mL, 117 mmol) and sodium cyanoborohydride (7.3 g, 117 mmol. ) and molecular sieves 3 Á (15 g). The resulting mixture was stirred at "room temperature" for 3 hours, then filtered through Celite (MeOH) - The filtrate was concentrated in vacuo to give a clear liquid.This was taken up in ethyl acetate and washed consecutively with aqueous 10% Na 2 CO 3 solution, water, then brine, the organic phase was then dried over MgSO 4, filtered, and concentrated in vacuo, purification by column chromatography on silica gel gave -14, 7 g (60% yield) of (2R) -3-benzyloxy-2- (N- (4-fluorobenzyl) amino) propanoic acid methyl ester, a compound of formula (0), as a clear and colorless oil; (CDCl 3) 7.4-7.2 (m, 7), 7.0 (dd, 2), 4.5 (d, 2), 3.9- 3.5 (m, 8) ppm, MS ( LSIMS) 317. B. In a similar manner, the following compounds of formula (O) were prepared: (2R) -2- (N- (4-fluorobenzyl) amino) propanoic acid methyl ester (2S) -methyl ester - 2- (N- (4-fluorobenzyl) amine) propanoic; or (2R) -2- (N- (-fluorobenzyl) amino) -methylthiobutanoic; (2R) -2- (N- (4-fluorobenzyl) amino) -3-methoxypropanoic acid methyl ester; acid methyl ester (2 R) -2- (N- (4-fluorobenzyl) amino) - 3- ((2-hydroxyethyl) thio) propanoic acid; and (2R) -2- (N- (4-fluorobenzyl) amino) -3-methylbutanoic acid methyl ester. C. similarly, the following compounds of formula (O) are prepared: (25) -2- (N- (4-fluorobenzyl) amino) -4-methylthiobutanoic acid methyl ester; (25) -2- (N- (4-fluorobenzyl) amino) -3-methoxypropanoic acid methyl ester; methyl ester of (25) -2 (N- (4-fluorobenzyl) amino) -3- ((2-hydroxyethyl) thio) propanoic acid; (25) -2- (N- (4-fluorobenzyl) amino) -3-methylbutanoic acid methyl ester; (2 R) -2- (N- (4-fluorobenzyl) amino) butanoic acid ethyl ester; Ethyl ester of (25) -2- (N- (4-fluorobenzyl) amino) butanoic acid; (2R) -2- (N- (4-chlorobenzyl) amino) butanoic acid methyl ester; (2S) -2- (N- (4-chlorobenzyl) amino) butanoic acid methyl ester; (2R) -2- (N- (4-chlorobenzyl) amino) -4-methylthiobutanoic acid methyl ester; methyl ester of (2 R) -2- (N- (4-chlorobenzyl) amino) -3-methoxypropanoic acid; (2R) -2- (N- (4-chlorobenzyl) amino) -3- ((2-hydroxyethyl) thio) propanoic acid methyl ester; and (2R) -2- (N- (4-chlorobenzyl) amino) -3-methylbutanoic acid methyl ester. D .. similarly, other compounds of formula (O) are prepared.

PREPARATION 8 Compounds of Formula (Q) A. To a solution of Nt-butoxycarbonyl-D-alanine (5.6 g, 30 mmol, [a] or + 23 ° (c = 2, CH3C02H)) in anhydrous tetrahydrofuran (150 L) under? 2 at 0 ° C was added N-methylmorpholine (3.0 g, 30 mmol), followed by the addition of isobutylchloroformate (3.7 mL, 30 mmol), resulting in the formation of a white solid. The resulting suspension was stirred at 0 ° C for 15 minutes, and then at room temperature for 1 hour. A solution of (2R) -3-benzyloxy-2- (N- (4-fluorobenzyl) -amino) propanoic acid methylester (7.5 g, 24 mmol, in 50 mL of anhydrous tetrahydrofuran) was added to the mixture and the resulting mixture was stirred at room temperature. After 15 hours, the mixture was filtered through Celite (tetrahydrofuran). The filtrate was concentrated in vacuo to give a yellow liquid, which was dissolved in ethyl acetate, washed with water and then with brine. The organic phase was separated * then dried over -MgSO4, filtered, and concentrated in vacuo. Purification by column chromatography on silica gel gave 7.3 g (63% yield) of (2R) -3-benzyloxy-2- (N- (4-fluorobenzyl) -N- ((( ) -1- (t-butoxycarbonylamino) ethyl) carbonyl) amino) propanoic, a compound of formula (Q), as a limpid oil; NMR (CDCl 3) 7.4-7.2 (m, 7), 7.0 (dd, 2), 5.3 (d, 2), 4, -9- 4.3 (m, 5), 4 , 1-3.7 (m, 4), 1.6 (s, 9), 1.0 (d, 3) ppm. similarly, the following compounds of formula (Q) were prepared: acid methyl ester (2.R) -2- (N- (4-fluorobenzyl) -N- (((15) -1- (t-butoxycarbonylamino) ethyl) carbonyl) amino) propanoic; (25) -2- (N- (4-fluorobenzyl) -N- (((15) -1- (t-butoxycarbonylamino) ethyl) carbonyl) amino) propanoic acid methyl ester; (2R) -2- (N- (4-fluorobenzyl) -N- (((IR) -1- (-butoxycarbonylamino) ethyl) carbonyl) amino) propanoic acid methyl ester; (25) -2- (N- (4-fluorobenzyl) -N- (((IR) -1- (t-butoxycarbonylamino) ethyl) carbonyl) amino) propanoic acid methyl ester; (2R) -2- (N- (4-fluorobenzyl) -N- (((15) -1- (t-butoxycarbonylamino) ethyl) carbonyl) amino) -4-methylthiobutanoic acid methyl ester; (2R) -2 ~ (N- (4-fluorobenzyl) -N- (((1S) -1- (t-butoxycarbonylamino) ethyl) carbonyl) amino) -3-methoxypropanoic acid methyl ester; (2R) -2- (N- (4-fluorobenzyl) -N- (((15) -1- (t-butoxycarbonylamino) ethyl) carbonyl) amino) -3- ((2-hydroxyethyl) ') methyl ester thio) propanoic; (2R) -2- (N- (4-fluorobenzyl) -N- (((15) -1- (t-butoxycarboniland.no) ethyl) carbonyl) amino) -3-methylbutanoic acid methyl ester; and (2R) -2- (N- (4-fluorobenzyl) -N- (((15) -1- (t-butoxycarbonylamino) -2- (ethoxycarbonyl) ethyl) carbonyl) amino) propanoic acid methyl ester.

C. similarly, other compounds of formula (Q) are prepared. PREPARATION 9 Compounds of Formula (R) A. To a solution of (2R) -3-benzyloxy- 2- (N- (4-fluorobenzyl) -N- (((15) -1- (-butoxycarbonylamino)) methyl ester. ethyl) carbonyl) amino) propanoic acid (2.0 g, 4 mmol) in CH2 Cl2 (25 mL) was cooled to 0 ° C and trifluoroacetic acid (25 mL) was added dropwise over 2 hours. At the end of the addition, the ice bath was removed and the mixture was stirred at room temperature.After 2 hours, the mixture was concentrated in vacuo.The residual yellow oil was captured in ethyl acetate and washed with a solution. NaHC03 1N aqueous layer. The organic layer was separated then dried over MgSO4, filtered, and concentrated in vacuo to give 1.2 g (83% yield) of (2R, 55) -1- (4-fluorobenzyl) ) -2- (benzyloxy) methyl-5-methyl-piperazine-3,6-dione, 'a compound of formula (R) -, as a limpid oil; NMR (CDC13) 7.4-7.2 (m, 7), 7.0 (dd, 2), 5.0 (d, 1), 4.5-4.0 (m, 4), 3.9-3.5 (m, 4) -, 1, 5 (d, 3) 'ppm, MS- (LSIMS) 356. B. In a similar manner, the following compounds of formula (R) were prepared: (2R, 55) -1- (4-fluorobenzyl) -2 , 5-dimethylpiperazine-3,6-dione; '(25,55) -1- (4-fluorobenzyl) -2,5-dimethylpiperazine-3,6-dione; (2R, 5R) -1- (4-fluorobenzyl) -2, 5-dimethylpiperazine-3,6-dione; (25.5.R) -1- (4-fluorobenzyl) -2,5-dimethylpiperazine-3,6-dione; (2 R, 55) -1- (4-Fluorobenzyl) -2- (2-methylthioethyl) -5-ethylpyrrazine-3,6-dione; (2R, 55) -1- (4-fluorobenzyl) -2- (methoxymethyl) -5-methylpiperazin-3,6-dione; (2R, 55) -1- (4-Fluorobenzyl) -2- ((2-hydroxyethyl) thiomethyl) -5-methylpiperazine-3,6-dione; (2R, 5S) -1- (4-fluorobenzyl) -2- (1-methylethyl) -5-methylpiperazin-3,6-dione; and (2R, 55) -1- (4-fluorobenzyl) -2-methyl-5- (ethoxycarbonyl) methylpiperazin-a-3,6-dione. C. - In a similar manner, other compounds of formula (R) are prepared: PREPARATION 10 Compounds of Formula (S) A. To a suspension of '(2R, 55) -1- (Arfluorobenzyl) -2- (hydroxy) methyl-5-methylpiperazin-3,6-dione (2.0 g, 7.5 mmol) in anhydrous tetrahydrofuran (50 mL) under N2 at 0 ° C was carefully added lithium aluminum hydride (2.2 g, 60 mm'ol). The resulting suspension was heated to reflux. After 15 hours, the mixture was cooled to room temperature and carefully set with water (2 mL), then aqueous INOH KOH solution (6 mL). The resulting suspension was stirred at room temperature for 30 minutes, then filtered through Celite _ (ethyl acetate). The filtrate was concentrated to the vacuum to give 1.6 g (90% yield) of (2R, 5S) -1- (4-fluorobenzyl) -2- (hydroxy) methyl-5-methylpiperazine, a compound of formula ( S), as a white solid; "NMR • (.CDC13) 7.3 (dd, 2), 7.0 (dd, 2), 4.2-4.0 (m, 2), 3.5 (d, 1) 3.0 ( m, 2), 2.7 (m, 2), 1.7 (m, 1), 1.0 (d, 3).

B. similarly, the following compounds of formula (S) were prepared: (2R, 55) -1- (4-fluorobenzyl) -2,5-dimethylpiperazine; (25, 55) -1- (4-fluorobenzyl) -2,5-dimethylpiperazine; (2R, 5R) -1- (4-fluorobenzyl) -2,5-dimethylpiperazine; (25, 5R) -1- (4-fluorobenzyl) - • 2,5-dimethylpiperazine; (2R, 55) -1- (4-fluorobenzyl) -2- (2-methylthioethyl) -5-methylpyrrazine; (2R, 55) -1- (4-fluorobenzyl) -2- (methoxymethyl) -5-methylpiperazine; '(2R, 55) -1- (4-fluorobenzyl) -2- ((2-hydroxyethyl) thiomethyl) -5-methylpiperazine; (2R, 55) -1- (4-fluorobenzyl) -2- (1-methylethyl) -5-methylpipe-razine; and (2R, 55) -1- (4-fluorobenzyl ') -2-methyl-5- (ethoxycarbonyl) methylpiperazine. • - - -C. in a similar manner, other compounds of formula (S) are prepared. PREPARATION 11 Compounds of formula (W) A. To a solution of 3, 4, 5-trimethoxyphenol (2.8 g, 15 mmol) in DMF (60 mL) at 0 ° C was added potassium hexamethyldisilazide (32 mL, i6). mmol, 0.5 M solution in toluene). The resulting mixture was stirred at 0 ° C. After 20 minutes, 1- (chloro) acetyl-4- (t-butoxycarbonyl) piperazine (4.6 g, 15 mmol, in 15 mL of DMF) was added and the mixture was stirred at room temperature. After 2 hours the mixture was poured into water and extracted with ethyl acetate. The organic layer was separated, dried over MgSO4, filtered and concentrated in vacuo to give 6.5 g (100% yield) of 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-4- ( -butoxycarbonyl) pi-0 perazine, a compound of formula (W), as a yellow solid; NMR (CDCl 3) 7.2 (m, 2), 4.6 (s, 2), 3.8 (m, 9), 3.6 (m, A), 3.4 (m, 4), 1.5 (s, 9) ppm.- B. In a similar manner, the following compounds of formula (W) are prepared: 5. 1- ((4-chlorophenyl) methyl) carbonyl-4- (t-butoxycarbonyl) piperazine; (3R) -1- ((4-chlorophenyl) methyl) carbonyl-3-methyl-4- (t-butoxycarbonyl) piperazine; (35) -1- ((4-chlorophenyl) methyl) carbonyl-3-methyl-4- (t-0-butoxycarbonyl) piperazine; and 1- ((4-chlorophenyl) methyl) carbonyl-3- (2- ((((4-chlorophenoxy) methyl) carbonyl) oxy) ethyl.) -4- (-butoxycarbonyl) piperazine.

C. in a similar manner, other compounds of formula (W) are prepared. PREPARATION 12 Compounds of formula (Y) 5. A. To a solution of 4-chlorobenzylamine (0.50 g, 3.5 mmol) - in toluene (15 mL) was added phosgene (7.3 mL, 14 mmol, 1 , 93 M solution in toluene). The resulting mixture was stirred at room temperature for 15 minutes, then heated to reflux. After 2 hours at reflux, the mixture was cooled to room temperature and concentrated in vacuo to give 0.70 g (100% yield) of 4-chlorobenzylisocyanate, a compound of formula (Y), as a yellow liquid; NMR (CDC13) 7.4-7.2 (m, 4), 4.4 (m, 2) ppm. - B. In a similar manner, other compounds of formula are prepared. (Y) . EXAMPLE 1 Compounds of Formula (Ia) and Formula (Ib) A. To a solution of (2R, 5S) -1- (4-fluorobenzyl) -2- (hydroxy) methyl-5-methylpiperazine (1.6 g, 6 , 7 mmol) in CHC12 (30 mL) was added triethylamine (excess) and 4-chlorophenoxyacetyl chloride (1.5 g, 7.4 mmol, per mL solution of CH2C12). The resulting mixture was stirred at room temperature. After 20 minutes, analysis by analytical TLC showed that the total consumption of starting material was. had produced. The mixture of volatiles was concentrated in vacuo and the residue was captured • 5 en.CH2Cl2. This was washed with saturated aqueous NaHCO 3 solution, then water, then brine, dried over MgSO 3, filtered, and concentrated in vacuo. Purification by column chromatography on silica gel yielded 2.16 g (79% yield) of (2R, 5R) -1- (- (4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((hydroxy) 'methyl) piperazine, as a yellow solid foam: NMR (DMSO-d 6) 7.7 (br s, 2), 7.3 (m, 4) , 6.9 (d, 2), 5.0-4.2 (m, 5), 4, 0-3, 2. (m, 7), 1. 2 (m, 3) ppm; MS (LSIMS) 406. 15 B. similarly, other compounds of formula (la) "were prepared: 1- ((4-chlorophenoxy) methyl) carbonyl-4- (4-fluorobenzyl) -5-methylpiperazine, trifluoroacetic acid; NMR (DMSO-dg) 7.6 (m, 2), 7.3 (m, 4), 6.9 (m, 2), 5.0-20.8 (m, 6), 3.5 -2.8 (m, 5), 1.4 (m, 3) ppm; 4- (4-fluorobehyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-ethylpiperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3-methylpiperazine; 4-benzyl-l- ((4-chlorophenoxy) methyl) carbonyl-2-phenylpiperazine; (2R) -4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (1-methylethyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (methoxymethyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-ethylpiperazin-3-one; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-ethylpiperazine; NMR (CDC1 3) 7.3 (m, A), 7.0 (t, 2), 6.9 (d, 2), 4.6 (s, 2), 4.4"(, 1), 3.7 (m, 1), 3.4 (,, 2), 2.8 (m, 2), 2.0-1.7 (m, 5), 0.9 (m, 3) ppm; (25) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (2-methylpropyl) piperazine; (trans) -A- (4-fluorobenzyl) -1- ( (4-chlorophenoxy) methyl) carbonyl-2", 5-dimethylpiperazine; NMR (CDC1 3) 7.3 (m, A), 7.0 (t, 2), 6.9 (d, 2), 4.6 (m, 2), 4.2 (m, 1), 3.6-3.0 (m, 5), 2.7 (dd, 1) -, 2.2 (d, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; (2R) -A- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-benzylpiperazine; - (benzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2'-phenylpiperazin-3-one; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (2-hydroxyethyl) piperazine; NMR (CDC13) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.7. (m, 3), 3.8-3. 2 5 (m, 5), 2.8 (m, 2), 2.2 (m, 2), 2.0 (ra, 2), 1.7 (m, 2) ppm; (cis) -A- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2,6-dimethylpiperazine; NMR (DMSO-d6) 7.6 (m, 2), 7.3 (m, 4), 6.9 (d, 2), 4.8 (m, 3), 4.4 (m, 3) , 0 3.3 (d, 2), 3.0 (m, 2), 1. 4 (m, 6) ppm; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (1-methylpropyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2'-methylpiperazine, hydrochloride salt; (2., 55) -4- (4-fluorobenzyl) -l- ((4-chlorophenoxy) methyl) carbonyl-2,5-dimethylpiperazine; 'NMR (CDC13) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), "4.6 (m, 2), 4.2 (m, 1) , 3.6-3.0 (m, 5), 2.7 (dd, 1), 2.2 (d, 1), 1.3 (m, 3), 0.9 (m, 3). ppm; (2R) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (2-methylpropyl) piperazine; 4- (4-fluorobenzyl) -1- ((4 chlorophenoxy) methyl) carbonyl-2- (butyl) piperazine; (2R, 5S) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (2-hydroxyethyl) -5-methylpiperazine; NMR (CDC13) 7.3 (m, A), 7.0 (t, 2), 6.9 (m, 2), 4.6 (m, 3), 3.5 (m, 5), 3 , 2 (dt, 1), '3.0 (m, 1), 2.8 (dd, 1), 2.2 (m, 2), 1.6 (m, 2), 1.0 (d) , 3) ppm; (2 5, 5R) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2,5-dimethylpiperazine; NMR (CDC13) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.6 (m, 2), 4.2 (m, 1), 3 , 6-3.0 (m, 5), 2.7 (dd, 1), 2.2 (d, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; (2S, 5S) -4- (4- fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2,5-dimethylpiperazine, "hydrochloride salt; NMR (DMSO-d6) 7.6 (m, 2) ), 7.2 (m, 4), 6.9 (d, 2), 4.8 (m, 2), 4.4 (m, 1), 4.1 (t, 1), 3, 9-2.9 (m, 6), 1.5-1.2 (m, 6) ppm; (2R, 5R) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl -2, 5-dimethylpiperazine hydrochloride salt; NMR (DMSO-de) 7.6 (m, 2), 7., 2 (m, A), 6.9 (d, 2), 4.8 (m, 2 ), 4.4 (m, 1), 4.1 (t, 1), 3, -9-2.9 (m, 6), 1.5-1.2 (m, 6) ppm; - ( 4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (1,1-dimethylethyl) piperazine; (25) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (2-methylpropyl) piperazine; (2 R, 55) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (2- ((4- chlorophenoxy) methyl) carbonyl) oxy) ethyl-5-methylpiperazine; NMR (CDC13) 7.2 (m, 6), 7.0 (m, 2), 6.8 (m, 4), 4.7-4 , 0 (m, .7), 3.6 (m, 2), 3.4 (m, 1), 3.1 (m, 1), 2.6 (m, 1), 2.3 (m, 2), 2.0 (m, 2) , 1. 0 (d, 3) ppm; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (methoxycarbonyl) methylpiperazine; (2S) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonanyl-2-propylpiperazine; (cis) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) -methyl) -carbonyl-2,3-dimethylpiperazine, hydrochloride salt; NMR '' (DMSO-d e) 7.6 (m, 2), 7.2 (m, A), 6.9 (m, 2), 5.0-4.1 (m, 6), 3 5-2.9 (m, 4), 1.5-1.2 (m, 6) ppm; (2R) -A- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-benzylpiperazine; (2 R) -A - (4-fl? Orobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-propylpiperazine; NMR (CDC13) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.6 (m, 2), 4.4 (m, 1), 3 , 7 (m, 1), 3.4 (m, 2), 3.0 (m, 1), 2. 'l (, 2), 2,0-1,6 (m, A), 1.2 (m, 2), 0.9 (m, 3) ppm; - (4- fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (ethoxycarbonyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxyethyl) piperazine; NMR (CDC13) 7. 3 (m, 4), 7.0 (t, 2), 6.9 (dd, 2), 4.7 (d, 2), 4.0-3.4 (m, , 8), 2.8 (m, 2), 2.3 (m, 1), 1.8 (m, 3) ppm; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (hydroxymethyl) piperazine; NMR (CDCl 3) 7.3 (m, 4), 7.0 (t, 2), 6.9 (t, 2), 4.7 (d, 2), 3.9-3. 2 (m, 7), 2.8-2.2 (m, 4) ppm; (25) -A- (4-fluorobenzyl) 1- ((4-chlorophenoxy) methyl) carbonyl-2-butylpiperazine; (2R, 6R) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2,6-dimethylpiperazine, hydrochloride salt; NMR (CDCl 3) 7. 7 (br s, 2), '7.2 (m, 4), 6.8 (d, 2), 4.6 (s,' 2), 4.4 (m, 3 ), 3.9 (m, 1), 3. 5 (m, -1-), - 3.2 (m, -l), 2.8 - (m-, 2), l, -6 - (.s, 6) ppm; (25, 6S) -4- (-fluorobenzyl) -1- ((-chlorophenoxy) methyl) carbonyl-2,6-dimethylpiperazine, hydrochloride salt; NMR (CDCl 3) 7. 7 (br s, 2), 7.2 (m, 4), 6.8 (d, 2), 4.6 (s, 2), 4.4 (m, 3), 3.9 (m, 1), 3. 5 (m, 1), 3.2 (m, 1), 2.8 (m, 2), 1.6 (s, 6) ppm; 4- (4-fluorobenzyl) -1- (((4-chlorophenoxy) methy1 carbonyl) spiro [cyclopropan-1,2 '-piperazine]; NMR (CDC13) 7.3 (m, A), 7.0-6.8 (m, 4), 4.6 (m, A), 2.8 (m, 2), 2.2-1, 6 (m, 4) ppm; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (trifluoromethyl) piperazine; 5 (2R, 55) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5- (2-methylthio) ethylpiperazine, hydrochloride salt; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (((((4-chlorophenoxy) methyl) carbonyl) oxy) methyl-10-piperazine; (25) - A - (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-propylpiperazine; NMR (CDC13) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.6 (s, 2), 3.8 (m, 2), 3 , 4 (m, 2), 3.2 (m, 2), 2.6 (m, 1), 2.4 (m, 1), 2.2 (m, 1), 5 1.6-1 . 3 (m, -A), 0.9 (m, 3) ppm; '- - (2R, 55) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) car-; Bonyl-2-methyl-5- (1-methylethyl) piperazine; NMR (DMSO-de) 7.6 (m, 2), 7.3 (m, A), 6.9 (d, 2), 5.0-4.2 (m, 6), 3. 5- 3.1 (m, A), 2.2 (m, 1), 1.2 (d, 3), 0.9 0 (d, 6) ppm; (2S) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (2-methylpropyl) piperazine; (2R, 3R) -A - (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2,3-dimethylpiperazine, hydrochloride salt; NMR (DMSO-de) 7.8 (m, 2), 7.3 (m, 4), 6.9 (d, 2) ', 5.1- 3.6 (m, 6), 3.2 (m, 4), 1.5-1.2 (m, 6) ppm; (35) -4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3-butylpiperazine; -. (35) -4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (1-methylpropyl) piperazine; (3R) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-methylpropyl) piperazine; (3R) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3-butylpiperazine; (2R, 5R) -A- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) car- 'bonyl-2-methyl-5- (benzyloxy) methylpiperazine; NMR (CDC13) 7.3 (m, 8), 6.8 (m,, 5), 4.5 (m, 6), 3.6 (m, 5), 3.0 (m, i.) , 2.7 (dd, 1), 2.3 (d, 1), 1.2 (d, 3) ppm; - (4- fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxyethyl) piperazine, dihydrochloride salt; (2R) -A- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methylpiperazine hydrochloride salt; (2R, 55) -A- (4-fluorobenzyl) -1- ((4-chlorophoroxi) methyl) carbonyl-2-methyl-5- ((4-acetylpiperazin-1-yl) methyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- ((trifluoroacetylamino) methyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (ethoxycarbonyl) methylpiperazine, hydrochloride salt; (2R, 5S) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2,5-dimethylpiperazine, hydrochloride salt; (trans) -A- (4-fluorobenzyl) -1- ((2-acetylamino-4-chlorophenoxy) methyl) carbonyl-2,5-dimethylpiperazine; NMR (DMSO-de) 9.5 (br s, 1), 8.1 (br s, 1), 7.7 (m, 2), 7.3 (m, 2), 7.0 (m, 2), 5.0 (m, 2), 4.3 (m, 3), 3.8-2.9 (m, 5), 2.1 (s, 3), 1.2 (m, 6) ppm; 4- (4-fluorobenzyl) -1- ((2- ((acetylamino) methyl) -4-chlorophenoxy) methyl) carbonyl-2,5-methylpiperazine; NMR (CDC13) '7.3 (m, 3), 7.1 (dd, 1), 7.0. (t, 2), 6.7 (d, 1), 4.7 (m, 2), 4.2-3.4 (m, 10), 3.0 (br s, 1), - 2.7 (dd, 1), 2.5 (q, A), 2.2 (d, 1), 2.0 (m, 4), 1.3 (m, 3), 0.9 ( m, 3) ppm; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (((t-butoxycarbonyl) amino) methylpiperazine; 1- ((4-chloro-2- (acetylamino) phenoxy) methyl) carbonyl-2-methyl-4 - '(4-fluorobenzyl) piperazine; NMR (DMSO-d6) 10.9 (d, 1), 9.5 (s, 1), 8. 1 (s, 1), 7 , 6 (d, 2), 7.3 (t, 2), 7.0 (m, 2), 5.0 (q, 2), 4.7 (m, 1), 4.3 (m, 2), 3.9-2.8 (m, 6), 2.1 (s, 3), 1.4 (d, 1.5), 1.3 (d, 1.5) ppm; ) -1- ((4-Chloro-2- (propylcarbonylamino) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) iperazine; NMR (DMSO-d 6) 9.5 (d, 1), 8.2 (s, 1), 7.8 (t, 2), 7.3 (t, 2), 7.0 (dt, 2), 6.8 (dq, 1), 6.4 (d, 1), 5.2-4.3- (m, 5), 3.9-2.8 (m, 5), 1.8 (d, 3), 1.3 (m, 6) ppm; (trans) -1- ((4-chloro-2- (iso-propylcarbonylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 9.5. (d, 1), 8. 2 (s, 1), 7.8 (t, 2), 7.3 (t, 2), 7.0 (m, 2), 5.2-4.3 ( m, 5), 3.9-2.7 (m, 6), 1.4-1.1 (m, 12) ppm; (trans) -1- ((4-chloro-2- (methoxymethylcarbonylamino) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 9.3 (s, 1), 8. 2 (s, l), -7.8 (t, 2), 7.3 (t, 2), 7.1 (m, 2 ), 5.3-4.2 (m, 5), 4.0 (s, 2), 3. 9-2.8 (m, 8), 1.4-1.2 (m, 6) ppm; (trans) -1- ((4-chloro-2- (2- (methoxycarbonyl) ethylcarbonylamino) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 9.5 (s 1), 8.1 (s, 1), 7.8 (t, 2), 7.3 (t, 2), 7.0 (m, 2) , 5.2-4.2 (m, 5), 3.8 (q, 1), 3.7-3.2 (m, 5), 2.9-6.6 (m, "6), 1.4-1.2 (m, 6) ppm; (trans) -1- ((4-chloro-2- (2- (ethoxycarbonyl) ethylcarbonylamino) phenoxy) methyl) carbonyl-2, 5-dimethyl- 4- (4-5 fluorobenzyl) piperazine; NMR (DMSO-d6) 9.6 (s.1), : 8.1 (s, 1), 7.8 (t, 2), 7.3 (t, 2), 7.0 (m, 2), .2-4.2 (m, 5), 4.0 (q, .2), 3.8 (q, 1), 3.6-3, -2 (m, 3), 2. 8- 2.6 (m, 5), 1.4-1.2 (m, 9) ppm; (trans) -1- ((4-chloro-2- (methylsulfonylamino) phenoxy) me-0-tyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-de) 10.9 (d, 1), 9. 3 (s.1), 7.7 (d, 2), 7.3-7.2 (m, 4), 7.0 ( d, 1), 5.0 (m, 2), 4.7 (m, 1), 4. 4 (m, 3), 3.9 (m, 1), 3.6 (m, 1), 3.4- 2.8 (m, 6), 1.4 (d, 1.5), 1.2 (d, 1.5) ppm; 5 (trans) -1- ((4-chloro-2- (bromomethylcarbonylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 10.0 (s.1), 8.4 (s, 1), 7.3 (ra, 2), 7.0 (m, 3), 6.9 (m, 1), 4 , 7 (ra, 3), 4.0 (s, 2), 3.8-3.1 (m, '5), 2.7 (dd, 1), 2.2 (d, 0 1), 1.3 (br d, 3), 1.0 (br s, 3) ppm; (trans) -1- ((4-chloro-2- (ethylcarbonylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 9.4 (s, 1), 8.5 (s, 1), 7.3 (m, 2), 7.0 (m, 3), 6, d '(d, 1), 4.7 (m, 3), 3.5 (m, 3), 3.1 (m, 2), 2.7 (dd, 1), 2.5 (q, 1), 2.2 (d) , 1), 1.3 (m, 6), 10 (m, 3) ppm; (trans) -1- ((4-chloro-2- (acetylaminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 8.0 (br s, 1), 7.3 (m, 3), 7.1 (dd, 1), 7.0 (m, 2), 6.8 (br d, .1 ), 4.7 (m, 3), 4.4 (d, 1), 3.8-3.0 (ra, 6), 2.7 (m, 1), 2.2 (m, 1) , '2', 0 (s, 3), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- (1- (methylsulfonyl) (methyl) aminoethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 4), 7.0 (t, 2), 6.8 (m, 1), 5.6 (q, 1), 4.7 (m, 3), 4 , 2 (m, 1), 3. 7 (m, 1), 3.5 (q, 2), 3.2 (m, 1), 3.1 (m, 1), 2.8 (d, 3), 2.7 (d, 3), 2.3 (br d, 1), 1.6 (d, 3), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- (1- (phenylsulfonyl) (methyl) aminoethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 7.6 (d, 2), 7.3 (m, 6), 6.9 (t, 2), -6.8 (t, 1), 5.6 (q, 1), A, 6 (m, 3), 4.2 (m, 1), 3.6 (m, 2), 3.4 (d, 1), 3.0 (m, 1), 2.6 (m, 4), 2. 4 (s, 3), 2.3 (m, 1), 1.3 (m, 6), 0.9 (m, 3) ppm; (trans) -1- ((4-Chloro-2- (1- (acetyl) (methyl) aminoethyl) phenoxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluoro-robinyl) piperazine; NMR (CDC13) 7.2 (m, 4), 7.0 (t, 2), 6.8 (m, 1), 6.0 '(m, 1), 5.4 (q, 1), 4.6 (m, 3), 4.2 (m, 1), 3.5 (q, 2), 3.2 (m, 1), 3.0 (m, 1), 2.6 (m, 4), 2. 2 (m, 3), 1.3 (m, 6), 0.9 (m, 3) ppm; (trans) -1- (2- (4-chlorophenyl) -3- (methylsulfonylamino) propyl) carbonyl-2,5-dimethyl-4- (-fluorobenzyl) piperazine; NMR (CDCl 3) 7.3 (t, A), 7.2 (br d, 2), 7.0 (t, 2)., 5.0 (br s, 1), 4.6 (br s, 1), 4.0 (m, 1), 3.4 (m, 5), 3.0 (m, 2), 2.8 (s, 3), .2.6 (m, 2), 2.2 (br d, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- (2- (4-chlorophenyl) -3- (acetylamino) propyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, A), 7.2 (br d, 2), 7.0 (t, 2), 5.2 (m, 1), 4.6 (br s, 1), 4.2 (m, 1), 3.8 (m, 1), 3.4 (m, 5) ,. 3.0 (m, 1), 2.8 (s, .3), 2.6 (m, 2), 2.2 (m, 1), 1.2 (m, 3), 0.9 ( m, 3) ppm; (trans) -1- (2- (4-chlorophenyl) -2- (methylsulfonylamino) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 5), 7.0 (t, 2), 6.6 (m, 1), 4.9 (q, 1), 4.6 (m, 0.5) , 4.2 (br d, 0.5), 3.8 (m, 1), 3.5 (m, i), 3.4 (m, 1), 3.0 (m, 2), 2 7 (m, 6), 2.2 (m, 1), 1.2 (m, 3), 0.8 (m, 3) ppm; (trans) -1- (2- (4-chlorophenyl) -2- (acetylamino) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.8 (m, 1), 7.3 (m, 5), 7.0 (t, 2), 5.3 (m, 1), 4.6 (m, 0.5), 4.1 (t, 0.5), 3.5 (m, 1), 3. 4 (m, 1), 3.0 (m, 3 ), 2, 6 (m, 2), 2.2 (m, 1), 2.0 (m, A), 1.2 (m, 3), 0.8 (m, 3) ppm; (trans) -1- ((4-chloro-2- ((4- (2,5-di (trifluoromethyl) phenylcarbonyl) piperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2, 5 -dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 11.0 (m, 1), 8.1 (m, 2), 7.9 (t, 1), 7.7. (m, 1), 7.4 (d, 1), 7.3 (m, 2), 7.2 (m, 1), 5.4 (m, 1), 5.0 (m, 2) , 4.4 (m, 6), 3.4 (m, 9), 3.0 (m, 1), 2.8 (m, 1), 1, 4 (m, 3), 1.2 ( m, 3) ppm; (trans) -1- ((4-chloro-2- ((4- (benzylcarbonyl) piperazin-1-yl) methyl) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-dd) 11.0 (m, 1), 7.9 (t, 2), 7.7. (t, 1), 7.6, (s, 1), 7.5 (d, 1), 7.3 (m, A), 7.2 (m, 3), 5.4 (m, 1 ), 5.0 (m, 2), 4.4 (m, 6), 3.7 (m, 2), 3.4 (m, 6), 3.0 (ra, 2), 2.8 (m, 1), 1.4 (dd, 3) , 1.2 (dd, 3) ppm; (trans) -1- ((4-chloro-2- ((A- ((2,3-, 4-trifluorophenyl) aminocarbonyl) piperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2 , 5-dimethyl-4- (4-fluorobenzyl) piperazine: NMR (DMSO-d 6) '11.0 (m, 1), 9.0 (s, 1), 7.9 (t, 2), 7 , 7. (m, 1), 7.6 (s, 1), 7.5 (m, 1), 7.2 (m, A), 5.4 (m, 5 1), 5.0 (m, ' 2), 4.4 (m, 6), 3.4 (m, 8), 3.1 (m, 2), 2.8 (m, 1), 1.4 (m, 3), 1.2 (m, 3) ppm; (trans) -1- ((4-chloro-2- ((4- ((2-fluorophenyl) aminocarbonyl) piperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4 -fluorobenzyl) piperazine; NMR (DMSO-0 d6). 11.0 (m, 1), 8.6 (s, 1), 7.9 (t, 2), 7.7. (m, 1), 7.6 (s, 1), 7.4 (d, 1), 7.3 (m, 1), 7.3 (t, 2), 7. 2 (m, 3), 5, 4 (m, 1), 5.0 (m, 2), 4.3 (m, '6), 3.4 (m, 9), 3.1 (m, 2), 2.8 (m, 1), 1.4 (dd, 3), '. 1.2 (dd, 3) ppm; 5 (trans) -1- (- (4-chloro-2 ^ ((N '- (2,6-difluorophenyl) ureido) phenoxy) methyl) carbonyl-2-, 5-dimethyl-4- (4-fluorobenzyl) piperazine; RM? (CDC13) 9.6 (br s, 1), 8.6 (s, 1), 7.4 (quin, 1), 7.3 (t, 2), 7.0 (m, 5), 6.9 (d, 1), 4.7 (m, 3), 4.1 (brs, 0.5), 3.8 (br s, 0.5), 3.5 (q , 2), 3.2 (m, 1), 3.0 (m, 1), 2.6 (dd, 1), 2.2 (d, 1), 1.2 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- (ethenylcarbonylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC1 3) 9.8 (d, 1), 8.6 (s, 1), 7.3 (m, 3), 7.0 (t, 3), 6.9 (d, 1), 6, 4 (dd, 2), 5.8 (dd, 1), 4.7 (m, 3), 3.6 (m, 1), 3.5 (q, 2), 3.2 (m , 1), 3.0 (m, 1), 2.7 (dd, 1), 2.2 (dd, 1), 1.3 fm, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- (cyclopropylcarboniland.no) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) pyrazinine; NMR (CDC'l3) 9.7 (br s, 1), 8.4 (s, 1), 7.3 (m, -2), 7.0 (ra, 3), 6.8 (d, 1), 4.7 (m, 3), 3.7 (m, 1), 3.5 (q, 2), 3.1 (m, 2), 2.7 (dd, 1), 2, 2 (dd, 1), 1.7 (m, 1), 1.3 (m, 3), 1.0 (m, 5), 0.8 (m, 2) ppm; (trans) -1- ((4-chloro-2- (cyclopentylcarbonylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR- (CDCi 3) 9.3 (br s, 1), 8.5 (s, 1), 7.3 (t, 2), 7.0- (m, 3), .6, 8 (d, 1), 4.7 (m, 3), 3.7 (m, 1), 3.5 (q, 2), 3.1 (m, 2), 2.8 (quin, 1), 2. 7 (dd, 1), 2/2 (dd, 1), 1.9 (m, 3), 1, 8 (m, 1), 1.6 (m, 3), 1.3 (m, 3), 0. 9 (m, 3) ppm; (trans) -1- ((4-chloro-2- ((furan-2-yl) carbonylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 10.4 (br s, 1), 9.7 (br d, 1), 8.2 (br s, 1), 7.9 (s, 1), 7.7 (m , 2), 7.3 (m, 3), 7.2 (s, 2), 6.7 (d, 1), 5.3 '(br d, 1), 5.0 (m, 2) , 4.7 (m, 0.5), 4.5 (m, 0.5), 4.2 (m, 3), 3. 6 (m, 1), 3.4 (m, 1), 2.8 (m, 1), 1.3 (m, 3), 1.2 (m, 3) ppm; (trans) -1- ((4-chloro-2- (phenylcarbonylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 10.0 (s, 1), 8.6 (s, 1), 8.1 (d, 2), 7.5 (m, 3), 7.3 (t, 2), 7 , 0 (t, 3 '), 6.8 (d, 1), 4.7 (m, 3), 37 (m, 1), "35 (q, 2), 3.1 (m, 2) , 2.7 (dd, 1), 2.2 (dd, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- (2- (4- chlorophenyl) -2- ((ethoxycarbonylmethylcarbonylamino) ethyl) carbonyl-2,5-dimethyl-4 -. (4-fluorobenzyl) piperazine; NMR (CDCl 3) 8.6 (m, 1), 7.2 (s, 6 ), '7.0 (t, 2), 5.4 (m, 1), 4.2 (q, 2), 3.8 (m, 1), 3.5 (m, 1), 3, 4 (m, 3), 3.0 (m, 3), - 2.6"(m, 2), 2.2 (m, 2), 1. 3. (m, 4.5), 1.1. (m, 1.5), 0.9 (dd, 1.5), 0.7 (dd, 1.5) ppm; (trans) -1- (2- (4-chlorophenyl) -2- (N '-iso-propylureido) ethyl ) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) pipe-, razine; RM? (CDCl 3) 7.3 (m, 6), 7.0 (t, 2), 5.2 (t , 1), 4.6 (m, 0.5), '4.4 (m, 1), 4.2 (t, 0.5), 3.8 (m, 1), 3.5 (m 1), 3.4 (ra, 1), 3.0 (m, 3), 2.6 (m, 1), 2.2 (m, .1), 1.1 (m, 9) , 0.9 (dd, 1.5), 0.8 (dd, 1.5) ppm; (trans) -1- (2- (4-chlorophenyl) -2- (N'- (2-chloroethyl) ureido) ethyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; RM (CDCl 3) 7.3 (m, 6), 7.0 (t, 2), 5.2 (t, 2), 4.6 (m, 0. 5), 4.2 (t, 0.5), 3.5 (m, 6), 3.0 (m, A), 2.6 (m, .1), 2.2 (m, l), 1.1 (m, 3) , 0. 9 (dd, 1.5), 0.8 (dd, 1.5) ppm; (trans) -1- (2- (4-chlorophenyl) -2- - ((2-nitrophenyl) carbonylamino) ethyl) carbonyl-2, 5-dimethyl-4 -. (4-fluorobenzyl) piperazine; RM? (CDC13) 8.1 (d, 1), 7.7 (q, -1), 7.6 (t, 2), 7.3 (m, 6), 7.0 (t, 2), 5.6 (m, 1), 4.6 (m, 0.5), 4.1 (t, 0.5), 3.7-3.2 (m, .3), 3.0 (m , 4), 2.6 (m, 1), 2.2 (m, 1), 1.2 (m, 3), 0.9 (m, 3) ppm; (trans) -1- (2- (4-chlorosphenyl) -2- ((4-methoxyphenylmethyl) carbonylamino) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; RM? (CDC13) 7.3 (m, 8), 7.0 (t, 2), 6.9 (d, 2), 5.3 (m, 1), 4.6 (m, 0.5), 4.1 (t, 0.5), 3.8 (s, 3), 3. 5 (m, 3), 3.4-2.8 (m, 6), 2.6 (m, 1), 2.2 (m, 1), 1.2 (m, 3), 0.8 (m, 3) ppm; (trans) -1- (2- (4-chlorophenyl) -2- ((2,4-dinitrofenyl) sulphonylamino) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 8.6 (s, 1), 8.2 (d, 1), 7.8 (m, 1), 7.3 (m, A), 7.0 (t, 2), 6 , 9 (t, 2), 5.0 (m, '1), 4.6 (m, 0.5), 4.1 (m, 0.5), 3. • 5 5 (m, 1) , 3.4 (m, 1), 3.0 (m, 5), 2.6 (m, 1), 2.2 (m, 1), 1.1 (m, 3), 0.8 ( m, 3) ppm; (trans) -1- (2- (4-chlorophenyl) -2- (cyclopropylcarbonylamino) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 7.3 (m, 6), 7.0 (t, 2), 5.2 0 (m, 1), 4.6 (m, 0.5), 4.2 (m, 0 , 5), 3.5 (m, 2), 3,4 (m, 1), 3.0 (m, 3), 26 (ra, 2), 2.2 (m, 1), 1.5 (m, 1), 1.2 (m, 3), 0 , 9 (m, 3.5), 0.7 (m, 3.5) ppm; (trans) -1- (2- (4-chlorophenyl) -2- ((2-cyclopropyl) yl) carbonylamino) ethyl) carbonyl-2,5-dimethyl-4- (4-5 fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 6), -7.0 (t, 2), 5.4 (m, 1), 4.6 (m 0.5), 4.2 (m, 0 ,5), 3.6 (m, 2), 3.4 (m, 1), 3. 0 (m, A), 2.6 (m, 1), 2.2 (m, 2), 1.6 (m , 10), 1.2 (m, 3), 1.1 (m, .2), 0. 8 (m, 3) ppm; 0 (trans) -1- (2- (4-chlorophenyl) -3- ((2-methylpropyl) carbonyl- • amino) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (d, 4), 7.2 (d, 2), 7.0 (t, 2), 6.0 (br s, 1), '4.6 (m, 0, 5), 4.2 (m, 0.5), '3.6 (m, -2), 3.4 (m, 3), 3. 0 (m, 2), 2.6 (m, 3 ), 2.2 (d, 1), 2.0 (m, A), 1.2 (m, 3), 0.9 (m, 9) ppm; (trans) -1- (2- (4-chlorophenyl) -3- (cyclopentylcarbonylamino) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 7.3 (d, 4), 7.2 (d, 2), 7.0 (t, 2-), 6.0 (br s, 1), 4.6 (m, 0.5), 4.2 (m, 0.5), 3.6 (m, 2), 3.4 (m, 3), 3.0 - (m, 2), 2.6 (m, 3), 2.4 (m, 1), 2/2 (d, 1), 1,6 (m, 8), 1,1. (m, A), 0.9 (m, 4) ppm; (trans) -1- (2- (4-chlorophenyl) -3- (N '- (t-butyl) ureido) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; RM? (CDC13) 7.3 (d, 4), 7.2 (d, '2), 7.0 (t, 2), 4.6 (m, 1.5), 4.2 (m, 0, 5), 3.6 (m, 2), - 3.4 (m, A), 3.2 (m, 1), 3.0 (m, 1), 2. 6 (m, -2), 2.2 (d, 1) ,. 1.3 (s, 9), 1.2 (m, 3), 0.9 (m, 3) ppm; (trans) -1- (2- (4-chlorophenyl) -3- (N '- (ethyl) ureido) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; RM? (CDCl 3) 7.3 (d, A), 7.2 (d, 2), 7.0 (t, 2), 5.1 (m, 1), 4.9 (m, 1), 4.6 (m, 0.5), 4.2 (m, 0.5), '3.6 (m, 2), 3.4 (m, 4), 3.2 (m, 3), 3.0 (m, 1), 2.6 (m, 3), 2.2 (m, 1), 1.1 (m, 6) 0.9 (m, 3) ppm; (trans) -1- (2- (4-chlorophenyl) -3- (N '- (3-choropropyl) ureido) propyl) carbonyl-2, 5-dimethyl-4- (4'-fluorobenzyl) piperazine; NMR (CDCl 3) 7.3 (d, 4), 7.2 (d, 2), 7.0 (t, 2), 5.6 (br s, 1), 5.9 (s, 1), 5 4.6 (m, 0.5), 4 , 2 (m, 0.5), 3.6 (m, 5), 3.4 (m, 5), 3.2 (m, 1), 3. 0 (m, 1), 2.6 (m, 3), 2.2 (d, 1), 2.0 (t, 2), 1.2 (m , 3), 0.9 (m, 3) 'ppm; (trans) -1- (2- (4-chlorophenyl) -3- ((morpholin-4-yl) carbonylamino) propyl) carbonyl-2,5-dimethyl-4- (4-fluoroben-0yl) piperazine; NMR (CDC13) 7.3 - (d, 4), 7.2 (d, 2), 7.0. (t, 2), 5.8 (br d, 1), 4.6 (m, 0.5), 4.2 (m, 0.5), 3.6 (m, 6), 3.4 (m, A), 3.3 (t, 4), 3.0 (m, 2), 2.6 (m, 3), 2.2 (m, 1), 1.2 (m, 3) 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- ((N '- (methoxycarbonylmethylcarbonyl) -N' - (methyl) glycinamide) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (-fluorobenzyl) ) piperazine; RM? (CDC13) "9.6 (br s, 1), 8. 4 (d, 1), 7.3 (dd, 2), 7.0 (t, 3), 6.8 ( d, 1), 4.7 (m, 3), 4.3 (s, 2), 3. 8 (s, 3), 3.6 (m, A), 3.5 (m, 2), 3.1 (m, A), 2.7 (dd, 1), 2.2 (d, 1), 1. 3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- ((N '- (2-methoxycarbonylethyl) carbonyl-N' - (methyl) glycinamide) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4 -fluorobenzyl) piperazine; NMR (CDCl 3) 9.6 (br s, 1), 8.4 (d, 1), 7.3 (dd, 2), 7.0 (t, 3), 6.8 ( d, 1), 4.7 (m, 3), 4.3 (s, 3), 3.8 (s, 3), 3.6 (q, 2), 3.2 (s, 3), 3.1 (s, 2), 2.7 (m, 5), 2.2 (d, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) - 1- ((4-chloro-2- ((N '- (3-methylbenzyl) aminocarbonyl-N' - (methyl) glycinamide) phenoxy) methyl) carbonyl-2,5-. Dimethyl-4- (4- fluorobenzyl) piperazine; RM (CDCl 3) 9. 6 (br s, 1), 8.4 (d, 1), 7.3 (dd, 2), 7.2 (t, 1), 7.0 ( m, 6), 6.8 (d, 1), 5. 4 (t, 1), 4.6 (m, 3), 4.4 (d, 2), 4.3 (s, 2), 3.8 (m, 1), 3.5. (q, 2), 3. 1 (m, 5), 2.6 (m, 1), 2.3 (s, 3) ", 2.2 (d, 1), 1.3 (m, 3 ), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- ((N '- (3-trifluoromethyl-4-fluorophenyl) carbonyl-N'- (methyl) glycine (mido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; RM (CDCl 3) 9.8 (br s, 1), 8.4 (d, 1), 8 , 1 (br s, 1), 7.6 (m, 2), 7.3 (dd, 2), 7.0 (m, A), 6.8 (d, 1), 4.7 (m , 3), 4.3 (t, 2), 3.7 (m, 1), 3.6 (q, 2), 3.2 (s, 3), 3.1 (m, 2), 2 , 7 (m, 1), 2.2 (d, 1), 1.3 (m, 3), 0. 9 (m, 3) ppm; (trans) -1- ((A-chloro-2- ((N '- (4-methylbenzyl) aminocarbonyl-N' - (methyl) glycinamide) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 9.6 (br s, l), 8.4 (d, 1), 7.3 (m, 2), 7.2 (d, 2), 7, 1 (d, 2), 7.0 (m, 3), 6.8 (d, 1), 5.4 (t, '' 1), 4.7 (m, 3), 4, 4 (d , 2), 4.2 (d, 2), 3.8 (m, 1), -5 3.6 (q, 2), 3.1 (m, 5), 2.7 (ra, 1) , 2.3 (s, 3), 2.2 (d, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro- 2- ((N '- (3-chlorophenyl) carbonyl-N' - (methyl) glycinamide) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; RM (CDCl 3); 9.9 10 (br s, 1), 8.4 (d, 1), 7.5 (s, 1), 7.3 (m, 5), 7.0 '; (t, 3), 6.8 (d, 1), 4.7 (m, 3), 4.4 (br s, 2), 4.1 (m, 1), '3.6 (m, 1), 3.5 (q, 2), 3.2 (m, 3), 3.0 (m, 1), 2.7 (dd, 1 ), 2.2 (d, 1), 1.3 (ra, 3), 0.9 (m, 3) ppm; 5 (trans) -1- ((A-chloro-2- ((N '- (4-fluorobenzyl) aminocarbonyl-N' - (methyl) glycinamide) phenoxy) -methyl) carbonyl-2, 5-dimethyl- 4 -. (4-fluorobenzyl) piperazine; RM? (CDCl 3) 9.7 (br s, 1), 8.4 (s, 1), 7.3 (m, 4), 7.0 (m, 5), 6.8 (d, 1), 5.5 (t, 1), 4.7 (m, 2) 4.4 (d, 2), 0 4.2 (m, 2), 3, 6 (m, 1), 3.5 (q, 2), 3.1 (m, 5), 2.7 (m, 1), 2.2 (d, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-Cioro-2- (N '- (methoxymethylcarbonyl) glycinamide) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 10.1 (br s, 1), 8.4 (d, 1), 7. 3 (t, 3), 7.0 (t, 3), 6.8 (d, 1), 4.7 (m, 3), 4.2 (d, 2), 4.0 (s, 2), 3.6 (m, 1), 3.5 (q, 2), 3.4 (s) , 3), 3.1 (m, 2), 2.7 (dd, 1), 2.2 (d, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- (N '-. (ethoxycarbonylaminocarbonyl) glycinamide) phenoxy) methyl) carbonyl-2,5-dimethyl-' 4- (4-fluorobenzyl) piperazine; RM? (CDCl 3) 9. 9 (br s, 1), 8.4 (m, 2), 7.3 (m, 3), .7.0 (m, 3), 6.8 (d, 1), 4.7 (m, 3), 4. 4 (m, 6), 3.6 (m, 1), 3.5 (q, 2), 3.1 (m, 2), 2.7 (dd, 1), 2.2 (d, 1), 1.3 (m, 6), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- (N '- (2-iodophenylcarbonyl) glycine) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; RM? (CDCl 3) 10. 4 (br s, 1), 8.4 (d, 1), "7.9 (d, 1), 7.5 '(d, 1), 7.4 (t, 1) , 7.3 (m, 2), 7.1 (t, 1), 7.0 (t, 3), 6.8 (m, 2), 4. 7 (m, 3), 4.4 ( d, 2), 3.6 (m, 1), 3.5 (q, 2), 3.1 (m, 2), 2.7 (dd, 1), 2. 2 (d, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- (N '- (2,3-difluorophenylcarbonyl) glycinamide) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC1 3) 10.3 (br s, 1), 8.4 (d, 1), 7.8 (t, 1), 7.5 (quin, 1), 7.3 (m, 3) , 7.2 (m, 1), 7, Q (t, 3), 6.8 (d, 1), 4.7 (m, 3), 4.4 (d, 2), 36 (m, 1), 3.5 (q, 2), 3.1 (m, 2), -5 2.7 (dd, 1), 2.2 (d, 1), 1.3 (m, 3), 0. 9 (m, 3) ppm; (trans) -1- ((4-chloro-2- (N '- ((4-phenoxyphenyl) aminocarbonyl) glycinamide) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine-; RM? (CDCI3) 9.9 10 (br s, 1), 8.3 (br s, 1), 7.3 (m, 6), 7.0 (t, 6), 6.8 (m, 3), 6.5 (m, 1), 4.7 (m, 3), 4.4 (m, 2), 3.6 (m, 1), 3.5 (q , 2), 3.1 (m, 2), 2.7 (dd, 1), 2.2 (d, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -l- ((A-chloro-2- (N'- (2,4-diflurophenylcarbo-5-nyl) glycinamide) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) ) piperazine; RM? (CDC13) 10.3 (br s, 1), 8.4 (d, 1), 8.1 (q, 1), 7.5 (m, 1), 7. 3 (m, 2), 7 , 0 (t, 3), 6.8 (m, 3), 4.7 (m, 3), 4.4 (d, 2), 3.6 (ra, 1), 3.5 (q, 2), 3.1 (m, 2), 2.7 0 (dd, 1), 2.2 (d, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ("(4-chloro-2- ((2-iodophenylcarbonyl) aminomethyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; RM (CDCl 3) , 0 (m, 1), 7.8 (d, 1), 7.3 (m, 5), - 7.2 (dd, 1), 7.0 (m, 3), 6. 8 (d, 1), 4.8 (m, 3), 4.6 (d, 2), 4.4 (m, 0.5), 3. 9 (m, 0.5), 3.5 (q, 2), 3.1 (m, 2), 2.6 (m, 1), 2.2 (m, 1), 1.3 (m , 3), 0.9 (m, 3) ppm; (trans) -1- ((A-chloro-2- ((ethoxycarbonylmethylcarbonyl) aminomethyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 8. 4 (br s, 1), 7.3 (m, 3), 7.2 (dd, 1), 7.0 (m, 2), 6.8 (d, • 1) , 4.8 (m, 3), 4. 5 (d, 2), 4.2 (m, 3), 3.6 (m, 1), 3.5 (q, 2), 3.3 ( s, 2), 3.1 (m, 1), 2. 6 (m, 1), 2.2 (d, 1), 1.3 (m, 6), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- (N '- (3-chloropropyl) ureidomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; RM? (CDC13) 7.3 (ra, 3), 7.2 (dd, 1), 7.0 '(m, 2), 6.8 (d, 1), 4.8 (m, A), 4, -4 (d, 2), -4.2 (m, 1), 3.6 (m, 5), 3.3 (m, 3), 3.1 (m, 1), 2.6 (m, 1), 2. 2 (d, 1), 1.9 (quin, 2), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- (N '- (2-fluoro-6-trifluoromethylphenyl) ureidomethyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) ) piperazine; RM? (CDC13). 8.2 (m, 1), 7.3 (m, 6), 7.2 (dd, 1), 7.0 (t, 2), 6.8 (d, 1), 4.8 (m , 3), 4.4 (d, 2), 3.8 (m, 1), 3.5 (q, 2), 3.2 (m, 1), 3.1 (m, 1), 2 , 6 (m, 1), '2.2 (m, 1), 1. 3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- ((3-fluorophenyl) carbonylaminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluoro-benzyl) piperazine; NMR (CDC13) 8.6 (m, 1), 7.8 (t, 2), 7.3 (m, A), 7.2 (dd, 1), 7.1 (dt, 1), 7.0 (t, 2) > 6.8 (d, 1), 4.8 (m, 3), 4.6 (d, 2), 3.8 (m, 1), 3.5 (q, 2), 31 (m, 2 ), 2.6 (m, 1), 2.2 (d, 1), 1. 3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((A-Cloxo-2- (N '- (2- (ethoxycarbonyl) ethyl) ureidomethyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 3), 7, -2 (dd, 1), 7.0 (t, 2), 6.9 (m, 1), 6.8 (d, 1), 5.1 (m, 1), 4.8 (m, 3), 4.4 (d, 2), 4.1 (q, 2), 3.6 (m, 2), 3.4 (m , 3), 3.2 (m, 1), 3. 1 (m, 2), 2.7 (ra, 1), 2.5 (t, 2), 2.2 (d, 1), 1.3 (m, 6), 0.9 (m, -3) - ppm; (trans) -1- ((4-chloro-2- ((2,5-di (trifluoromethyl) phenyl) carbonylaminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 8.9 (m, 1), 7.8 (m, 2), 7.2 (s, 1), '7.3 (m, 3), 7.2 (dd, 1), 7.0 (t, 2 ), 6.8 (d, 1), 4.8 (m, 3), 4.6 (d, 2), 4.4 (m, 0.5), 3.9 (m, 0.5) , 3.5 (q, 2), 3.1 (m, 2), 2. 6 (m, 1), 2.2 (m, 1), 1.3 (m, 3), 0.9 ( m, 3) ppm; and (trans) -1- ((4-chloro-2- (N '- (2- (phenyl) cyclopropyl) ureidomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; RM? (CDC13) 7.3 (m, 8), 7.0 (m, 3), '6.8 (d, 1), 4.9 (s, 1), 4.6 (d, 2), 4.4 (m, 2), 3 , 8 (m, 1), 3.5 (q, 2), 3.2 (m, 1), 3.0 (m, 1), 2.7 (m, 2), 2. 2. (m , 1), 2.0 '(m, 1), 1.3 (m, 5), 0.9 (m, 3) ppm. 0 G. In a similar manner, the following compounds of formula (Ib) were prepared: 1- (2- (4-chlorophenyl) ethenyl) carbonyl-4- (4-fluorobenzyl) piperazine; 1- (2- (4-chlorophenyl) ethyl) carbonyl-4- (4-fluoroben--5-cyl) piperazine; 1- (1- (t-butoxycarbonyl) amino-2- (4-chlorophenyl) ethyl) carbonyl-4- (benzyl) piperazine; 1- (3- (t-butoxycarbonyl) amino-2- (4-chlorophenyl) propyl) carbonyl-4- (4-fluorobenzyl) piperazine; RM? (CDCl 3) 7.2 (m, 8), 4.8 (m, 1), 3.6-3.3 (m, 8), 2.6 (m, 2), 2. 3 (ni, 3), 2.1 (m, 1), 1.4 (s, 9) ppm; 1- (2- (3, 4, 5-trimethoxyphenyl) ethenyl) carbonyl-4- (4-fluorobenzyl) piperazine; RM? (CDC13) 7.6 (d, 1), 7.3 (m, 4), 6.7 (m, 3), 3.9-3.6 (m, 13), 3. "5 (s, 2), 2.5 (m, 4) ppm; 1- (1- (3,4-dimethoxyphenyl) -2- (4-chlorophenyl) ethenyl) carbonyl-4- (4-chlorobenzyl) piperazine; (2- (3, 4, 5-trimethoxyphenyl) ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((acetyl) amino) (4-chlorophenyl) methyl) carbonyl-4- (4-fluorobenzyl) piperazine, hydrochloride salt EXAMPLE 2 Compounds of Formula (Ia) A. To a solution of (2R, 55) -1- (chloro) acetyl-4- (4-fluorobenzyl) -2,5-dimethylpiperazine (0.29 g , 1 mmol) in anhydrous DMF (5 mL) was added 4-hydroxy-3-methoxyphenylacetonyl ilo (0.20 g, 1.2 mmol) and potassium carbonate (0.28 g, 2 mmol, powder). The resulting mixture was stirred at 50 ° C. After 15 hours analysis by analytical HPLC (HPLC on a vydac column of C18 with 20-70% acetonitrile in gradient water with 0.1% trifluoroacetic acid) showed that it had been produced. The total consumption of starting material The mixture was poured into water and extracted with three portions of ethyl acetate. The combined organic extracts were washed consecutively with 0.5 N aqueous KOH solution, water, then brine. It was then dried over MgSO4, filtered and concentrated in vacuo to give a yellow oil. This was dissolved in ethyl acetate and treated with a solution of HCl in anhydrous ether. Filtering the resulting solid gave 0.38 g (85% yield) of (2R, 55) -1- ((4- (cyano) methyl-2-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) -2,5-dimethylpiperazine, hydrochloric acid salt as a white solid: NMR (DMSO- d6) 11.5 (br s) , 1), 7.6 (m, 4), 6.9 (m, 3), 4.8 (br s, 2), 4.4 (br s, 3), 4.0 (m, 1) ', 3.9 (s, 2), 3.8 (s, 3), 3.6 (m, 1), 3.3 (m, 2), 3. 2-2.9 • (m, 3 ) ppm. similarly, other compounds of formula (la) were prepared: (trans) -1- ((4-fluoro-3-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4- fluorobenezy) piperazine; NMR (DMSO-de) 10.4 (br d, 1), 7.7 (m, 2), 7.2 (m, 4), 6.9 (br s, 1), 5.0 (m, 1), 4.8 (m, 2), 4.3 (m, 3), 3. 7 (m, 2), 3.3 (m, 2), 2.9 (m, 1), 1, 4-1.2 (m, 6) ppm; 1- ((2-acetylaminophenoxy) methyl) carbonyl-4- (4-fluorobenzyl) piperazine; 'NMR (DMSO-d6) 10-, 6 (br s, 1), 9.4 (s, 1), 8.0 (d, 1), 7.8 (br s, 2), 7.2' (t, 2), 6.9 (m, 3), 5.0 (m, 3), 4.3 (m, 3), 3.8 (q, 1), 3. 6 (br s, 1 ), 3. 4 (m, 1), 2.8 (m, 1), 2.1 (s, 3), 1.3 (dd, 3), 1.2 (d, 3) ppm; 1- ((3, 4, 5-trimethoxyphenoxy) methyl) carbonyl-2- (methoxycarbonyl) methyl-4- (4-fluorobenzyl) piperazine; • 5- ((3,4,5-trimethoxyphenoxy) methyl) carbohyl-2- (ethoxycarbonyl) -4- (4-fluorobenzyl) piperazine; (cis) -1- ((3, 4, 5-trimethoxyphenoxy) methyl) carbonyl-2,6-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 2), 7.0 (t, 2), 6.2 (s, 2), 4.7-4. 2 (m, A), 0 3.8 (m, 9), 3.5 (s, 2), 2.6 (d, 2), 2.2 (dd, 2), 1.3 (m, 6) ppm; 1- ((3, 4, 5-trimethoxyphenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 2), 7.0 (t, 2), 6.2 (s, 2), 4.6 (s, 3 '), 4.4 (m, 1), 4.1 (m, 1), 3.8 (-3, -6), 3.85 (s, 3), 3.5 (m, 2), 2.8 (d, -1), 2.6- (d, 1), 2.1 (m, 2), 1.3 (m, 3) ppm; 1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.6 (s, 2), 4.4 (m, 1), 4 , 1 (m, 1), 3.7 (m, 1), 3.4 (.m, 2), - 2.8 (m, 1), 2. 6 (d, 1), 2.0 (m, 2), '1.3 (m, 3) ppm; 1- ((4-chlorophenoxy) methyl) carbonyl-3-methyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.6 (s, 2), 4.0 (m, 2), 3.7 (m, 1), 3.4-2.9 (m, 3), 2.7 (m, 1), 2.5 (m, 1), 2. 1 (-m, 1), 1.1 (m, 3) ppm; (2S) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (2R) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine-; NMR (CDC13) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.6 (s, 2), 4.4 (m, 1), 4.1 (m, 1), 3.7 (m, '1), 3.4 (m, 2), 2.8 (m, 1), 2.6 (d, 1), 2.0 (m, 2 ), 1.3 (m, 3) 'ppm; 4- ((4-chiorophenoxy) methyl) carbonyl-3- (((4-chlorophenyl) amino) carbonyl) methyl-1- (benzyl) piperazin-2-one; 1- ((phenoxy) methyl) carbonyl-2-ethyl-4- (4-fluorobenzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-2-hydroxymethyl-4- (4-fluorobenzyl) piperazine; - NMR (CDC13) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.7-4.5 (m, 3), 4.2-3 , 3 (m, 5), 3.2-2.7 (m, 2), 2. 3- 2.0 (m, '4) ppm; 1- (1- (4-chlorophenoxy) -1-methylethyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (25, 5R) -1- ((4-chloro-3,5-dimethoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 7.3 (m, 2), 7.0 (t, 2), 6.2 (s, 2), 4.6 (m, 34), 4.2 (m, 1), 3 , 8 (m, 6), 3.5 (m, 3), 3.0 (m, 1), 2.7 (dd, 1), 2.2 (d, 1), 1.3 (m, A), 0.9 (m, 3) ppm; (2R, 5S) -1- ((4-chloro-3,5-dimethoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 2), 7.0 (t, 2), 6.2 (s, 2), 4.6 (m, 3), 4.2 (m, 1), 3, 8 (m, 6), 3. 5 (m, 3), 3.0 (m, 1), 2.7 (dd, 1), 2.2 (d, 1), 1.3 (m, 3 ), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-3,5-dimethoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 7.3 (m, 2), 7.0 (t, 2), 6.3 (s, 2), 4.7 (m, 2), 4.2 (m, 1), 3 , 8 (s, 6), 3.5 (ra, A), 3.0 (m, 1), 2.7 (dd, 1), 2.2 (d, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; (25, 5R) -1- ((4-bromo-3,5-dimethoxy-noxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, hydrochloride salt; NMR (DMSO-d6) 10.7 (d, 1), 7.8 (m, 2), 7.3 (m, 2), 6.3 (s, 2), 4.9 (m, 2) , 4.3 (m, 2), 4.0-2.8 (ra, 12), 1.4-1.2 (m, 6) ppm; (25, 5R) -1- ((4-nitro-3-formylphenoxy) methyl) carbonyl-2,5-diraethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 10.4 (s, 1), 8.2 (d, 1), 7.3 (m, 4), 7.0 (t, 2), 4.8 (m, 3), 4 , 2-2.3 (m, 7), 1.3"(m 3), 1.0 (m, 3) ppm; (trans) -1- ((4-chloro-2- (aminocarbonyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 9.2 (br s, 1), 8. 2 (s, 1), 7.4 (m, .3), 7.0 (t, 2), 6.8 (d, 1), 5.9 (s, 1), 5.0-4.0 (m, 3), 3. 8-3.0 (m, 5), 2.8 (d, 1), 2.3 (d, 1), 1.3 (m, 3), 1.0 (br s, 3) ppm; (2R, 55) -1- ((4-chloro-2- (aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 9.2 (br s, 1), 8.2 (s, 1), 7.4 (m, A), 7.0 (t, 2), 6.8 (d, 1) , 5.8 (s, 1), 4.7 (m, 2), 3.7-3.1 (m, 5), 2.8 (d, 1), 2.3 (d, 1), 1. 3 (d, 3), 1.0 (br s, 3) ppm; (2R, 55) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5- - - ((amino) carbonyloxy) methyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-3-nitrophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, hydrochloride salt; NMR (DMSO-d6) 11 (br d, 1), 7.9 (br s, 1), 7.6 (m, 2), 7.3 (ra, 4), 5.2 (d, 1), 5.0 (m, 2), 4.3 (m, A), A. 0 (m, 1), 3.6 (m, 2), 1.3 (m, 6) ppm; (trans) -1- ((A- _ chloro-2- (hydroxymethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine, hydrochloride salt; NMR (DMSO-d 6) 10.9 (br d, 1), 7.9 (br s, 2), -7.6 (m, 1), 7.3 (m, A), 5.0 ( m, 2), 4.5 • 5 (s, 2), 4.3 (m, 2), 3.7-3.3 (m, 6), 1.3 (m, 6) ppm; (trans) -1- ((4-chloro-2-aminophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, dihydrochloride salt; NMR (DMSO-d 6) 7.7 (br s, 3), 7.3 (m, 5), 5.2 (d, 1), 5.0 (m, 2), 47-4.2 ( m, 4), 3.9-3.4 0 (m, 3), 1.3 (m, .6) ppm; (trans) -1- ((2- (aminocarbonyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine (R) NMR (CDC13) 9.1 (br s, 1), 8.2 (d, 1), 7.4 (dd, 1), 7. 3 (br s, 2), 7.1 (t, 1), 7.0 (m, 2), 6.9 (d, 1 ), 5 5.8 (br s, 1), 4.7 (m, 2), 4.2 (m, 1), 3.7-3.4"(m, 3), - 3.0 (br s, 1), 2.7 (br s, 1), 2.3 (d, 1), 1. 3 (m, 3), 1.0 (m, 3) ppm; (trans) -1- ((4-chloro-2-amino-5-nitrophenoxy) methyl) carb.o-nil-2,5-dimethyl-4- (4-fluorobenzyl) piperazine, salt or dihydrochloride; NMR (CDCl 3) 10.9 (br d, 1), 7.8 (m, 2), 7.5- (dd, 1), 7.3 (m, 2), 6.8 (s, 1), 5.0 (m, 3), 4.3-3.2 (m, 7), 1.4-1.2 (m, 6) ppm; (trans) -1- ((4-methyl-2-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine, hydrochloride salt; NMR (DMSO-d6) 10.9 (br d, 1), 10.4 (s, 1), 7.9 (s, 2), 7.5 (m, 2), 7.3 (m, 2 ), 7.0 (d, 1), 5.2 (m, 1), 5.0 (m, 2), 4, 6 (m, 1), 4.3 (m, 3), 3.6 (m, 2), 2.8 (m, 1), 2.5 (s, 3), 1.4-1.1 (m, 6) ppm; (trans) -1- ((4-chloro-2-formylphenoxy) methyl) carbonyl-2,5-. dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 10.9 (br d, 1), 10.4 (s, 1), 7.8- (s, 1), 7.5 (dd, 1), 7.3 (dd, 2) , 7.0 (m, 3), 4, -8 (m, 3), 4.1 (m, 1), 3.5 (m, 3), 3.0 (br s, 1), 2, 7 (dd, 1), 2. 5 (d, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((2-methylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine hydrochloride salt; NMR (DMSO-de) 11.0 (d, 1), 7.8 (t, 2), 7.3 (t, 2), 7.1 (m, 2), 6.8 (m, 2 ' ), 4.9-3.3 (m, 9), 2.8 (t, 1), 2.2 (s, 3), 1.4-1.1 (m, '6) ppm; (trans) -1- ((2- (hydroxymethyl) -phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine, hydrochloride salt; NMR (DMSO-d6) 11.0 (d, 1), 7.8 (t, 2), 7.3 (m, 3), 7.1 '(t, 1), 6.9 (m, 2 ), 5.0-3.2 (m, 11), 2.8 (t, 1), 1.4-1.1 (m, 6) 'ppm; (trans) -1- ((3-chloro-5-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine, hydrochloride salt; NMR (DMSO-d6) 10.8 (d, 1), 7.8 (m, 2), 7.3 (t, 2), 6.6 (s, 2), 6.5 (br s, 1 ), 5.0-3.2 (m, 12), 2.8 (m, 1), 1.4-1.2 (m, 6) ppm; (trans) -1- ((2-methoxy-5-nitrophenoxy) methyl) carbonyl-2,5-, 5-dimethyl-4- (4-fluorobenzyl) piperazine, hydrochloride salt; NMR (DMSO-d6) 11.1 (d, 1), -7.9 (m, 2), 7.7 '(br s, 1), 7.2 (m, 4), 5.2-3 , 3 (m, 12), 2.8 (t, 1), 1.4-1.2 (m, 6) ppm; 1- ((phenoxy) methyl) carbonyl-2-methyl-4- (4-fluoroben-0yl) piperazine; NMR (DMSO-d6) 11 (br d, 1), 7.7 (m, 2), 7.3 (m, 4), 6.9 (m, 3), 4. -9 (m, 3), 4.3 (m, 3), 4.0-2.8 (m, 5), 1.4 (d, 1.5), 1.2 (d, 'l, 5) ppm; (trans) -1- ((4-chlorophenylamine) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6). 5 7.4 (dd, 2), 7.1- (m, 4), 6, 6 (d, 2), 5.8 (t, 1), - 4.5 (br s, 0.5), 4.0 (br m, 1.5), 3.8 (br m, 1), 3.8-3.3 (m, 3), 3, 0 (m, 2), 2.6 (m, 1), 2.2 (d, 1), 1.1 (br d, 3), 0.9 (br d, 3) ppm; (trans) -1- ((4-chloro-3-nitrophenoxy) methyl) carbonyl-2-0 methyl-4- (4-fluorobenzyl) piperazine; NMR (DMS0-d6) 11 (br d, 1), _ 7.7 (m, - A), 7.3 (m, 3), 5.0 (q, 2), 4.7 (m, 0.5), 4, 4 (m 2.5), 3.8 (ra, 0.5), 3.6-2.9 (ra, 6), 1.4 (d, 1.5), 1. 3 (d. , 1.5) 'ppm; (trans) -1- ((4-chloro-2-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 10.8 (br d, 1), 7.9-6.8 (m, 7), 5.1-2.8 (m, 10), 2. 2 (s, 3), 1.3 (m, 6) ppm; (trans) -1- ((4-chloro-2- (diethylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 2), 7.0 (t, 2), 6.8 (m, 3), 4.8 (br s, 3) -. 4.1 (br s, 1), 3.5 (q, 3), 3.2 (q, 4), 3.0 (br s, 1), 2.7 (dd, 1), 2.2 (d, 1), 1.3 (br s, 3), -1 (m.9) ppm; (trans) -1- ((4-chloro-2-hydroxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7. 3 (m, 2), 7. 0-6.7 (m, 5), 4.9 (ra, 0.5), 4.6 (br s, 2), 4.2 (m, 0.5 ), 3.6-3.2 (m, 3), 3.0 (br d, 1)., 2.7 (br d, 1), 2.2 (d, 2), 1.3 (m , 3), 0.9 (m, 3) ppm; 1- ((4-chloro-2- (hydroxymethyl) phenoxy) methyl) .carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) .8 (d, .1), 7.7 (m, 2), 7.3 (m, 4), 6.9 (d, 1), 5.0-4.3 (m, 6), 3.9-2.9 (m, 7), 1.4 (d, 1.5), 1.2 (d, 1.5) ppm; (2J, 55) -1- ((4-chloro-3- (hydroxymethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, A), 7.0-6.7 (m, 3), 4. 7 (m, A), 4.1 (m, 1), 3.5 (m, 2.5), 3.2 (m, 0.5), 3.0 (s, 1), 2.7 (dd, 1), 2.2 (d, 1), 2.1 (, 1) , 1.2 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- (ureidomethyl) phenoxy) methyl) carbonane-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 7.4 (m, 2), 7.1 (m, 4), 6.9 (d, 1), 6.4 (t, 1), 5.6 (s, 2) , 5.0-4.0 (m, 4),. 3.5 (m, 2), 3.3 (d, 2), 3.0 (m, 2), 2.2 (m, 2), 1.2 (br d, 3), 0.9 ( br d, 3) ppm; 1- ((4-chloro-2-aminophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 11.2 (br d, 1), 7.7 (m, 2), 7.3 (t, 2), 6.9 (m, 3), 5.0-4.2 (m, 5), 3.9 (m, 1), 3. 6 (m, 1), 3.4 (m, 1), 3.0 (ra, 3), 1.4 (d, 1, 5), 1.3 (d, 1.5) ppm; 1- ((4-chloro-3-aminophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 11.2 (br d, 1), 7.8 (br s, 2), 7.3 (t, 2), 7.0 (d, 1), 6.4 (s, 1), 6.2 (d, 1), 4.8-4.2 (m, 5), 4.0 (m, 1), 3.6 (m, 1), 3.4 (d, 1), 3.2-2.9 '(m, 4), 1.3 (m, 3) ppm; (25) -1- ((4-chloro-2- (ureido) phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 9. 0 (s, 1), 8.2 (s, 1), 7.3 (t, 1), 7.0 (t, 3.), 6.8 (q, 3), 5.0 (s, 2), 4.6 (dt, 2), 4.4 (d, 0.5), 3.7 (br s, 0.5), 3.4 (m, 2.5 ), 3.0 (t, 0.5), 2.8 (m, 1), 2.6 (d, 1), 2.1 (m, 3), 1.4 (d, 1.5) , 1.3 (d, 1.5) ppm; 5 (2R) -1- ((4-chloro-2- (ureido) phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 9.0 (s, 1), 8.2 (s, 1), 7.3 (t, 1), 7/0 (t, 3-), 6.8 (q, 3), 5.0 (s, 2), 4.6 (dt, 2), 4.4 (d, 0.5), 3.7 (br s, 0.5), 3.4 (m, 2, 5), 3.0 (t, 0.5), 2.8 (m, 1), 2.6 (d, 1), 2.1 (m, 3), 1.4 (d, 1.5), 1.3 (d, 1.5) ppm; (trans) -1- ((4-chloro-2- (ureido) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 10.8 (br s, 1), 8.2 (br s, 2), 7.8 (br s, 1.5 2), 7.7 (br s, 1) -, 7, 3 (m, 2), 6.8 (br s, 2), 5.2- 4.3 (m, 5), 3.9-3.1 (m, 5), 2.8 (t, 1 ), 1.5-1.1 (m, 6) ppm; (2R, 55) -1- ((4-chloro-2- (ureido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR 0 (CDC13) 9. 0 (s, 1), 8.3 (s, 1), 7.3 (t, 1), 7.0 (t, 3), 6.8 (m, 3), 5.0 (s, 2), 4.6 (m, 2), 4.2 (d, 0.5), 3.7-3.4 (m, 2.5), 3.2 (ra, 2), 2.7 (d, 1), 2.5 (m, 1), 2.2 (d, 1), 1.3 (br d, 3), 1.0 (br d, 3) ppm; (trans) -1- ((4-bromo-2-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 10.4 (s, 1), 8.0 (s, 1), 7.6 (dd, 1), 7.3 (m, 2), 5 7.0 (m, 3), 4.8 (m, 3), 4.1 (br d, 1), 3.5 (m, 3), 3-. 0 (m, 1), 2.7 (dd, 1), 2.3 (d ,.l), 1.3 (m, 3), 0.9 (m, 3) ppm; 1- ((4-chloro-2-methoxycarbonylphenoxy) methyl.) Carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; 'NMR (DMSO-d6) 0 11.0 (br d, 1), 7.7 (m, 3), 7.6 (dd, 1), 7.3 (t, 2), 7.0 (d, 1), 5.0 (do, 2), 4.7 (m, 1), 4.4 (m, 3), 3.8 (m, 4) -, 3.4 (m, 2), 3.0 (m, 2), 1.4 (d, 1.5 ; ), 1.2 (d, 1.5) ppm; (trans) -1- ((4-Chloro-2-methoxycarbonyl) enoxy) methyl) car-5-bonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; NMR (CDCl 3) 7.9 (br s-, -2), 7.8 (s, 1), 7.4 (m, 1), 7.1 (t, 2), 7.0 (d, 1 ), 4.8 (m, 3), 4.4 (m, 2), 3.9 (m, A), 3.5 (m, 2), 2.8 (m, 2), 1.6 (m, 3), 1.3 (m, 3) ppm; 0 1- ((4-chloro-2-aminocarbonylphenoxy) methyl) carbonyl-2-methyl-4- (4-f luorobenzyl) piperazine; NMR (CDCl 3) 9.6 (br s, '1), 8.0 (s, 1), 7.6 (dd, 1), 7.4 (dd, 2), 7. 2 (t, 2 ), 6.9 (d, 1), 5.0 (m, 3), 4.4 (m, 2), 4.0 (m, 1), 3.8 (m, 2), 3.6 (m, 1), 3.1 (m, 1), 2.9 (m, 1), 1.6 (d, 1.5), 1.4 (d, 1.5) ppm; l- ((4-chloro-2- (aminocarbonyl) phenylamino) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-de) 11.2 (br s, 1), 7.9 (br s, 1), 7.7 (m, 3), 7.2 (m, 2), 6, 6 (d, 1), 4.8 (br s, 1), 4.4-3.9 (m, 6), 3.4 (d, 1), 3.0 (m, 3), 1.4 (m, 3) ppm; (2R) -1- ((4-Chloro-2-aminocarbonylphenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 9.1 (s, 1), 8.2 (s, 1), 7.4 (dd, 1), 7.3"(m, 3), 7.0 (t, 2), 6.8 (d, 1), 5.8 (br s, 1), 4.8 (m, 3), 3. 5 (m, 3), 2.9 ( d, 1), 2.7 (d, 1), 2.2 (m, 2), 1.4 (d, 1.5), 1.3 (d, 1.5) ppm; 1- ((4-chloro-2-formylphenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 11.0 (br d, 1), 10.4- (s, 1), -7.6 (m, 4), 7.3 (t, 2), 7.2 (d, 1), 5.2 (m, 2), 4.7 (m, 1), 4.3- (m, '3), 3.9 (m, 1), 3.6 (m, 1), 3.1 (ra, 3), 1.5 (d, 1.5), 1.3 (d, 1.5) ppm; (2R, 55) -l - ((4-chloro-2-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 10.5 (s, 1), 7.8 (s, 1), 7.5 (d, 1), 7.3 (m, 2), 7.0 (t, 3), 4 , 8 (m, 3) ', 41 (m, 1), 3.5 (m, 3), 3.1 (br s, 1)', 2, 1 (dd, 1), 2. 3 (dd , 1), 1.3 (m, 3), 0.9 (m, 3) ppm; (2R) -1- ((4-chloro-2-formylphenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 10.4 (s, 1), 7.8 (s, 1), 7.5 (d, 1), 7.3 (m, 2), 7.0 (t, 3), 4.8 (br s, 2), 4.7 (m, 1), 4.2 (m, 1), 3.4 (m, 3), 3. 1 (m, 1), 2 , 8 (br d, 1), 2, -6 (br d, 1), 2.1 (m, 1), 2.0 (dd, 1), 1.3 (m, 3) ppm; (trans) -1- ((4-Clo.ro-2-cyanophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.5 (dd, 1), 7.3 (m, 2), 7.0 (m, A), 4.8 (m, 3), 4.1 (m, 1), 3.5 (m) , 3), 3.0 (m, 1), 2.7 (m, 1), 2.2 (m, 1), 1.3 (m, 3), 0.8 (m, 3) ppm; (trans) -1- ((4-chloro-2-acetylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d 6) - 10.8 (br d, 1), 7.8 (s, 2), 7.5 (m, 2), 7.3 (m, 3), 7. 2 (m, 1), 5.3 (m, 1), - 5.0 (s, 2), 4.3 (m, 3), 4.0 (m, 1), 3.8-3.3 (m, 2), 2. 8 (m, 1), 2.6 (s, 3), 1.4 (dd, 3), 1.3 (m, 3) ppm; 1- ((2- (acetylamino) phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 11.0 (br s, 1), 9.4 (s, 1), 8.0 (d, 1), 7.6 (d, 2), 7.3 (t, 2), • 7.0 (m, 3), 4.9 (q, 2), 4.7 (m, 1), 4. 3 (m, 3), 3.9 (m, 1), 3 , 6-2.8 (m, 4), 2.1 (s, 3), 1.4 (d, 1.5), 1.3 (d, 1.5) ppm; (trans) -1- ((3-cyanophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 11.0 (br d, 1), 7.9 (s, 2), '7.5-7.3 (m, 6), 5.2 (d, 1), 4, 9 (m, 2), 4.3 (m, 3), 3.6 (m, 2), 3.2 (m, 1), 2.8 (m, 1), 1.5-1.2 (m, 6) ppm; (2R, 5S) -1- ((3-hydroxy-5-methylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-de) 10, 5 (br d, 1), 9.3 (s, 1), 7.8 (s, 2), 7. 2 (m, 2), 6.2 (s, 2), 6.1 (s, 1), 4.7 (m, 4), 4. 3 (m, 3), 3.8 (m, 1), 3.6 (m, 1), 2.8 (m, 1), 2.2 (s, 3), 1.4 (m, 3 ), 1.2 (m, 3) ppm; (trans) -1- ((4-methyl-2-aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO- de) 11, -0 (br m, 1), 7.8 (s, 2), '7, 2 (m, 5), 5.3 (m, 1), 5. 0 ( m, 2), 4.3 (m, 3), 4.0 (m, 1), 3.5 (m, 2), 2.8 (m, 1), 2.2 (s, 3), 1.3 (m, 6) ppm; (trans) -1- ((3-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 11.0 (br d, 1), 10.0 (s, 1), 7.9 (s, 2), 7.5 (m, 2), 7.3 (m, 3), 6.9 (m, 1), 5. 2 (m, 1), 4.9 (m, 2), 4.3 (m, 3), 4.0 (m, 1), 3.6 (m, 2), 2.8 (m, 1), 1.3 (m, 6) ppm; (trans) -1- ((4-methyl-2-acetylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 7.5 (s, 1), 7.3 (m, 3), 7.0 (t, 2), 6.8 (d, 1), 4.7 '5 (m, 3 ), 4.2 (br d, 1), 3.6 (m, 1), 3.5"(q, 2), 3.0 (br s, 1), 2.7 (m, A), 2. 2 (m, 4), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((2-methoxycarbonylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 0 12.1 (s, 1), 7.8 (m, 3), 7.3 (br s, 1), 7.0 (br s, 4), 4.8 (m, 2), 4.3 (m, 3), 3, .9 (m, 5), 3.6 (m, 1), 2.8 (m, 1), 2 , 4 (m, 1), 1.6 (m, 3), 1.3 (m, 3) ppm; (trans) -1- ((3-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 10.8 5 (br d, 1), 7.8 (m, 3), 7.7 (m, 1), 7.6 (t, 1), 7.4 - (d, 1), 7.3 (t, 2), 5.2 (m, 1), 5.0 (m, 2), 4".7 (m, 1), 4.3 (m, 3), 4.0 (m, 1), 3.6 (m, 1), 2.8 (m, 1), '1.4 (m, 3), 1.3 (m, 3) ppm; (trans) -1- ((4-acetyl-2- (aminocarbonyl) phenoxy) me-0-tyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 9.7 (br d, 1), 8.6 (s, 1), 8.5 (s, 1), 8.1, (d, 1), 7.8 (s, 1), 7.6 (br s , 3), 7.3 (t, 3), 5.4 (d, 1), 5.1 (m, 2), 4.6 (m, 1), 4. 3 (s, 2), 4 , 2 (m, 1), 3.7 (m, 1), 3.4 (m, 1), 3.0 (m, 1), 2.6 (s, 3), 1.4 (m, 3), 1.2 (m, 3) ppm; (trans) -1- ((4-nitro-3-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluoro-benzyl) piperazine; NMR (DMSO-d6) 11.2 (br d, 1), 8.0 (m, 3), 7.3 (m, 2), 7.0 (m, 2), 5.3 (d, 1), 5.0 ( m, 2), 4. 3 (m, 3), 3.7-3.3 (m, 2), 3.0 (m, 1), 2.8 (m, 1), 2.6 (s) , 3), 1.4 (m, 3), 1.3 (m, 3) ppm; (trans) -1- ((5-nitro-2-methylphenoxy) methyl) carbonyl-2, 5-dimethyl-4 ~ (4-fluorobenzyl) piperazine; NMR (DMSO-de) 10.5 (br d, 1), 1.1 (m, A), 7.4 (d, 1), 7.3 (t, '2), 5. 3 (d, 1), 5.1 (m, 2), 4.7 (m, 1), 4.3 (m, 2), 3.9 (q, 1), 3.6 (br d, 1), 3 4 (m, 1), 2.9 (dd, 1), 2.3 (s, 3), 1.4 (m, 3), 1.3 (m, 3) ppm; (trans) -1- ((4-amino-3-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-de) 11.2 (br d, 1), 7.9 (t, 2), 7.3 (m, 4), 7.0 (d, 1), 4.8 (m, 3), 4.3 (m, 3), 3.9 (m, 1), 3.6 (m, 1), 3.2 (m, 1), 2.8 (t, 1), 1, 4 (dd, 3), 1,3 (dd, 3) ppm; (trans) -1- ((5-nitro-2-aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMS0-d6) 11.2 (br d, 1), 7.9 (t, 2), 7.7 (d, 1), 7.6 (s, 1), 7.3 (t, 2) ), 6.7 (d, 1), 5. O (m, 3), 4.7 (m, 1), 4.3 (m, 2), 4.0 (q, 1), 3.6 (m, 1), 3.3 (m, 1), 2.8 (t, 1), 1.4 (dd, -3), 1.3 (dd, 3) ppm; (trans) -1- ((2-aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 11.3 (m, 1), 7.9 (br s, 2), 7.8 (br m, 1), 7.3 (m, 4), 7.0 (t, 1), 5.3 (m, 1), 5.0 (m, 2), 4.6 (m, 1), 4.3 (m, 2), 3.6 (m, 3), 2, 8 (m, 1), 1.3 (m, 6) ppm; (trans) -1- ((3-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 10.5 (brd, 1), 7.8 (s, 2), 7.3 (m, 2), 7.1 (t, 1), 6.5 (m, 3), 4.8 (m, 2), 4.3 (m, 3), 3.8 (m, 1), 3.6 (m, 1), 3. 4 (m, 2), 2, 8 (t, 1), 1.4 (m, 3), 1.2 (m, 3) ppm; (trans) -1- ((4-methoxy-2-acetylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine;; NMR (DMSO-de) 11.2 (br s, 1), 7.9 (br s, 2), 7.3 (m, 3), 7.1 (s, 2), 5.2 (d, 1), '4.9 (s, 2), 4.3 (ra, 3), 3.9-3.4 (ra, 9), 2.8 (m, 1), 1.4-1.2 (m, 6) ppm; (trans) -1- ((5-methoxy-2-acetylphenoxy) -ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-de) - 11.2 (br d, 1), 7/9 (dd, 2), 7.6 (m, 1), 7.3 (t, 2), 6.6 (q, 2), 5.3 (d, 1), 5.0 (s, 2), 4.3 (m, 3), 3.8 (s, 3), 3.4 (m, 3), 2, 8 (m, 1), 2.6 (s, 3), 1.5-1.2 (m, 6) ppm; (trans) -1- ((2- ((2-hydroxyethyl) aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-de) 10.8 (br d, 1), 9.1 (br s, 1), 7.9 (d, 1), 7.8 (br s, 2), 7.4 (t , 1), 7.2 (m, 3), 7.0 (t, 1), 5.2 (d, 1), 5.0 (m, 2), 4. 3 (m, 3), 3 , 9-3, '4 (m, 7), 2.8 (dd, 1), 14-1.2 (m, 6) ppm; (trans) -1- ((2- ((2-hydroxyethoxy) carbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d e) 10.0 (br s), 7.7 (m, 3), 7.4 (t, 1), 7.3 (t, 2), 7.0 (dd, 2) , 5.0 (m, 2), 4.5 (m, 1), 4.2 (m, 5), 3.8 (q, 1), 3.6 (t, 2), - 3.4 (m, 2), 2.9 (m, 1), 1.3 (m, 3), 1.2 (m, 3) ppm; (trans) -1- ((2- (2-hydroxyethoxy) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-de) 10, .5 (br d, 1), 7.8 (t, '2, 7.3 (t, 2), 6.9 (m, 4), 4.8 (m, 3), 4.4 (m, 1), 4.3 (m, 2), 3.9 (m, 3), 3.6 (m , 3), 3.4 (m, 1), 2.8 (m, 1) -, 1.4 (m, 3), 1.2 (m, 3) ppm; (trans) -1- ((2-Acetyl-4,5-dimethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d e) 10.4 (br s, 1), 7.8 (m, 2), 7.4 (s, 1), 7. 2 (t, 2) -, 6. 8 (m, 1), 5.2 (d, 1), 4.9 (s, 2), 4. 3 (m, 3) ,. 3.8 (m, l), - 3.6 (m, 1), 3.4 (m, 1), 2.8 (m, 1), 2.6 (s, 3), 2.2 ( s, 3), 2.1 (s, 3), 1.4 (m, 3), 1, 2 (m-, 3) ppm; (trans) -1- ((5-methoxy-2- (methoxycarbonyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4 - (4-fluorobenzyl) piperazine; NMR (DMSO-de) , 0 (br d, 1), 7.9 (br s, 2), 7.7 (d, 1), 7.3 (m, - 2), 6.6 (m, 2), 5.0 (m, 3), 4.3 (m, 3), 3.8 (s, 3), 3.7 (s, 3), 3. 6 (m, 1), 3. 4 (m, 2), 2.8 (dd, 1), 1.4 (dd, 3), 1.2 (dd, 3) ppm; 1- ((4-chlorophenylamino) methyl) carbonyl-2-methyl-4- (4-fluo-robenyl) piperazine; NMR (DMSO-d6) 7.4 (t, 2), 7.15 (t, 2), 7. 1 (d, 2), 6.6 (d, 2), 5.8 (t, 1) , 4. 5 (m, -1), 4.2. (m, 1) -, - 3, 9 (m, 1), 3.7 (m, 1), 3.4 (m, 1), .3.3 (m, 1), 2.9 (m , 1), 2.8 (d, 1), -2.6 (d, 1), 2.0 (m, 2), 1.3 (d, 1.5), 1.1 (d, 1) , 5) ppm; (trans) -1- ((Benzo [b] pyran-2-on-7-yloxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.6 (d, 1), 7.4 (d, 1), 7.3 (ra, 2), 7.0 (m, 3), 6.8 (s, 1), 6, 3 (d, 1), 4.7 (m, 3), 4.1 (m, 1), 3.6 (m, 3), 3.0 (br s, 1), 2.7 (br d , 1), 2.2 (d, 1), 1.3 (m, 3), 1.0 (m, 3) ppm; (trans) -1- ((2-Chloro-4-carboxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((1-Nitroso-3,6-di (hydroxysulfonyl.) naphthalene - 5,9-yloxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-Nitroso-4-hydroxysulfoniinaphthalen-1-yloxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; 0 (trans) -1- ((3,6-di (hydroxysulfonyl) naphthalen-1-yloxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-hydroxysulfonyl-6-aminonaphthalen-1-yloxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) pi-5 perazine; (trans) -1- ((3-hydroxysulfonyl-7-aminonaphthalen-1-yloxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((5-hydroxysulfonylquinolin-8-yloxy) me-0-tyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,3-dinitro-7-hydroxysulfonylnaphthalene-1-yloxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluo-robenzyl) piperazine; (trans) -1- ((2-carboxy-4-hydroxysulfonylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; 5 (trans) -1- ((2-amino-4-hydroxysulfonylphenoxy) methyl) carbonane-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-formyl-2,6-di-t-butylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((A- (morpholin-4-yl) methyl-2, 5-dimethylphe-10-noxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((4- (methoxycarbonyl) -2,6-dichlorophenoxy) raylethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) pipe.razine; 1.5 (trans) -l- ((4- (hydroxysulfonyl) naphthalen-1-yloxy) methyl) -e-ar-bonyl-2,5-dimethyl-l- 4- (4-fluorobenzyl) piperazine; (trans) -l- ((3,6-di (hidoxysulfonyl) -8-aminonaphthalen-1-yloxy) methyl) carbonyl-2, 5-diraethyl-4- (4-fluorobenzyl) -0 piperazine; (trans) -l- ((2-carboxy-5-aminophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-trifluoromethyl-2, 3,5,6-tetrafluoro-deenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-4-formyl-5- (2-hydroxy-3-methoxy-5-formylphenyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) ) piperazine; (trans) -1- ((-4-carboxy-2, 3,5,6-tetrafluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4- (adamant-1-yl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; 10 - (trans) -l- ((2- (adamant-1-yl) -4-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2, A-di ((1-methyl-1-phenyl) ethyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) pipera-'15 zina; - - (trans) -l - ((2-acetyl-4-bromophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-nitro-4-t-butylphenoxy) methyl) carbonyl-. 2,5-dimethyl-4- (4-fluorobenzyl) piperazine; 20 (trans) -l- ((2-acetyl-4-chloro-5-methylphenoxy) methyl) carbonane-2, 5-dimethyl-4 ~ (4-fluorobenzyl) piperazine; . (trans) -1- ((2-Acetyl-4-chloro-6-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (A-fluorobenzyl) piperazine; (trans) -1- ((2-Acetyl-4,6-dibromophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) pipe.razine; (trans) -1- ((2-formyl-4,6-di (t-butyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; 5 (trans) -1- ((3,5-dinitrophenoxy) methyl) carbonyl-2,5-dimethyt-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2,6-dichloro-4-ethoxycarbonylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) -piperazine; 10 (trans) -l- ((2-ethoxycarbonyl-4-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-methoxy-6- (prop-3-enyl) phenoxy) methyl) carbonane-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3-fluoro-4-cyanophenoxy) methyl) carbonyl-2-, 5-15-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-Acetyl-4-methyl-6-nitrophenoxy) methyl) carbonane-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methylbenzothiazol-5-yloxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; 20. (trans) -1- ((2-carboxy-4- (hydroxysulfonyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) pipe-razine; (trans) -1- ((4- (4- (trifluoromethyl) phenoxy) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2- (li? -pyrazol-3-yl) -4-chloro-5-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (li? -pyrazol-3-yl) -4-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((2-phenyl-4-oxo-7-hydroxy-4i? -l-benzopyran-3-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) ) piperazine; (trans) -1- ((2-Chloro-3-trifluoromethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-4- (butoxymethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((6-hydroxyquinolin-2-yloxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxycarbonyl-6-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,5-di (t-butyl) -4-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-formyl-4-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2- (2 # -benzotriazol-2-yl) -4- (2-hydroxy-ethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) ) piperazine; (trans) -1- ((4-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (methylthio) pheno-xi) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3,5-di (t-butyl) -4-butylphenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3,5-dibromo-4-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2,6-diiodo-4-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-Nitro-4-i-methoxycarbonylphenoxy) methyl) carbo- nyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2- (ethoxycarbonyl) indol-5-yloxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3- (2-carboxyethyl) phenoxy) ethyl) carboryl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-dinitro-4- (carboxymethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-nitro-3-carboxyphenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((6-Carpoxynaphthalen-2-yloxy) methyl) carbonyl-2,5-dimethyl-4 - '(4-fluorobenzyl) iperazine; (trans) -l- ((2,6-difluoro-4-ethylcarbonylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (2- (methoxycarbonyl) ethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (prop-3-enyl) -4-acetylphenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobeakyl) piperazine; (trans) -l- (((3-Oxo-2J? -benzofuran-6-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4,6-tribromo-3,5-dimethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((A- (heptycarbonyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-4-acetylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-nitro-4-phenylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) -peperazine; (trans) -1- ((2-methoxy-4- (eth-2-enyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-Chloro-4-methoxycarbonylphenoxy) -methyl) -carbonyl-2,5-dimethyl-4 ~ (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-diiodo-4-cyanophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2,6-diiodo-4-carboxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- (((2-phenyl-4-oxo-4i? -l-benzopyran-5-yl) oxy) methyl) carbonyl-2,5-diraethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((2-phenyl-4-oxo-7-methoxy-4i? -l-benz.opyran-5-yl) oxy) -ethyl) carbonyl-2, 5-dinaethyl-4- (4 -fluorobenzyl) piperazine; • - - (trans) -1- (((2-phenyl-4-oxo-7-methoxy-2,3-dihydro-4i? -l-benzopyran-5-yl) oxy) methyl) carbonyl-2, 5 -dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((4-octylcarbonylphenoxy) methyl) carbonyl-2, 5-. dimethyl-4- (4-fluorobenzyl) -piperazine; (trans) -l- (((4-phthalimid-1-ylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3- (morpholine-4) -yl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3-chloro-4-bromophenoxy) methyl) carbonyl-2, 5-dimethyl- 4- (4-fluorobenzyl) piperazine; (trans) -l- (((2-oxo-7-methoxy-2i? -l-benzopyran-8-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4 - (4-fluorobenzyl) iperazine; (trans) -1- ((2-acetyl-5-fluorophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ( (2- (1-methylcyclohex-1-yl) -4-methyl-6- (2-hydroxy-3- (1-methylcyclohex-1-yl) -5-methylbenzyl) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-formyl-3-methoxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-amino-4-carboxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-chloro-4-) carboxy-6-methoxyphenoxy) methyl) carbonane-2, 5-dim ethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2,6-dimethyl-4-carboxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-methoxy-4- (2- (carboxy) ethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2,6-dimethoxy-4-hydroxymethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-dibromo-4-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-nitro-4- (ethoxycarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-amino-4- (methoxycarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((4- (2- (4-nitrophenyl) eth-2-enyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-Acetyl-3,5-dimethoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-di (t-butyl) -4- (methoxycarbonyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4 -. (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-4- (ethoxycarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-cyclohexyl-4-chlorophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-phenylbenzyl) piperazine; (trans) -1- ((2,6-dimethyl-4-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-4-ethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-n-butylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((3-carboxy-l-bromonaphthalen-2-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-bromo-4-nitro-6-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-formyl-4-chlorophenoxy) methyl) carbonyl-2, .5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-dichloro-4- (ethoxycarbonyl) phenoxy) -ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((4-methyl-2-oxo-2H-1-benzopyran-6-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,3-dibromo-4-formyl-6-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((4- (2- (4-nitrophenyl) eth-2-yl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4-, 6-tribromo-3-forraylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-benzyl-4-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (bezothiazol-2-yl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-nitro-6-fluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-ethoxy-4-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-bromo-4,6-di (t-butyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) - ± - ((2- (pyrrolidin-1-yl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine (trans) -1- ((2- (morpholine- 4-yl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2- (piperidin-1-yl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -l- ((2-formyl-4-chloro-6-bromophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) p-iperazine; (trans) -1- (((4,7-dimethoxy-5-formylbenzofuran-6-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; - - - (trans) -1- (((2-oxo-4-methyl-8-nitro-2ií-l-benzopi.ran-7-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (A-fluorobenzyl) .piperazine; (trans) -1- ((2-methoxy-4-bromophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-chloro-4-bromo-6-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2,4-dimethyl-6-t-butylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((2-nitro-4- (hydroxysulfonyl) naphthalen-1-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((3 -. (hydroxysulfonyl) -6-aminonaphthalen-1-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- (((3- (hydroxysulfonyl) -7-aminone-phthalen-1-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluoro-benzyl) piperazine; (trans) -1- (((3- (methoxycarbonyl) naphthalen-2-ii) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-4- (hydroxysulfonyl) phenoxy) methyl) carbonyl-2, -5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ('(4-n-Butylcarbonylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-ethoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans-I- ((4- (((2-ethyl) hexoxy) carbonyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4 - ((n-pentoxy) carbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-nitro-5- (methoxycarbonyl) phenoxy) ) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,, 6-tribromo-3-methylphenoxy) methyl) carbonyl-2,5-dimethyl 4- (4- fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-5-methylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperaziria; (trans) -1 - ('(3-methoxy-4-formylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4- (2- (phenyl) eth-2 -enyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4- (1, 2,4-triazol-1-yl) phenoxy) ) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-nitro-4-chloro-5-methylphenoxy) methyl) car- • bonyl-2 , 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((4- (n-hexoxycarbonyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-Chloro-4-formyl-6-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-4- (2- (ethoxycarbonyl) ethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,3,4,6-tetrachlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- ((2-methylpropoxy) carbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (n-butoxycarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((4- (phenylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-hydroxymethyl-4-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-mercaptophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine: (trans) -l- ((2-nitro-6-formylphenoxy) methyl) carbonyl -2,5-dimethyl-i-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4-di (1-methylbutyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-trifluoromethyl-4-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-dibrorao-4- (methoxycarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; Ctrans ^ -1- ((2,4-dichloro-6-acetyl) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxycarbonyl-4-methylphenoxy) methyl) carbonyl-2,2-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-formyl-4-bromo-6-methoxyphenoxy) methyl) carbonane-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-diformyl-4-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-dinitro-4-carboxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-nitro-4-acetylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-formyl-4-nitro-6-methoxyphenoxy) methyl) carbonane-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((4- (aminocarbonyl) methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-methoxycarbonyl-4-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- (((2-phenyl-4-oxo-4i? -l-benzopyran-6-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-chloro-4-trifluoromethylphenoxy) methyl) carbo- nyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-3-methyl-6-isopropylphenoxy) methyl) carbonyl-2,5-diraethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((5,7-dibromo-2-methylquinolin-8-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- (((5,7-dichloro-2-methylquinolin-8-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2, -6-dinitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; . { trans) -1- ((2-nitro-4-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; ('tas -! - ((2-amino-4- (1,1-dimethylpropyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (( 2,6-diphenyl-4-aminophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2,4-dichloro-3-methyl-6-aminophenoxy) ) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((2-oxo-A- (carboxy) methyl-2i? -l-benzopyran- 7- il) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((2-oxo-4-trifluoromethyl-2H-1-benzopyran-7- ilo) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-t-butyl-4-methoxyphenoxy) methyl) carbonyl- 2, 5 -dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-formyl-6-methylphenoxy) methyl) carbonyl-2,5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxycarbonyl-4-'5-acetylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-bromo-5-fluorophenoxy) methyl) carbonyl-2, 5- dimethyl-4- (4-fluor) obencil) piperazine; ftrans; -l- ((2,4-di (1,1-dimethylpropyl) phenoxy) methyl) car-0. bonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3-methyl-4-fluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f-luorobenzyl) piperazine; (trans) -l- ((2, 3, 4-trifluorophenoxy) methyl) carbonyl-2,5- dimethyl-4- (4-fluorobenzyl) piperazine; 5 (trans) -1- ((2,5-difluoro-phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; - - -. (trans) -1- ((2-methyl-5-nitrophenoxy) methyl) carbonyl-2, -5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((2-methyl-3- (ethoxycarbonyl) indol-5-0 yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-aminocarbonyl-4-acetylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-dinitro-3-t-butylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; • (trans) -l- ((2-fluoro-4-nitrophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (A-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-3-fluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2- (2-ethylhexoxy) carbonylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4,6-tribromo-4-carboxyphenoxy) methyl) carbonane-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4- (4-bromophenyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((A- (4-carboxyphenyl) phenoxy) methyl) carbonyl-2,5- dimethyl-4- (4-fluorobenzyl) piperazine; ('trans; -! - ((2, 3, 6-trifluoro-phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2,4, 5-trifluorophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4,6-trifluorophenoxy) -methi) carbonyl-2, 5-dimethyl- 4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-fluoro-5-trifluoromethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) - l- (((2,4-dinitronaphthalen-1-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((3,6) -di (hydroxysulfonyl) -8-aminonaphthalen-1-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-acetyl-4-chlorophenoxy) ) methyl) carbonyl-2, 5-diraethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-dimethyl-4- (1- (3,5-dimethyl-4-hydoxy) phenyl) -1-methylethyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((A- (3- (4-hydroxy enyl) hex-2 -yl) phenoxy) methyl) carbonyl-2, 5-d imethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((6- (hydroxysulfonyl) naphthalen-2-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-Chloro-4-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) -piperazine; (trans) -1- ((-2-bromo-4,5-difluorophenoxy) methyl) carbonyl- ' 2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-Chloro-4-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-methoxy-4-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((A- (2- (methoxycarbonyl) ethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-diphenyl-4-nitrophenoxy) methyl) carbonyl-2, -dimethyl-4- (4-fluorobenzyl) piperazine, (trans) -1- ((2-amino-3-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-methyl-4-fluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methyl-4-iodophenoxy) methyl) .carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-fluoro-6-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-3-isopropyl-6-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-3,4,6-trichlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-ca-r-boxi-6 ~ isopropylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (piperidin-1-yl) -4-methylphenyloxy) methyl) carbonyl-2,5-dimethyl-4 ~ (4-fluorobenzyl) piperazine; (trans) -1- (((2,3-dihydro-2,2-dimethylbenzofuran-7-yl) oxy) methyl) carbonyl-2,5-diraethyl-4- (4-fluprobenzyl) piperazine; (trans) -1- ((2,6-di (t-butyl) -4- (1-methylpropyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-methyl-4-bromophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((phenanthren-9-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-nitro-4-bromophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-fluoro-3- trifluoromethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-nitro-5-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-chloro-4-aminophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-flu-robenyl) piperazine; (trans) -l- (-> (2-formyl-4-bromo-6-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-methoxy-4- (acetyl) methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((A- (5-mercaptotetrazol-1-yl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2,4,6-triiodo-3 ~ (2-carboxy) butylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3-hydroxymethyl-4-nitrophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; ftrans; -l- ((2, 3, 5, 6-tetrafluoro-4- (2,3,4,5, β-penta-fluorophenyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4 - fluorobenzyl) piperazine; (trans) -l- ((2- (benzotriazol-2-yl) -4,6-di (1, 1-dimethylpropyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (-fluorobenzyl) iperazine; (trans) -1- ((2-phenyl-3-hydroxy-4-oxo-4'-l-benzopyran-6-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((indanenyl) oxy) methyl) carbonyl-2, 5-dimethyl-4- ((A-fluorobenzyl) piperazine; (trans) -l- ((2-nitro-4- (hydroxysulfonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-nitro-3-methylphenoxy) methyl) carbonyl-2,5-diraethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4- (2, 4-dinitrophenyl) aminophenoxy) methyl) carbonane-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3"-raethyl-4-nitrophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; - (trans) -1- ((2,6-dibromo) -4-nitrophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-diiodo-4-nitrophenoxy) methyl) carbonyl- 2, 5- dimethyl-4- (4-fluorobenzyl) piperazine: (trans) -l- ((2-formyl-4-nitro-phenoxy) methyl) carbonyl-2,5- dimethyl-4- (4-fluorobenzyl) piperazine; ) -1- ((2-aminophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-amino-5-nitrophenoxy) methyl) carbonyl-2 5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-amino-5-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; trans) -l- ((2-amino-4-chlorophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (rans) -1- ((2-amino-4-carboxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-amino-4-t-butylphenoxy) methyl) carbonyl-2,5-dimethyl-4- ( 4- flu orobenzyl) piperazine; (trans) -1- ((2-amino-4-methyl-phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methyl-3-araphenophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-5-aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3-methyl-4-aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; Ctrans; -1- ((2,5-dimethyl-4-aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-dibromo-4-aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans,) -1- ((2-carboxy-4-aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-aminocarbonylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-aminocarbonyl-4-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; - (trans) -1- ((4- (-2-aminoethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; - (trans) -1- ((2,4,6-tri (dimethylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-hydroxymethyl-6-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,3-dimethoxyphenoxy) -ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4- (methoxycarbonyl) -5-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-methoxy-4- (methoxycarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; ('trans; -! - ((2,6-dimethoxy-4- (prop-3-enyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl)' piperazine; (trans) - 1- ((2-Acetyl-5-methoxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-acetyl-4-methoxyphenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; trans; -l- ((2-acetyl-3-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-4-acetylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-dimethoxy-4) -acetylphenoxy) methyl) carbonyl-2, 5-dimethyl-4 -. (4-fluorobenzyl) piperazine; (trans) -i- ((2,6-di (t-butyl) phenoxy) methyl) carbonyl-2, 5 - dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2,4-di (-butyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3,5-di (t-butyl) phenoxy) butyl) carbonyl-2,5-, dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2, 6-di (isopropyl) phenoxy) methyl) carb onyl-2, 5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-methoxy-4- (ethoxycarbony) methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-Ethoxy-5-prop-2-enylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-5-prop-2-enylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2, '6-di (1-methylpropyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperaziha; (trans) -1- ((2,4-difluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-diphenylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-nitro-3-trifluoromethylphenoxy) methyl) carbo- 'nyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-Cyclopentyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((4-cyclopentylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,3-difluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-6-aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-amino-4-chloro-5-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3,4-difluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-6-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2,4-dicarboxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2,3-dimethoxy-5-formylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-bromo-4-fluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (- (- 2,6-Dichoro-4-fluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3-methyl-4-isopropylphenoxy) methyl) carbonyl-2, -dimethyl-4- (4-fluorobenzyl) piperazine; ftrans; -l- (((fluoren-2-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; - (trans) -1- ((2-diethylaminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-amino-3-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- (((2-oxo-3, 4, 8-trimethyl-2E-l-benzopyran-7-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzene) cyl) piperazine; (trans) -1- ((2-Acetyl-4-fluorophenoxy) methyl) carbonyl-2, 5'-dimethyl-4- (4-fluorobenzyl) piperazine; Ctrans; -! - ((2-fluoro-4-bromophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2- (methylcarbonyl) amino-5-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine;. (trans) -l- (((L-acetylnaphthalen-2-yl) oxy) methyl) carbonyl- "2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-methoxy-4-nitrophenoxy) methyl) carbonyl-2, 5-dimethyl-4 ~ (4-fluorobenzyl) iperazine; (trans) -l- ((3-methyl-5-isopropylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methyl-4-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((L-aminonaphthalen-2-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-aminonaphthalen-1-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methox-i-4- (i, -2-dihydroxyethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- (((3- (2-aminoethyl) indolin-5-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; ('trans; -! - (((5-chloroquinolin-8-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy -4- (2- (amino) ethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((A- (2- (amino)) ethyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-4- (2- (amino) ethyl) phenoxy) m'etilj carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4-diaminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-aminophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (-fluorobenzyl) piper-a-zine; - (trans; -! - ((2- (diethylamino) methyl-4-aminophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methyl-5- (2-aminobutyl) phenoxy) methyl) car- bonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- (. (2- (benzotriazol-2-yl) -4- (1, 1, 3, 3-tetramethylbutyl) phenoxy) ) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobe) ncil) piperazine; (trans) -1- ((2-nitro-4-bromo-6-fluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-iodophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (2-carboxyethyl) phenoxy) methyl) carbonyl-2, 5-diraethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-4-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-dibromo-3-carboxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-dichloro-3-carboxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-4-carboxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans; -l- ((2,6-dimethoxy-4-carboxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) pipefazine; (trans) -1- ((A- (2- carboxyethyl) phenoxy) methyl.) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (2-hydroxyethyl) phenoxy) methyl) carbonyl-2,5-dlmethyl -4 - '(4-fluorobenzyl) piperazine; (trans) -l- ((3- (2-hydroxyethyl) phenoxy) -ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((A- (2-hydroxyethyl) phenoxy) methyl) carbonyl-2, 5'-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-4- (2-hydroxyethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4-dibromo-6-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-fluoro-6-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4-dichloro-6-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4-diiodo-6-formylphenoxy) raethyl) carbonyl-2, -dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-6-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-ethoxy-6-formylphenoxy) methyl) carbonyl-2, 5-- ----- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-formyl-5- (diethylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-formyl-5-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-formyl-3,5-dimethoxyphenoxy) methyl) carbonyl-2, 5-dimethyl-1-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-formyl-4-bromophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-formyl-4-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((4-methoxynaphthalen-1-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-carboxy-5,6-dimethoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-nitro-4-methoxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((fluoren-9-on-1-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((4-hydroxy-l, 2,3,4-tetrahydronaphthalen-8-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,3,4,5,6-pentabromophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methyl-3, 4,5,6-tetrabromophenoxy) methyl) carbonane-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,3,4-trichlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) -peperazine; ('trans; -! - ((2-methyl-4-bromo-6-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- (( 2-chloro-4-fluorophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l '' ((2,4,6-triiodofenoxy) methyl) carbonyl-2, 5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-formyl-4-chlorophenoxy) methyl) carbonyl-2, 5- • dimethyl-4- (4-fluorobenzyl) piperazine; trans) -1- ((3-formylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; ('trans; -! - (((l-bromonaphthalen-2-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; ('trans; -! - (((1,6-dibromonaphthalen-2-yl) oxy) methyl) carbonyl-2, 5 -dimeti 1-4- (4-fluorobenzyl) piperazine; (trans) -l- (((l-nitrosonaphthalen-2-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- (((2,4-dichloronaphthalen-1-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((2-nitronaphthalen-1-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; Ctrans; -l- (((2-carboxinaphthalen-1-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; . (trans) -1- (((2-methylnaphthalen-1-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((3- (hydroxysuiphenyl) -7- (dimethylamino) naphthalene-1-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluo-robenzyl) piperazine; Ctrans; -1- (((4-methoxynaphthalen-1-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((L-formylnaphthalen-2-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((1-carboxynaphthalen-1-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- (((l-amino-4- (hydroxysulfonyl) naphthalen-2-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((A- (naphthalen-2-yl) aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- (((3-araneonaphthalen-2-yl) oxy) methyl) carbonyl- 2-, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-fluoro-4- (carboxymethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; - - (trans) -l- (( 2-chloro-4- (carboxymethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-4- (carboxymethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-hydroxymethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2- (hydroxymethyl) -4-bromophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, (trans) -l- ((2,6) -di (hydroxymethyl) -4-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; • (trans) -1- ((2-Rethoxy-4- (hydroxymethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-mercaptophenoxy) methyl) carbonyl-2,5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- (((2-carboxyindol-5-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((3-carboxyindol-5-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (t-rans) -l- (((indol-4-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- (((indol-5-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (benzoxazol-2-yl) phenoxy) methyl) carbonyl- 2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((2-methylquinolin-8-yl) oxy) methyl) carbonyl- '2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- (((5,7-dibromoquinolin-8-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((5,7-diiodoquinolin-8-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((5-nitroquinolin-8-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; Ctrans; -1- (((quinolin-5-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l - '(((-5- (hydroxysulfonyl) -7-iodoquinolin-8-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- (((2-phenyl-4-oxo-4-yl-l-benzopyran-7-yl) oxy) methyl) carbonyl-2, 5-diraethyl-4- (4-fluorobenzyl) piperazi- na ftrans; -1- ((2-carboxy-2, 5,7,8-tetramethyl-2,3-dihydro-l-benzopyran-6-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4- fluorobenzyl) piperazine; (trans) -1- (((2-Oxo-3-chloro-4-methyl-2i? -l-benzopyran-7-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) ) piperazine; ('trans; -! - (((2-oxo-3- (diethylamino) methyl) -4-methyl-2H-l- benzopyran-7-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4- fluorobenzyl) piperazine; (trans) -1- (((2-Oxo-6-methoxy-2H-1-benzopyran-7-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- (((2-oxo-2i? -l-benzopyran-7-yl) oxy) methyl) carbonane-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-4-formyl-6-bromophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-4-forrayl-6-iodophenoxy) methyl) carbonane-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine;. (trans) -l- ((2-methoxy-4-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-ethoxy-4-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-4-formylphenox) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2,4-dichloro-6-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2,4-dini-tro-6-formylphenoxy) methyl) carbonyl-2, 5-dimethyl-4 ~ (4-fluorobenzyl) piperazine; (trans) -1- ((2, -dinitro-6-carboxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4-dinitro-6-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2,5-dinitrophenoxy) methyl) carbohyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-Nitro-5-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-nitro-4-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4-dinitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; Ctrajs; -1- ((2-nitro-4-formylphenoxy) methyl) carbonyl-2, 5-diraethyl-4- (4-fluorobenzyl) piperazine; (trans) -! - ((2-nitro-4-formyl-6-methoxyphenoxy) methyl) carbonyl-2, 5-dimethyl-1-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-nitro-4-carboxyphenoxy) methyl) carbonyl-2,5-diraethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-nitro-4-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; - (trans) -l--. { (2,6-dinitro-4-methylphenoxy) methyl) carbonyl-2, -dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-nitro-4- (carboxymethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-dichlorophenoxy) methyl) carbonyl1-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-methoxy-5-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; ('trans; -! - ((4-cyanophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((A- (1-methyl-1-phenylethyl ) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3- (ethylamino) -4-methylphenoxy) methyl) carbonyl- 2, 5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((2-acetylnaphthalen-1-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; trans) -1- ((2- (carboxymethyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluoro-benzyl) piperazine; (trans) -1- ((4- (carboxymethyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((benzotriazol-1-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4 -fluorobenzyl) piperazine; (trans) -1- (((quinolin-2-yl) oxy) methyl) carbonyl-2, 5-di-ethyl-4- (4-fluo-obenzyl) piperazine; (trans) -1- ((4-formylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-dimethoxy-4-formylphenoxy) methyl) carbonyl - 2,5- dimethyl-4- (4-fluorobenzyl) piperazine;. (trans) -1- ((3, 4-dimethoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4,6-Tri- (t-butyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-dimethoxy-4- (methoxycarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3-trifluoromethoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; trans; -l- ((2-methyl-5-aminophenoxy) methyl) carbonyl-2, 5-diraethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((4- (4-cyanophenyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-nitro-4-aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-methylphenox) methyl) carbonyl-2, 5-dimethyl-4 - (4-fluorobenzyl) piperazine; (trans) -1- ((4- (methoxycarbonyl) methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((carbazol-2-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((2-oxo-l, 3-benzothiol-2-on-6-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- (((2-phenyl-4-oxo-4i? -l-benzopyran-3-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((2-Oxo-4-methyl-2i? -l-benzopyran-7-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((4-nitrophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, (trans) -1- ((3-carboxy-4-aminophenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-5-aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (-fluorobenzyl) piperazine; (trans) -1- (((2-phenyl-4-oxo-2,3-dihydro-4i? - l-benzopyran-6-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4 -fluorobenzyl) piperazine; (trans) -1- (((quinolin-6-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,3-diaminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4- (hydroxysulfonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((Fluorenon-9-on-2-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- (((5, 6, 7, 8-tetrahydronaphthalen-1-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; trans; -1- (((5, 6, 7, 8-tetrahydronaphthalen-2-yl) oxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -9- ((2,4,6-tribromophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; ('trans; -! - ((2,6-dibromo-4-cyanophenoxy) methyl) carbonyl-2, -dimethyl-4- (4-fluorobenzyl) piperazine; ('trans; -! - ((2-fluorophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (' trans; -! - ((2,3,5,6-tetrafluorophenoxy) ) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans; -! - ((2,6-difluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) ) piperazine; (trans) -1- (("2,3-dichlorophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobeyl) piperazine; (trans) -1- ((2 , 3,6-trichlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine (trans) -l- ((2-chloro-4,5-dimethylphenoxy) methyl) carbonyl- 2 , 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,5-dichlorophenoxy) methyl) carbonyl-2,5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-chloro-5-methylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (methylcarbonyl) aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-isopropoxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2- (benzyloxy) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-ethoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-phenylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2- (methoxycarbonyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (ethoxycarbonyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-acetyl-phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2- (ethylcarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (t-buty) phenoxy) 'methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-isopropylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; Ctrans; -! - ((2- (1-methylpropyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,3-dimethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2, 3, 5-trimethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,3, 6-trimethylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (-fluorobenzyl) piperazine; (trans) -1- ((2,4-dimethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4-, 6-trimethoxy) methyl) carbonyl-2,5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methyl-5-isopropylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,5-dimethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,5-dimethyl-4- (diethylamino) methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (t-butyl) -6-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-dimethoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-prop-3-enyl-6-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-prop ~ 2-enylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-ethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-n-propylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-fluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3,5-difluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-chloro-4-fluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; ('trans; -! - ((3,5-dichlorophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-iodophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3- (phenylamino) phenoxy) methyl) carbonyl-2,5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3- (diethylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-phenylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-acetylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-trifluoromethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; ftrans; -! - ((3-t-butylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3-isopropylphenoxy) methyl) carbonyl-2,5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3-methyl-4-acetylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; ('trans; -! - ((3, 4-dimethylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-butyl-5-methylphenoxy) ) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-isopropyl-5-methylphenoxy) methyl) carbonyl- -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-ethylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2, 6 dimethyl-4-bromophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-dibromo-4-fluorophenoxy) methyl) carbonyl- 2, 5 -dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-bromo-4-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methyl-4-chlorophenoxy) methyl) carbonyl-2,5- dimethyl-4- (-fluorobenzyl) piperazine; (trans) -1- ((2-isopropyl-4-chloro-5-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; ('trans; -! - ((4- (methylcarbonyl) aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-ethoxyphenoxy) methyl) ) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-propoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; trans) -1- ((4-n-butoxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-n-hexoxyphenoxy) methyl) carbonyl- 2, '5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-n-heptoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) - ± - ((4- (propoxycarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4- (ethylcarbonyl) phenoxy) methyl) ) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4- (1, 1, 3, 3-tetramethylbutyl) phenoxy) methyl) carbonyl-2, 5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans -1- ((4- (1,1-dimethylpropyl) phenoxy) methyl) carbonyl- 2, 5-dimet il-4- (4- fluorobenzyl) 'piperazine; (trans) -1- ((4- (1-methylpropyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-methoxy-4-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-Acetyl-4-methylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, (trans) -l- ((2- (t-butyl) -4-methylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3- (ethylamino) -4-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4- (methoxycarbonyl) methylphenoxy) methyl) carbonane-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-ethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((4-n-propylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; . (trans) -l- ((2-carboxy-4,6-dibromophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-4,6-dichlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-4,6-diiophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-6-methoxy-enoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-6-phenylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; - (trans) -l- ((2-carboxy-5-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) ~ l - '((2-carboxy-5-methoxy-noxy) methyl) carbonyl-2, -dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-carboxy-5-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-4-bromophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-4-fluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-4-chlorophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; _ (trans) -1- ((2-carboxy-4-iodophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-4-methoxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,3,4-trichlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl). piperazine; (trans) -l- ((2, 3, 4, 5, 6-pentachlorophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2,4,5-trichlorophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3- (methoxycarbonii) phenoxy) methyl) carbonyl- 2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; ('trans; -! - ((3- (ethoxycarbonyl) -phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-bromophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2, -6-dimethyl-4-bromophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4 -fluorobenzyl) piperazine; (trans) -1- ((3,5-dimethyl-4-bromophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (( 3-methyl-4-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-isopropyl-4-chloro-5-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-ethoxyphenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (t-butyl) -4-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-form'yl-4-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-4-prop-3-phenylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2- (1-phenylethyl) -4-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((A- (ethoxycarbonyl) methylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((4-trifluoromethoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-fluoro-4-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; ('trans; -! - ((2-fluoro-4-chlorophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- (((7- methoxynaphthalene-2 -yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-benzyloxy-4-cyanophenoxy) methyl) carbonyl- 2, 5-dimethyl- 4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-chloro-3,5-dimethoxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) - 1- ((2-bromo-3, 5-dimethoxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3,5-dimethoxy-4-bromophenoxy) ) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-dibromo-3,5-dimethoxyphenoxy) methyl) carbonyl-2, 5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((A-chlorophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (( 3-nitrophenoxy) methyl) carbonyl-2, 5-dimethyl-4 - (4-fluorobenzyl) piperazine; (trans) -1- ((2-ethyl-3-nitrophenoxy) methyl) carbonyl-2, 5- di methyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3,5-dimethoxyphenoxy) methyl) carbonyl-2,5-dimethyl il-A-. { -fluorobenzyl) piperazine; (trans) -1- ((2-Nitro-3-carboxy-6-methylphenoxy) -ethyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3-cyanophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-5-nitrophenoxy) methyl) carbonyl-2, 5-dimethyl-4 ~ (4-fluorobenzyl) piperazine; (trans) -1- ((2-nitro-5-carboxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3- (carboxymethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-methoxy-5-carboxyphenoxy) -ethyl) carbonyl-2,5-dimethyl-4- (4-fluoro-bensyl) -piperazine; (trans) -l- ((A- (dimethylamino) methylphenoxy) -ethyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((A- (2- (dimethylamino) ethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-carboxyphenoxy) ) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -l- (((naphthalen-1-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- ( 4-fluorobenzyl) piperazine; (trans) -! - (((5-aminonaphthalen-1-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3-nitro-4-aminophenoxy) methyl) carbonyl-2,5-dimethyl-4 ~ (4-fluorobenzyl) piperazine; trans-1- ((2,6-di (t-butyl) -4- methylphenoxy) -triethyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3-carboxy-4-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4 - (4-fluorobenzyl) piperazine; (trans) -1 ~ ((2-methyl-5-carboxyphenoxy) methyl) carbonyl- '2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-nitro-4-aminophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((A- (benzyloxy) phenoxy) methyl) carbonyl-2, 5- tell me til-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4- (aminocarbonii) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-flusrobenzyl) piperazine; (trans) -l- ((3,5-di (trifluoromethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4-dibromophen-oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2,6-dibromo-4-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2, -dichlorophenoxy) methyl) carbonyl-2, 5- • dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-methoxyphenoxy) methyl) carbonyl-Z, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3,5-dimethyl-4-brora-phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3,5-dicarboxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-Chloro-4-carboxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2,6-dichloro-4-carboxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((2-carboxyquinolin-4-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (traε) -l- ((2,6-dimethyl-4-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; Ttrans; -! - ((2,6-di (t-butyl) -4-carboxyphenoxy) methyl) car-. bonyl-2, 5-dimethyl-4 - (4-fluorobenzyl) piperazine; (trans) -1- ((2-amino-5-carboxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2,6-di (t-butyl) -4- (hydroxymethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- (((4-carboxyquinolin-2-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3? -nitro-4-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; Ctrans; -1 ~ ((3-ethyl-4-chloro-5-methylphenoxy) methyl) car-. bonyl ~ 2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3,5-di (methoxycarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -lX: r ((2- (morpholin-4-yl) methyl-4-carboxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-4-cyanophenoxy) methyl) carbonyl-2,5-dimethyl-4 ~ (4-fluorobenzyl) piperazine; (trans) -1- ((2-chloro-4-bromophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-trifluoromethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-Rethyl-4-acetylphenoxy) methyl) carbonyl-2, 5-dimethyl-4 ~ (4-fluorobenzyl) iperazine; (trans) -l- ((3- (dimethylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-methyl-4-acetylphenoxy) methyl) carbonyl-2, 5'-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3,5-dimethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((A-phenylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; ("trans; -1- ((4- (ethoxycarbonyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((A-acetylphenoxy) methyl-) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) - - ((4-benzylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-methoxy-4-carboxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((3-carboxynaphthalen-2-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4 ~ (4-fluorobenzyl) piperazine; (trans) -1- ((2- (hydroxymethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((quinolin-8-yl) oxy) methyl) carbonyl-2, 5'-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4- (aminocarbonyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-1-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3,5-dimethoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2- (cyclohexyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- (((quinolin-6-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2,4-dichloro-3-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,5-dimethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3-bromophenoxy) methyl) carbonyl-2, • 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3- (methylcarbonyl) aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-acetylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-trifluoromethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans; -l- ((4-bromophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-5-formylf.enoxi) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (-trans) -1- (((tropinon-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-nitro-5-fluorophenoxy) methyl) carbonyl-2, -5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-nitro-5-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3-formyl-4-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-5-nitrophenoxy) methyl) carbonyl-2, 5-dimethyl-4 ~ (4-fluorobenzyl) piperazine; (trans) -1- ((2-amino-4-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-amino-3-carboxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-nitro-4-aminophenoxy) methyl) carbonyl-2, 5-dimethyl-4 ~ (4-fluorobenzyl) piperazine; Ctrans; -1- ((2,6-dichloro-4-nitrophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-fluoro-4-nitrophenoxy) methyl) carbonyl-2, 5-dimethyl-4 ~ (4-fluorobenzyl) piperazine; (trans) -l- ((2,3-difluoro-6-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-chloro-4-nitrophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-nitro-4-cyanophexopy) methyl) carbonyl-2, 5-. dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-bromo-4-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3,4-dichlorophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3,5-dichlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3,4,5-trimethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-fluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3,5-dimethyl-4-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans; -l- ((4-methoxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((4- (methoxycarbonyl) phenoxy) methyl) carbonyl- 2, -dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-trifluoromethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1 ~ ((4-t-butylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((4-isopropylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) pip-erazine; (trans) -1- (((naphthalen-2-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((6-bromonaphthalen-2-yl) oxy) methyl) carbonyl-2,5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3- (hydroxymethyl) phenoxy) -ethyl) carbonyl-2,5-dimethyl-4 ~ (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-5- (hydroxymethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- (((1,3-benzodioxolan-5-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans; -! - ((2,6-dimethyl-4-nitrophenoxy) methyl) carbonyl-2, 5-diraethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-nitrophenoxy) methyl) ) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-4- (amino) methylphenoxy) methyl) carbonyl-2, 5-dimethyl-4 - (4-fluorobenzyl) piperazine; - (trans) -l- ((3- (aminocarbonyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-ffluorobenzyl) piperazine; (trans) -l- ( (3- (methoxycarbonyl) methylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (4-phenylcarbonyl) -4-fluorophenoxy) methyl ) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (1-methyl) cyclohexyl-2,4-dimethylphenoxy) methyl) carbonyl-2, 5 -dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2 ~ (benzyloxycarbanyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (4- (methyl) feriylcarbonyl) -5-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-phenylcarbonyl-5-octoxyphenoxy) methyl) carbonane-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-octylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2- (2- (carboxy) phenylcarbonyl-5- di (n-butyl) aminophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluoro-robenzyl) piperazine; (trans) -l- ((2-phenylcarbonyl-5-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (δ) -! - ((2-methoxy-4- (3-hydroxyprop-2-enyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- (((3- (phenylaminocarbonyl) naphthalen-2-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((6- (phenylcarbonyl ) naphthalen-2-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2- ((2-phenylethyl) carbonyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4 - (4-fluorobenzyl) pipérazine; (trans) -1- ((4- ((4-fluorophenyl) carbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2- (phenylamino) carbonylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-phenylcarbonylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-phenylcarbonyl-4-chloro-5-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4- (4-chlorophenyl) carbonylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-benzylcarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((2-phenylcarbonyl-4-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((A- (2-methylcarbonylethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((4-phenylcarbonylphenoxy) methyl) carbonyl-2,5- dimethyl-7- (4-fiuorobenzyl) piperazine; and (trans) -1- ((3-phenylcarbonylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine. C. similarly, the following compounds of formula (Ib) were prepared: 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-4- (benzyl) piperazine; NMR (CDCl 3) 7.6 (m, 3), 7.5 (m, A), 6.2 (s, 2), 4.6 (m, 4), 4.2 (m, 4), 3.8 (m, 9), 3.4 (m, 1), 2.6 (m, 1) ppm; -5 L - ((3-methoxyphenoxy) methyl) carbonyl-4- (benzyl) piperazine; NMR (CDC13) 7.3 (m, 5), 6.5 (m, A), 4.6 (s, 2), 3.8-3.5 (m, 9), 2. 4 (m, 4) ppm; 1- ((3,4-dimethoxyphenoxy) methyl) carbonyl-4- (benzyl) piperazine; NMR (CDCl 3) 7.8 (m, 2), 7.4 (m, 3), 6.8 (d, 0 1), 6.6 (d, 1), 6.4 (dd, 1), 4.8 (d, 2), -4.3 (m, 3), '4.0 (m, 1), 3.7 (s, 3), 3.65 (s, 3), 3.6-3.3 (m, - 8), 3.2-2 , 9 (m, 3) ppm; 1- ((phenoxy) methyl) carbonyl-4- (benzyl) piperazine and 1- (chloro) acetyl-4- (benzyl) piperazine; NMR (CDCl 3) 5 7.3 (m, 7), 7.0 (m, 3), 4.7 (s, 2), 3.6 (m, 6), 2.4- (m, 4) ppm; 1- ((4-chlorophenoxy) methyl) carbonyl-4- (benzyl) piperazine and 1- (chloro) acetyl-4- (benzyl) piperazine; NMR (CDCl 3) 7.3 (m, 7), 6.9 (m, 2), 4.6 (s, 2), 3.6 (m, 6), 2.4 (m, 4) ppm; 1- ((3-cyanophenoxy) methyl) carbonyl-4- (benzyl) piperazine; NMR (CDCl 3) 7.3 (m, 2), 7.0 (m, 4), 6.8 (m, 3), 4.4 (q, 2), 4.2 (d, -l), 3.9 (d, 2), 3.6 (ra, 3), 3.0 (m, 3), 2.6 (m, 2) ppm; 1- ((4-cyanophenoxy) methyl) carbonyl-4- (benzyl) piperazine; NMR (CDC13) 7.6 (m, 4), 7.4 (m, 3), 7.0 (d, 2), 4.9 (q, 2), "4.6 (d, 1), 4.3 (d, 2), '4.0 (d, 2), 3.6 5 (t, 1), 3. 4 (d, 2), 3.0 (m, 2) ppm; ((3- (1-methylimidazolin-2-yl) phenoxy) methyl) carbonyl-4- (benzyl) piperazine; NMR (CDCl 3) 7.5 (m, 6), 7.2 (m, 3), 5.0 (d, 2), 4.0 (m, 4), 3.3 (q, 4), 3.0 (m, 6) ppm; 10 1- ((4-chloro-2-aminocarbonylphenoxy) methyl) carbonyl -4- (4- chlorobenzyl) piperazine; NMR (DMSO-d6) 8.7 (s, 1), 1.8 (s,!), 7.7 (s, 1), 7.6 (dd, 1), 7.4 (q, 3), 7.2 (d, 1), 5.0 (s, 2), 3. 4 (br d, 4), 3.3 (s, 2), 2.4 (br d, 4) ppm; 1- ((5-chloroquinolin- '8-yloxy) methyl) carbonyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d 6) 9. 0 (s, 1), 8.5 (d, 1), 7.75 (dd, 1), 7.65 (d, 1), 7.4 (q, 2), 7.1 (d, 1), 5.1 ( s, 2), 3.5 (m, 6), 2.4 (br d, 4) ppm; '20 1- (. (3-trifluoromethoxyphenoxy) methyl) carbonyl-4- (benzyl) piperazine; 3- (3, 4, 5-trimethoxyphenoxy) propyl) carbonyl-4- (benzyl) piperazine; 1- (1- (3, 4, 5-trimethoxyphenoxy) propyl) carbonyl-4- (benzyl) piperazine; 1- (1- (3, 4, 5-trimethoxyphenoxy) pentyl) carbonyl-4- (benzyl) piperazine; 1- ((4-methoxyphenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((3,5-dimethoxyphenoxy) methyl) carbonyl-4- (benzyl) piperazine; . 1- ((3-chlorophenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- (1- (3,4,5-trimethoxyphenoxy) ethyl) carbonyl-4- (benzyl) piperazine; 1- ((3,4-dichlorophenoxy) methyl) carbonyl-4- (benzyl) piperazine '; 1- ((3,5-dichlorophenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((3, 4, 5-trimethylphenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((4-nitrophenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- (1- (3, 4, 5-trimethoxyphenoxy) septyl) carbonyl-4- (benzyl) piperazine; . 1- (1- (3, 4, 5-trimethoxyphenoxy) -2-methylpropyl) carbonyl-4- (benzyl) piperazine; 1- (1- (3, 4, 5-trimethoxyphenoxy) butyl) carbonyl-4- (benzyl) piperazine;1- ((4-bromophenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((4-fluorophenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((4-trifluoromethylphenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- (((4-chlorophenyl) thio) methyl) carbonyl-4- (benzyl) piperazine; 1- ((2-chlorophenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((4- (benzyloxy) phenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((4- (methoxycarbonyl) phenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((4- (amino) phenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((4-hydroxyphenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((4- (1-methylethyl) phenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((4- (2, 2-dimethylethyl) phenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((4- (acetyl) phenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((naphthalenyl-2-oxy) methyl) carbonyl-4- (benzyl) iperazine; 1- ((4-chloro-3,5-dimethylphenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((1,3-benzodioxolyl-5-oxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((2,4-, 6-trichlorophenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((2,3,4,5,6-pentafluorophenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((2- (benzyloxy) -4-cyanophenoxy) methyl) carbonyl-4- (benzyl) piperazine; - 1- ((2-chloro-4-bromophenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((3-bromophenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((3,5-trifluoromethylphenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- (((5-oxo-6,7,8-trihydronaphthalen-1-yl) oxy) methyl) carbonyl-4- (benzyl) piperazine; 1- (((2-oxo-2H-l-benzopyran-4-yl) oxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((2-cyanophenoxy) -ethyl) carbonyl-4- (benzyl) piperazine; 1- ((4-methyl-3,5-dibromophenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((quinolinyl-6-oxy) methyl) carbonyl-4- (benzyl) piperazine; 1- (((diphenyl) 'methoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((3- (morpholin-4-yl) phenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((2-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, hydrochloride salt; 1- ((pyridinyl-3-o'xy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((2- (benzyl) phenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((4- (benzyl) phenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((4- (formyl) phenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((2- (prop-3-enyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dibromophenoxy) ra'ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((benzothiazolyl-2-oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-cyclohexylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (benzyloxy) carbonylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((5-chloroquinolinyl-8-oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 5 1- ((4- (imidazol-1-yl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; . 1- ((3-chloro-5-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-carboxyphenoxy) methyl) carbonyl-4,10 '"(benzyl) piperazine; 1- ((4-iodophenoxy) methyl) carbonyl-4 ~ (4-chlorobenzyl) piperazine, hydrochloride salt; DMSO-de) 7.6 (m, 6), 6.8 (d, 2), 4.9 (d, 2), 4.4 (m, 3), 4.0 (m, 1), 3 , 6 (m, 1), 3.4-2.9 (m, 6) ppm; 1- ((2-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) pi- perazine; ((2,6-dimethoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methylquinolinyl-4-oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; ((2,3-dihydro-lH-inden-5-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((coumarin-4-yloxy) methyl) carbonyl-4- (4- chlorobenzyl) piperazine; 1- ((4-chlorobenzyloxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((4-chlorophenyl) amino) methyl) carbonyl-4- (4-chlorobenzyl) ) piperazine, hydrochloride salt; -RMN (DMSO-d6) 11.4 (br s, 1), 7.6 (dd, 4), 7.1 (d, 2), 6.6 (d, 2), 4.4 (m, 4), 4.0 ( m, 4); 3. 6-2.9 (m, 4) ppm; 1- ((4-chloronaphthalenyl-1-oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((4-chlorophenyl) (methyl) amino) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((di (4-chloro) phenyl) methoxy) methyl) carbonyl-4- (chlorobenzyl) piperazine; 1- ((3,5-dimethoxy-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; NMR (CDC13) 7.2 (q, 4), 6.2 (s, "-2"), 4.7 (s, 2), 3.9 (s, 6), 3.6 (m, 4), 3.5 (s, 2), 2.4 (m, 4) ppm; 1- ((5,7-dichloroquinolinyl-8-oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((6-hydroxycoumarin-4-yloxy) methyl) carbonyl-4 ~ ( 4- chlorobenzyl) piperazine; 1- ((2-formylphenoxy) -methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-fluoro-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, hydrochloride salt; NMR (DMSO-d6) 11.8 (s, 1), -7.5"(m, 5), 7.1 (d, 1), 6.8 (d, 1), 5.0 (q, 2), 4.3 (m, 3), 3.9 (m, 1), 3.6-2.9 -5 (m, 6) ppm; 1- ((2- (hydroxymethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2, -dibromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 0 1- ((2, -dichlorophenoxy) methyl) carbonyl -4- (4-chlorobenzyl) -piperazine; 1- ((4-chloro-3-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; NMR (DMSO-de) 7.6 (m, 6) , 7. 3 (d, 1), 5.0 (q, 2), 4.3 (m, 3), 3.9 (m, 1), 3.5-2.9 (m, 5 .6 ) ppm; 1- ((4-bromo-2-formylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; NMR (DMSO-d6) 11.4 (br s, 1), 7.8 (m, 2), 7.5 (m, 4), 7.2 (d, 1), 5.2 (q, 2), 4.4 (m, 3), 4.0 (m, 1), 3, 6-2.9 (m, 6) ppm; 1- ((2-methoxy-5-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-methylphenoxy) methyl) carbonyl-4 - (4- chlorobenzyl) piperazine; 1- ((4-bromo-2-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, hydrochloride salt; 1- ((2-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine hydrochloride salt; -5 1- ((3,5-dimethoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, hydrochloride salt; 1- ((2-aminocarbonyl-4-chlorophenoxy) methyl) carbonyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 8.7 (br s, 1), 7.8 (s, 1), 7.7 (s, 1), 7.6 (dd, 1)., 7.2 (m, 0 3), 7.2 (d, 1), 5.0 (s, 2), 3.5 (m, 6), 2.4 (ra, 4) ppm; 1- ((3,5-dimethoxy-4-bromophenoxy) methyl) carbonyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 4), 6.2 (s, 2), .4, 7 (s, 2), 3.9 (s, 6), 3.6 (m, 4), 3.5 (s, 2), 2.4 (m, 4) ppm; 1- ((3-formyl-4-nitrophenoxy) methyl) carbonyl-4- (4-fluoro-benzyl) piperazine; NMR (CDC13) 10.5 (s, 1), 8.2 (d, 1), 7.3 (m, 6), 4.9 (s, 2), 3.6 (m, 2), - 3.5 (m, 4), 2.4 (m, 4) ppm; 1- ((2-chloro-4-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((L-Nitroso-3,6-di (hydroxysulfonyl) naphthalen-2-yloxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-Nitroso-4-hydroxysulfonylnaphthalen-1-yloxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3,6-di (hydroxysulfonyl) -phthalen-1-yloxy) methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-hydroxysulfonyl-6-aminonaphthalen-1-yloxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-hydroxysulfonyl-7-aminonaphthalen-1-yloxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((5-hydroxysulfonylquinolin-8-yloxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,3-dinitro-7-hydroxysulfonylnaphthalene-1-yloxy) methyl) carbonyl- 4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-4-hydroxysulphonylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-amino-4-hydroxysulfonylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-formyl-2,6-di-t-butylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (morpholin-4-yl) methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((α- (methoxycarbonyl) -2,6-dichlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((4- (hydroxysulfonyl) naphthalen-1-yloxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3,6-di (hidoxysulfonyl) -8-aminonaphthalen-1-yloxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-5-aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-trifluoromethyl-2, 3, 5, 6, -tetrafluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4-formyl-5- (2-hydroxy-3-methoxy-5-formylphenyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-carboxy-2, 3, 5, 6-tetrafluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (adamant-1-yl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (adamant-l-yl) -4 ~ methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4-di ((1-methyl-1-phenyl) ethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-acetyl-4-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2-nitro-4-t-butylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2-acetyl-4-chloro-5-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-acetyl-4-chloro-6-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-acetyl-4,6-dibromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-formyl-4, β-di (t-butyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3,5-dinitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dichloro-4-ethoxycarbonylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-ethoxycarbonyl-4-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-6- (prop-3-enyl) phenoxy) methyl) carbonyl-4 ~ (4-chlorobenzyl) piperazine; 1- ((3-fluoro-4-cyanophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - ((2-acetyl-4-methyl-6-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methylbenzothiazol-5-yloxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-4- (hydroxysulfonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (4- (trifluoromethyl) phenoxy) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (L-pyrazol-3-yl) -4-chloro-5-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - 1- ((2- (li? -pyrazol-3-yl) -4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-phenyl-4-oxo-7-hydroxy-4i? -l-benzopyran-3-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-chloro-3-trifluoromethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4- (butoxymethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((6-hydroxyquinolin-2-yloxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxycarbonyl-6-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,5-di (t-butyl) -4-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2-formyl-4-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (2H-benzotriazol-2-yl) -A- (2-hydroxyethyl) phenoxy) methyl) carbonyl-4- (A-chlorobenzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2- (methylthio) phenoxy) ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3,5-di (t-butyl) -4-formylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3,5-dibromo-4-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-diiodo-4-formylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-4-methoxycarbonylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (ethoxycarbonyl) indol-5-yloxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3- (2-carboxyethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dinitro-4- (carboxymethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-3-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((6-carboxynaphthalen-2-yloxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-difluoro-4-ethylcarbonylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (2- (methoxycarbonyl) ethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (prop-3-enyl) -4-acetylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; .1 - (((3-oxo-2H-benzofuran-6-yl) oxy) methyl). carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4,6-tribromo-3,5-dimethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (heptylcarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-4-acetylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-4-phenylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4- (eth-2-enyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-chloro-4-methoxycarbonylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2,6-diiodo-4-cyanophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2,6-diiodo-4-carboxyphenoxy) methyl) carbonyl-4- (A ~ chlorobenzyl) piperazine; - (((2-phenyl-4-oxo-4H-l-benzopyran-5-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-phenyl-4-oxo-7-methoxy-4H-1-benzopyran-5-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-phenyl-4-oxo-7-methoxy-2,3-dihydro-4-l-l-benzopyran-5-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-octylcarbonylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((4-phthalimid-1-ylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3- (morpholin-4-yl) phenoxy) methyl) carbonyl-4- (4- chlorobenzyl) piperazine; 1- ((3-chloro-4-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-oxo-7-methoxy-2H-1-benzopyran-8- il) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-acetyl-5-fluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (1 -methylcyclohex-l-yl) -4-methyl-6- (2-hydroxy-3- (1-methylcyclohex-1-yl) -5-methylbenzyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2-formyl-3-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-amino-4-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-chloro-4-carboxy-6-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dimethyl-4-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4- (2- (carboxy) ethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dimethoxy-4- (hydroxymethyl) phenoxy) ethyl). carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dibromo-4-formylphenoxy) methyl) carbonyl-4- (- chlorobenzyl) piperazine; 1- ((2-nitro-4- (ethoxycarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-amino-4- (methoxycarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (2- (4-nitrophenyl) et-2-phenyl) phenoxy) methyl) carbbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-acetyl-3,5-dimethoxyphenoxy) -ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2,6-di (t-butyl) -4- (methoxycarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2-methoxy-4- (ethoxycarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) riiperazine; 1- ((2-cyclohexy-1-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dimethyl-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4-ethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-n-butylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((3-carboxy-l-bromonaphthalen-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-bromo-4-nitro-6-formylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-formyl-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dichloro-4- (ethoxycarbonyl) phenoxy) methyl) carbonyl-4- (-chlorobenzyl) piperazine; 1- (((4-methyl-2-oxo-2-l-benzopyran-6-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,3-dibromo-4-formyl-6-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (2- (4-nitrophenyl) eth-2-yl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; .1 - ((2,4-, 6-tribromo-3-formylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-benzyl-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (bezothiazol-2-yl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; i- ((2-nitro-6-fluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-ethoxy-4-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-bromo-4,6-di (t-butyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (pyrrolidin-1-yl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (morpholin-4-yl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; -1- ((2- (piperidin-1-yl) phenoxy) methyl) carbonyl-4- (-4- - chlorobenzyl) piperazine; l - ((2-formyl-4-chloro-6-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((4,7-dimethoxy-5-formylbenzofuran-6-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-oxo-4-methyl-8-nitro-2Ji-l-benzopyran-7-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-chloro-4-bromo-6-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4-dimethyl-6-t-butylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-nitro-4- (hydroxysulfonyl) naphthalen-1-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((3- (hydroxysulfonyl) -d-aminonaphthalen-1-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((3- (hydroxysulfonyl) -7-aminonaphthalen-1-yl) oxy) ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((3- (methoxycarbonyl) naphthalen-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - - 1- ((2-carboxy-4- (hydroxysulfonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-n-butylcarbonylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; - 1- ((3-ethoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (((2-ethyl) hexoxy) carbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- ((n-pentoxy) carbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-5- (methoxycarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; l- ((2,4-, 6-tribromo-3-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-5-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-methoxy-4-formylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ("(4- (2- (phenyl) eth-2-enyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (1, 2,4-triazole-1) -yl) pheno-xi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (. (2-nitro-4-chloro-5-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (n-hexoxycarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-chloro-4-formyl-6-methoxyphenoxy) methyl) carbonyl-4- (4 - chlorobenzyl) piperazine; - ((2-methoxy-4- (2- (ethoxycarbonyl) ethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2, 3, 4, 6 tetrachlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- ((2-methylpropoxy) carbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (n-butoxycarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (phenylamino) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-hydroxymethyl-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-mercaptophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 2-nitro-6-formylphenoxy) methyl) carbonyl-4 '-' (4-chlorobenzyl) piperazine; 1- ((2,4-di (1-methylbutyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - - ((3-trifluoromethyl-4-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2,6-dibromo-4- (methoxycarbonyl) phenoxy) methyl) carbonyl-4- ( 4- chlorobenzyl) piperazine; - ((2, -dichloro-6-acetyl) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2-methoxycarbonyl-4-methylphenoxy) methyl) carbonyl-4- (4 - chlorobenzyl) piperazine; 1- ((2-formyl-4-bromo-6-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-diformyl-4-methylphenoxy) methyl) carbonyl-4- (4- chlorobenzyl) piperazin a; 1- ((2,6-dinitro-4-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-4-acetylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-formyl-4-nitro-6-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (aminocarbonyl) methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxycarbonyl-4-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-phenyl-4-oxo-4-yl-l-benzopyran-6-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-Chloro-4-trifluoromethylphenoxy) methyl) carbonyl-4- (4-clprobenzyl) piperazine; 1- ((2-carboxy-3-methyl-6-isopropyl-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((5,7-dibromo-2-methylquinolin-8-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((5,7-dichloro-2-methylquinolin-8-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dinitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-4-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-amino-4- (1,1-dimethylpropyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-Biphenyl-4-aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4-dichloro-3-phenyl-6-aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- (((2-oxo-4- (carboxy) methyl-2'-l-benzopyran-7-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-oxo-4-trifluoromethyl-2H-l-benzopyran-7-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-t-butyl-4-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-formyl-6-methylphenoxy) methyl) carbonyl-4 ~ (4-chlorobenzyl) piperazine; 1- ((2-methoxycarbonyl-4-acetylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-bromo-5-fluorofinoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4-di (1,1-dimethylpropyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-Rethyl-4-fluorofinoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,3,4-trifluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,5-difluorophenoxy) -ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methyl-5-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-methyl-3- (ethoxycarbonyl) indol-5-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-aminocarbonyl-4-acetylphenoxy) -ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dinitro-3-t-butylphenoxy) -ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-fluoro-4-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2-carboxy-3-fluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2- (2-ethylhexoxy) carbonylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4,6-tribromo-4-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (4-bromophenyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (4-carboxyphenyl) phenoxy) methyl) carbanyl-4- (4-chlorobenzyl) piperazine; 1- ((2,3, 6-trifluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ('(2, 4, 5-trifluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4,6-trifluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-fluoro-5-trifluoromethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) perazine; 1- (((2,4-dinitronaphthalen-1-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((3,6-di (hydroxysulfonyl) -8-aminonaphthalen-1-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-acetyl-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dimethyl-4- (1- (3,5-dimethyl-4-hidoxyphenyl) -1-methylethyl) phenoxy) -ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; l- ((4- (3- (4-hydroxyphenyl) hex-2-yl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((6- (hydroxysulfonyl) naphthalen-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-chloro-4-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-bromo-4,5-difluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-chloro-4-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (2- (methoxycarbohyl) ethyl) phenoxy) ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-diphenyl-4-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-amino-3-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2-methyl-4-fluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine - ((2-methyl-4-iodophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-fluoro-6-methoxyphenoxy) methyl) carbonyl-4- (4'-chlorobenzyl) piperazine; 1- ((2-carboxy-3-isopropyl-6-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-3,4,6-trichlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-6-isopropylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (piperidin-1-yl) -4-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2, 3-dihydro-2, 2-dimethylbenzofuran-7-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-di (t-butyl) -4- (1-methylpropyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-methyl-4-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((phenanthren-9-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-4-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-fluoro-3-trifluoromethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-5-raetoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-chloro-4-aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-formyl-4-bromo-6-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4- (acetyl) methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; l - ((4- (5- mercaptotetrazol-1-yl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,, 6-triiodo-3- (2-carboxy) butylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-hydroxymethyl-4-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2, 3, 5, 6-tetrafluoro-4- (2, 3,4,5, 6-pentafluorophenyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (benzotriazol-2-yl) -A, 6-di (1,1-dimethylpropyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-phenyl-3-hydroxy-4-oxo-4 E-l-benzopyran-6-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((indanonyl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2-nitro-4- (hydroxysulfonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-3-methylphenoxy) methyl) carbonyl-4- (4-, chlorobenzyl) piperazine; 1- ((4- (2, 4-dinitrophenyl) aminophenoxy) methyl) carbonyl-4-. (4-chlorobenzyl) .piperazine; 1- ((3-methyl-4-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dibromo-4-nitrophenoxy) -ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-diiodo-4-nitrophenoxy) -ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-formyl-4-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-aminofinoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-amino-5-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-amino-5-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-amino-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-amino-4-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; l- ((2-amino-4-t-butylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-amino-4-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methyl-3-aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-5-aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-methyl-4-aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,5-dimethyl-4-aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dibromo-4-aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2-carboxy-4-aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-aminocarbonylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-aminocarbonyl-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((4- (2-aminoethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - (. (2,4-, 6-tri (dimethylamino) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-hydroxymethyl-6-methoxyphenoxy) -ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,3-dimethoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (methoxycarbonyl) -5-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4- (methoxycarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2, -6-dimethoxy-4- (prop-3-enyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-acetyl-5-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-acetyl-4-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2-acetyl-3-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2-methoxy-4-acetylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2,6-dimethoxy-4-acetylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2,6-di (t-butyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - 1- (('2,4-di (t-butyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; l- ((3,5-di (t-butyl) phenoxy) methyl) carbonyl- - (4-chlorobenzyl) piperazine; 1- ((2,6-di (isopropyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4- (ethoxycarbony) methylphenoxy) methyl) carbbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-ethoxy-5-prop-2-enylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-5-prop-2-enylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-di (1-methylpropyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4-difluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2,6-diphenylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-3-trifluoromethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2-cyclopentyphenoxy) -Rethyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((4-cyclopentylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,3-difluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-6-aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-amino-4-chloro-5-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenz) piperazine; 1- ((3,4-difluprophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-6-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4-dicarboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,3-dimethoxy-5-formylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-bromo-4-fluorophenoxy) methyl) carbonyl-4 ~ (4-chlorobenzyl) piperazine; 1- ((2,6-dichoro-4-fluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-methyl-4-isopropylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((fluoren-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-diethylaminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-amino-3-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-oxo-3, 4, 8-trimethyl-2i? -l-benzopyran-7-yl) oxy) methyl) carbo? Il-4- (4-chlorobenzyl) piperazine; 1- ((2-acetyl-4-fluorophenoxy) methyl) .carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-fluoro-4-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (methylcarbonyl) amino-5-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((L-Acetylnaphthalen-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, -1- ((3-methyl-5-isopropylphenoxy) -ethyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methyl-4-formylphenoxy) -ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; - (((L-aminonaphthalen-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((4-aminonaphthalen-1-yl) oxy) methyl) carbonyl-4- (4-chlorobeakyl) piperazine; 1- ((2-Raetoxy-4- (1,2-dihydroxyethyl) phenoxy) -ethyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((3- (2-aminoethyl) indalin-5-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((5-chloroquinolin-8-yl) o'xy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; . 1- ((2-methoxy-4- (2 -. (Amino) ethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (2- (amino) ethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4- (2- (amino) ethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4-diaminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-aminophenoxy) methyl) carbonyl- (4-chlorobenzyl) piperazine; 1- ((2- (diethylamino) methyl-4-aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; l - ((2-methyl-5- (2-aminobutyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (benzotriazol-2-yl) -4- (1,1,3,3-tetramethylbutyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-4-bromo-6-fluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-iodophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (2-carboxyethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-4-methylphenoxy) methyl) carbonyl-4 ~ (4-chlorobenzyl) piperazine; - 1- ((2,6-dibromo-3-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dichloro-3-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dimethoxy-4-carboxyphenoxymethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (2-carboxyethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (2-hydroxyethyl) phenoxy) methyl) ca'rbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3- (2-hydroxyethyl) phenoxy) methyl) carbonyl-4- (4 - chlorobenzyl) piperazine; 1- ((4- (2-hydroxyethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4- (2-hydroxyethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4-dibromo-6-formylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-fluoro-6-formylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4-dichloro-6-formylphenoxy) methyl) carbpnil-4- (4-chlorobenzyl) piperazine; 1- ((2,4-diiodo-6-formylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2-methoxy-6-formylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-ethoxy-6-formylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-formyl-5- (diethylamino) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1-: ((2-formyl-5-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2-formyl-3, 5-dimethoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2-formyl-4-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-formyl-4-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((4-methoxynaphthalen-1-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-5,6-dimethoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-nitro-4-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((fluoren-9-on-l-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((4-hydroxy-1,2,3-tetrahydronaphthalen-8-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2, 3, 4, 5, 6-pentabromophenoxy) methyl) carbonyl ~ 4- (4-chlorobenzyl) piperazine; 1- ((2-methyl-3, 4,5,6-tetrabromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2, 3, 4-trichlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methyl-4-bromo-6-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-chloro-4-fluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; • 1- ((2,4,6-triiodhophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-formyl-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - 1- ((3-formylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((1-bromonaphthalen-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((1, 6-dibromonaphthalen-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((1-nitrosonaphthalen-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2,4-dichloronaphthalen-1-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-nitronaphthalen-1-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-carboxynaphthalen-1-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-methylnaphthalen-1-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((3- (hydroxysulfonyl) -7- (dimethylamino) naphthalen-1-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((4-methoxynaphthalene-1-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- (((1-formylnaphthalen-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((1-carboxynaphthalen-1-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - (((L-amino-4- (hydroxysulfonyl) naphthalen-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (naphthalen-2-yl) aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((3-aminonaphthalen-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-fluoro-4- (carboxymethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-chloro-4- (carboxymethyl) phenoxy). Methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4- (carboxymethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-hydroxymethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (hydroxymethyl) -4-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6,6-di (hydroxymethyl) -4-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) 'piperazine; 1- ((2-methoxy-4- (hydroxymethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-mercaptophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 5 1- (((2-carboxyindol-5-yl) o.xi) methyl) carbonyl-4- (4-chlorobenzyl) -perazine; 1- (((3-carboxyindol-5-ii) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((indol-4-yl) oxy) methyl) carbonyl-4- (4-10 chlorobenzyl) piperazine; 1- (((indol-5-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (benzoxazol-2-yl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1.5 1- (((2-methylquinolin-8-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((5,7-dibromoquinolin-8-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((5,7-diiodoquinolin-8-yl) oxy) methyl) arbonyl-4- (4-chlorobenzyl) piperazine; 1- (((5-nitroquinolin-8-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((.quinolin-5-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - (- ((5- (hydroxysulfonyl) -7-iodoquinolin-8-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - (((2-phenyl-4-oxo-4H-l-benzopyran-7-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2-carboxy-2, 5,7,8-tetramethyl-2,3-dihydro-l-benzopyran-6-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine '; - (((2-oxo-3-chloro-4-methyl-2i? -l-benzopyran-7-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - (((2-oxo-3- (diethylamino) methyl) -4-methyl-2i? -l-benzopyran-7-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - (((2-oxo-6-methoxy-2i? -l-benzopyran-7-yl) oxy) methyl) carb? Nyl-4- (4-chlorobenzyl) piperazine; - (((2-oxo-2ií-l-benzopiran-7-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2-methoxy-4-formyl-6-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2-methoxy-4-formyl-6-iodophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2-methoxy-4-formylphenoxy) methyl) carbonyl-4- (- chlorobenzyl) piperazine; 1- ((2-Ethoxy-4-formylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2-carboxy-4-formylphenox) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4-dichloro-6-nitrophenoxy) methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4-dinitro-6-formylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4-dinitro-6-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine: 1- ((2,4-dinitro-6-methylphenoxy) methyl) carbonyl-4- (4- chlorobenzyl) piperazine; 1- ((2,5-dinitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-5-phenyl-phexy) -methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4-dinitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2-nitro-4-formylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2-nitro-4-formyl-6-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-4-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-4-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dinitro-4-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-4- (carboxymethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dichlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-methoxy-5-chlorophenoxy) methyl) carbonyl-4- (4-chloroberyl) piperazine; 1- ((4-cyanophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (1-methyl-1-phenylethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3- (ethylamino) -4-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; l - (((2-acetylnaphthalen-1-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (carboxymethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (carboxymethyl) phenoxy) methy) carbonyl-4- (4-chlorobenzyl) piperazine; - 1- (((benzotriazol-1-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; '5- 1- (((quinolin-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; .1 - ((4-formylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dimethoxy-4-formylphenoxy) methyl.) Carbonyl-4- (4-10 chlorobenzyl) piperazine; 1- ((3,4-dimethoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; ' 1- ((2, 4, 6-tri (t-butyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; d 1- ((2,6-dimethoxy-4- (methoxycarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-trifluoromethoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methyl-5-aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (4-cyanophenyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-nitro-4-aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-methylphenox) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (methoxycarbonyl) methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((carbazol-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-oxo-l, 3-benzothiol-2-on-6-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-phenyl-1-4-oxo-4-l-l-benzopyran-3-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-oxo-4-methyl-2i? -l-benzopyran-7-yl) oxy) methyl) carb? Nyl-4- (4-chlorobenzyl) piperazine; 1- ((4-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-carboxy-4-aminophenoxy) methyl) carbonyl-4- (4'-chlorobenzyl) piperazine; 1- ((2-methoxy-5-aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-phenyl-4-oxo-2,3-dihydro-4-l-l-benzopyran-6-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((quinolin-6-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,3-diaminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (hydroxysulfonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((fluorenon-9-on-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((5-, 6, 7, 8-tetrahydronaphthalen-1-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((5, 6, 7, 8-tetrahydronaphthalen-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4-, 6-tribromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dibromo-4-cyanophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-fluorophenoxy) methyl) c.arbonyl-4- (4-chlorobenzyl) piperazine; - ((2,3,5,6-tetrafluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2,6-difluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2,3-dichlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2, 3, 6-trichlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-chloro-4,5-dimethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,5-dichlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-chloro-5-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (methylcarbonyl) aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-isopropoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (benzyloxy) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piper zine; 1- ((2-ethoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-phenylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (methoxycarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, 1- ((2- (ethoxycarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-acetylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (ethylcarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; ! - ((2- (t-butyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-isopropylphenoxy) -methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (1-methylpropyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,3-dimethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,3,5-trimethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; ((2, 3, 6-trimethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4-dimethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2 , 4,6-trimethoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2-methyl-5-isopropylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2, 5 -dimethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; l- ((2,5-dimethyl-4- (diethylamino) methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (( 2- (t-butyl) -6-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dimethoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; ((2-prop-3-enyl-6-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-prop-2-enylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-ethylphenoxy) methyl) carbonyl-4- (4-chlorobenzene) il) piperazine; i-1 (2 -? - propylphenoxy) metii) carbor.?l-4- (4-chlorobenzyl) piperazine; 1- ((3-fluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (3, 5-difluorophenoxy) methyl) arbonyl-4- (4-chlorobenzyl) pi-perazine; 1- ((3-chloro-4-fluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; l-i .3, 5-dichlorophenoxy) me il; carbcnyl-4- (4-chlorobenzyl) piperazine; 1- ((3-iodophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3- (phenylamino) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3- (diethylamino) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-phenylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-acetylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-trifluoromethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-t-butylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazole; i- ((3-isopropylphenoxy) methyl) carbonyl- - (4-chlorobenzyl) piperazine; I- ((3-methy1-4-acetylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3, -dimethylphenoxy) methyl) carbonyl-4- (-chlorobenzyl) piperazine; 1- ((2-t-Butyl-5-methylphenoxy) methyl) carbonyl-4- (4-ciorobenzyl) piperazine; 1- ((2-isopropyl-5-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-ethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dimethyl-4-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dibromo-4-fluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-bromo-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methyl-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-isopropyl-4-chloro-5-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- f 4- (methylcarbonyl) aminophenoxy) methyl) carbonyl- (4-chlorobenzyl) piperazine; 1- ((-e-oxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-propoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-n-butoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; i- i (-n-hexo? ifenoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; ! - ((4-n-heptoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (propoxycarbonyl) phenoxy) methyl) carbonyl-4 ~ (4-chlorobenzyl) piperazine; 1- ((4- (ethylcarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (1, 1, 3, 3-tetramethylbutyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (1, 1-dimethylpropyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (1-methylpropyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-acetyl-4-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (butyl) -methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3- (ethylamino) -4-methylphenoxy) methyl) carbonyl-4- (4- (chlorobenzyl) piperazine; 1- ((4- (methoxycarbonyl) methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl; pip? Aain; 1- ((4-ethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-n-propylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; ! - ((2-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-4,6-dibromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-4,6-dichlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-4,6-diiophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-6-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-6-methylphenoxy Imeti]) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-5-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-5-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((2-carboxy-5-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; ((2-carboxy-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-4-fluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; (2-carboxy-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-4-iodophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; (2 ~ carboxy-4-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2, 3 , 4-trichlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2, 3,4,5,6-pentachlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ( (2,4,5-trichlorophenoxy) methyl) carbonyl-4- (4- clo) robencil) piperazine; 1- ((3-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (5- (methoxycarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3- (ethoxycarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl piperazine; 1- ((4-bromophenoxy) methyl) carbonyl-4- (-chlorobenzyl) piperazine; 1- ((2,6-dimethyl-4-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3,5-dimethyl-4-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-methyl-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; . 1- ((2-isopropyl-4-chloro-5-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; I- ((4-ethoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; l- ((2- (-butyl) -4-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (3-formyl-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4-prop-3-enylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; i- ((2- (1-phenylethyl) -4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (ethoxycarbonyl) methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - v > . -trifluoromethoxyfenc-xi methyl / carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-fluoro-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-fluoro-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((7-methoxynaphthalen-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-benzyloxy-4-cyanophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-chloro-3, 5-dimethoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-bromo-3,5-dimethoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3,5-dimethoxy-4-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dibromo-3,5-dimethoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (2-methy1-3-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) pexazxn; 1- ((3,5-dimethoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-3-carboxy-6-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-cyanophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-5-nitrophenuxi) methyl) carbonii-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-5-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3- (carboxymethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-5-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; i- ((4- (dimethylamino) methylphenoxy) methyl) carbonyl-4- (4-ciorobenzyl) piperane; i- ((4- (2- (dimethylamino) ethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-carboxyphenoxy) me il) carbonyl- - (4-chlorobenzyl) piperazine; (. {(Naphthalen-1-ii) oxy) methyl) carbonyl-4- (4-chlorobenzyl piperazine; I- (t (5-aminonaf alen-i-yl) oxy) me il) carbonyl-4- (4- chlorobenzyl) piperazine; 1- ((3-nitro-4-aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-di (t-butyl) -4-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-carboxy-4-nitrophenoxy) methyl) carbonyl-4- (4-lorobenzyl) piperazine; 1- ((2-methyl-5-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-4-aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (benzyloxy) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- . { (4- (aminocarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) p ± perazine; 1- ((3,5-di (trifluoromethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2, -dibromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dibromo-4-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazm; 1- ((2, -dichlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl; pip ratine; 1- ((3-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3,5-dimethyl-4-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3,5-dicarboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-chloro-4-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dichloro-4-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-carboxyquinolin-4-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; i- ((2,6-dimethyl-4-formylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-di (t-butyl) -carboxyphenoxy) methyl) carbonyl- (4-chlorobenzyl) piperazine; 1- ((2-amino-5-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; -f (2,6-di (-butyl) -4- (hydroxymethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - (((4-carboxyquin! In-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((3-nitro-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; l- ((3-ethyl-4-chloro-5-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3,5-di (methoxycarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (morpholin-4-yl) methyl-4-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine 1- ((2-methoxy-4-cyanophenoxy) methyl) carbonyl-4 - (4- chlorobenzyl) piperazine; 1- ((2-chloro-4-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-trifluoromethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) pyrazine; 1- ((2-methyl-acetylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3- (dimethylamino) phenoxy) methyl) carbonyl- - (4-chlorobenzyl) pipera? Ina; 1- ((3-methyl-4-acetylfenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3,5-dimethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-phenylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (ethoxycarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-acetylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-benzy-phenoxy) me-cyclic) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((3-carboxynaphthalen-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (hydroxymethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (1 (quinolin-8-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((4- (aminocarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((3,5-dimethoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; -. { (2- (cyclohexyl) phenyl) -me il) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((quinolin-6-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4-dichloro-3-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,5-dimethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3- (methylcarbonyl) aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-acetylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-trifluoromethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-formylphenoxy) methyl carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-5-formylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ( ((tropinon-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl; piperazm; 1- ((2-nitro-5-fluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-5-formylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-formyl-4-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-5-nitrophenoxy) methyl) carbonii-4- (4-chlorobenzyl) piperazine; 1- ((2-amino-4-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-amino-3-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-4-aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dichloro-4-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; i- ((3-fluoro-4-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,3-difluoro-6-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-chloro-4-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; i- ((2-nitro-4-cyanophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-bromo-4-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-chlorophenoxy) methyl) carbonyl-4 ~ (4-chlorobenzyl) piperazine; 1- ((3,4-dichlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; __ 1- ((3,5-dichlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3,, 5-trimethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-fluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3,5-dimethyl-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (methoxycarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-trifluoromethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-t-butylphenoxy) methyl) carbonyl-4- (4-clcrobenzyl) piperazine; 1- ((4-isopropylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((naphthalen-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) 'piperazine; 1- (((6-bromonaphthalen-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3- (hydroxymethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-5- (hydroxymethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((1,3-benzodioxolan-5-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dimethyl-4-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4- (amino) methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((3- (aminocarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((3- (methoxycarbonyl) methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ("" (1- (4-phenylcarbonyl) -4-fluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; 1- ((2- (1-methyl) cyclohexyl-2,4-dimethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; 1- ((2- (benzyloxycarbonyl) phenoxy) methyl) carbonyl-4- (4-fiuorobenzyl) piperazine; 1- ((2- (4- (methyl) phenylcarbonyl) -5-methoxyphenoxy) methyl) carbonyl-4- (4-fiorobenzyl) piperazine; 1- ((2-phenylcarbonyl-5-octoxyphenoxy) methyl) carbonyl-4- (4-fluorobenzyl) piperazine; 1- . { (4-octylphenoxy) methyl) carbonyl-4- (4-fluorobenzyl) piperazine; 1- ((2- (2- (carboxy) phenylcarbonyl-5-di (n-butyl) aminophenoxy) methyl) carbonyl-4- (4-fluorobenzyl) piperazine; 1- ((2-phenylcarbonyl-5-methoxyphenoxy) methyl) ) carbonyl-4- (4-F) uorobenzyl) piperazine; 1- (2-methoxy-4- (3-hydroxyprop-2-enyl) phenoxy) methyl) carbonane-4- (4-fluorobenzyl) piperazine; 1- . { ((3- (phenylaminocarbonyl) naphthalen-2-yl) oxy) methyl) carbonyl-4- (4-fluorobenzyl) piperazine; 1- (((6- (phenylcarbonyl) naphthalen-2-yl) oxy) methyl) carbonyl-4- (4-fluorobenzyl) piperazine; 1- ((2- ((2-phenylethyl) carbonyl) phenaxy) methyl) carbonyl-4- (-fluorobenzyl) iperazine; l- ((4- ((4-f luorofenyl) carbonyl) phenoxy) raethyl) sarbonyl-4- (4- fluorobepcilj ipsrazir.a 1- ((2- (f eniJ.a? dí) carbonij. euo? i / roetil) carbon 11-4- (4- f luorobenzyl) iperazine 1- ((2 * = phenyl aralonyl) oxy) eyl) carbonyl ~ 4- (4- f luoroljerjci J.) pipera zina; 1- ((2-Fepylcarbonyl-4-chloro-5-methyl-phenoxy) -methyl) -carbonyl-4- (4-fluorobenzyl) -perazine; 1- (4- (4-chlorophenyl) earbonylf-enoxy) methyl) carbonyl-4- (4-fl? O -benzyl) piperazine; 1-1 (4-benzylane oriyl) phenoxy Inul) sarbopil-4- (- fluoro-pynoyl-iperazine; 1- ((2-phenylcarbonyl-4-aethyl-4-yl) p-styl) -carbonyl-4- (4 - f luorobortcil) piperazine; 1- ((4- (2-ei: ylcarbonylethyl) phenoxy) silyl) carbonyl-4- (4-pheurobenzyl) piperazine; l- [(4-phenylcarboyl) phenoxy) methyl) carboneyl-4- (4-fluorobenzyl) piperazine; and 1- ((3-f-enylcarbonylf-enoxy) -α-acetyl) carbonyl-4 ~ (- fluorobenzyl) piperazine; D. similarly, the following compounds of formula were prepared (la) or (Ib): methyl ester of 5-sloro-2- J2-f { 2R, 5S) -4- [(4-fluoro- phenyl) methy] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzoic acid; X H NMR (400 MHz, DMSO-d ^): d / ppm = 0.86-1.02 (m, 3H), 1.04-1.36 (m, 3H), 2.16 (m, 1H) , 2.62 (m, HH), 2.94 (m, 1H), 3.08 (m, 0.5H), 3.42 (m, HH), 3.58 (m, HH), 3, 76 (s, 3H), 3.98 (m, ÍH), 4.40 (s, 0.5H), 4.82 (m, 1.5H), 5.02 (m, 0.5H), 6.98 (s, 1H), 7.14 (m, 2ti) , 7.38 (m, 2H), 7.56 (m, ÍH), 7.62 (s, 1H) .- 5-bromo-2- [2- [(2R, 5S) -A-methyl ester [* (4-fluoro-phenyl) methyl] -2,5-dimethylpiperazinyl] -2-. oxoethoxy] benzenacetic; 1 H NMR (400 MHz, CDC13): .d / ppm = 0.90 (m, 3H), 1.30 (m, 3H), 2.25 (d, ÍH), 2.68 (d, 1H), 3.00 (m, HH), 3.20 (m, HH), 3.40- (m, 1H), 3.50 (m, 2H), 3.62 (s, 2H), 3.68 ( s, 3H), 4.65 (m, 3H), 6.80 ,. 1H) .. 7.00 (t, 2H), 7.30 (m, 4H). '5-bromo-2- [2- [(2R) -4 - [(4-fluorophenyl) methyl] -2-methyl-piperazinyl] -2-oxoethoxy] encenacetic acid methyl ester; : H NMR (400 MHz, CDC13):. d / ppm = 1.30 (m, 3H), 2.00 (m, ÍH), 2.10 (ra, ÍH), 2.60 (d, ÍH), 2.80 (m, HH), 3.45 (m, 2H), 3.60 (m, 2H), 3.62 (s, 3H), 4.30 (m, 1H), 4.65 (m, 2H) , 4.75 (d, 2H), 6.78 (d, "? - i-nr 1. 7u> -7 7 n 1". I "5-bromo-2- [2- [(21? 5S) -4- [(4-fluorophenyl) methyl] methyl ester ] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzoic acid; . ZH NMR (400 MHz, DMSO-de):. d / ppm »0.76-0.98 (m, 3H), 1.08-1.30 (m, 3H), 2.16 (m, HH), 2.62 (m, HH), 2, 94 (m, ÍH), 3.08 (m, 0.5H), 3.58 (m, 3H), 3.73 (s, 3H), 4.00 (m, ÍH) ', 4.40 (s, 0.5H), 4.88 (m, 1.5H), 5.08 (m, 0.5H) _, 6.96 (m, HH), 7.14 (m, 2H), 7.36 (m, 2H), 7.66 (m, 1H), 7.84 (m , ÍH). 5-bromo-2- [2- [. { 2R, 5S) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] -4-methoxybenzoic acid; XH NMR (400 MHz, DMSO-de) :. d / ppm = 0.76-0.97 (m, 3H), 1.08-1.32 (m, 3H), 2.16 (m, HH), 2.62 (m, HH), 2, 94 (m, HH), 3.08 (m, HH), 3.40 (m, 1.5H), 3.58 (m, HH), 3.73 (s, 3H), 3.87 (s, 3H), 4.00 (m, 1H), 4.40 (s, 0.5H), 4.92 (m, 1.5H), 5.08 (m, 0.5H) , 6.68 (m, ÍH), 7.14 (m, 2H), 7.36 (m, 2H), 7.86 (s, ÍH). 5-chloro-2- [2- [(2R, 5S) -A - [(4-fluoro-phenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] -4-methoxybenzoic acid methyl ester; H NMR (500 MHz, DMSO-d6):. d / ppm = 0.90 (m, 3H), 1.25 (m, 3H), 2.23 (m, 1H), 2.75 (m, 2H), 2.94 (m, 1H), 3 , 35 (m, 1H), 3.45 (m, ÍH), 3.63 (m, ÍH), 3.77 (s, 3H), 3.92 (s, 3H), 4.31 (s, ÍH), 4.92 (m, 2H), 6.81 (s, ÍH), 7.12 (m, 2H), 7.37 (m, 2H), 7.72 (s, ÍH). 5-chloro-2- [2- [(21? 5S) -4- [(4-fluoro-phenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] -4-methylbenzoic acid methyl ester; XH NMR (400MHz, CDC13):. d / ppm = 0.78-0.98 (m, 3H), 1.18-1.36 (m, 3H), 2.22 (m, 1H), 2.33 (s, 3H), 2, 66 (m, ÍH), 3.00 (m, ÍH), 3.10-4.20 (m, 4H), 3.86 (s, 3H), 4.24-4.86 (m, 3H) 6.94-7.02 (m, 3H), 7.29 (m, 2H), 7.81 (s, ÍH). 4,5-dichloro-2- [2- [(21? 5S) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzoic acid methyl ester; XH NMR (400 MHz, CDC13):. d / ppm = 0.91 (d, 3H), 1.29 (d, 3H), 2.24 (d, ÍH), 2.69 (dd, 1H), 3.02 (br, 1H), 3 , 41 (d, 1H), 3.47-3.71 (m, 2H), 3.87 (s, 3H), 4.10-4.22 (m, 1H), 4.60-4.86 (m, 3H), 7.00 (dd, 2H), 7.18 (br, ÍH), 7.30 (dd, 2H), 7.91 (s, 1H). 5-chloro-2- [2- [(2i? 5S) -4- [(4-fluoro-phenyl) methyl] -2,5-dirnethylpiperazinyl] -2-oxoethoxy] -4- (trifluoromethyl) acid methyl ester benzoic; 1 'NMR (400 MHz, CDCl 3): .d / ppm = 1.00 (m, 3H), 1.30 (m, 3H), 2.25 (d, 1H), 2.70 (dd, 1H) , 3.05 (m, ÍH), 3.20 (ra, ÍH), 3.50 (m, 2H), "3.68 (m, ÍH), 3.95 (s, 3H), 4.20 (m, HH), 4.80 (m, 2H), 7.00 (t, 2H), 7.30 (m, 3H), 7.90 (s, HH), 5-chloro-2-methyl ester - [2- [(2R, 55) -2,5-Diethyl-4- [(4-fluorophenyl) methyl] piperazinyl] -2-oxoethoxy] benzoic acid; 2 H NMR (400 MHz, DMSO-d 6):. d / ppm = 0.62 (m -.rotamer, 1.25H), 0.73 (t-rotamer, 3.5H), 0.85 (m-rotamer, 1.25H), 1.23 (m, HH), 1.37 (m, 1H), 1.55 (m, HH), 1.70 (m, 1H), 1.83 (m, HH), 2.26 (t, 1H), 2, 55 (d, ÍH), 2.75 (d-rotamer, ÍH), 3.45 (dd, ÍH), 3.47 (t, ÍH), 3.60 (m, 1H), 3.78 (s, 3H), 4.20 (d, ÍH), 4.90 (m - rotamer, 2H), 6.99 (d, ÍH), 7.13 (t, 2H), 7.35 (t, 2H), 7.55 (dd, 1H), 7.64 (d, ÍH) . 5-brorao-2- [2- [(2R, 5S) -2,5-diethyl-4- [(4-fluorophenyl) methyl] piperazinyl] -2-oxoethoxy] -4-methoxybenzoic acid methyl ester; . X H NMR (400 MHz, DMSO-d 6):. d / ppm = 0.60-0.90 (m, 6H), 1.06-1.60 (m, 3H), 1.62-1.82 (m, 1.5H), 2.16 (m , ÍH), 2.60 (m, 2H), 2.88 (m, HH), 3.46 (m, HH), 3.60 (m, 1.5H), 3.76 (s, 3H) , 3.85 (s, 3H), 4.22 (m, ÍH), 4.92 (m, ÍH), 5.12 (m, ÍH), 6.68 (m, ÍH), 7.12 (m, 2H) , 7.34 (m, 2H), 7.86 (s, 1H). -bromo-2- [2- [(2R) -4- [(5-chloro-2-thienyl) methyl] -2-methylpiperazinyl] -2-oxoethoxy] benzeneacetic acid methyl ester; 1ti NMR (400 MHz, -CDC13):. d / ppm = 1.30 (m, 3H), 2.05 (m, HH), 2.15 (m, HH), 2.75 (m, .1H), 2.90 (m, HH), 3.05 (m, ÍH), 3.45 (m, ÍH), 3.60 (m, 2H), 3.65 (s, 2H), 3.70 (s, 3H), 4.35 (m, ÍH), 4.68 (m, 2H), 6.65 (d, ÍH), 6, 72 (d, ÍH), 6.80 (dd, ÍH), 7.35 (m, 2H). 5-chloro-2- [2- [(21? 5S) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzenesulfonic acid; H NMR (400 MHz, DMSO-dg): d / ppm = 0.73-0.88 (m, 3H), 1.12-1.25 (m, 3H), 2.05-2.20 (m , ÍH), 2.65 (m, HH), 2.90 (m, HH), 3.08 (m, 0.5H), 3.50- (m, 3H), 3.97 (m, 0 , 5H), 4.40 (m, 1H), 4.75 (m, 1.5H), 4.94 fm, 0.5H), 6.93 (m, 1H), 7.12 (m, 3H) ), 7.34 (m, 3H) ', 7.57 (m, ÍH). 5-chloro-2- [2- [(21?) -4- [(4-fluorophenyl) methyl] -2-methylpiperazinyl] -2-oxoethoxy] benzenesulfonic acid; . 1R NMR (400 MHz, DMSO-d £ + TFA): d / ppm = 1.16 (d, 3H), 1.32 (d, 3H), 2.76-3.50 (m, 5H), - 4, 24-4, 52 (m, 3H), 4.60-5.00 (m, 3H), 6.50 (m, HH), 7.23 (m, 2H), 7.30 (m, HH), 7.54 (m, 2H), 7 , 67 (m, ÍH), 9.50 (br, ÍH). EXAMPLE 3 Compounds of Formula (Ia) and Formula (Ib) A. To a solution of 1- ((3,4-, 5-trimethoxyphenoxy) methyl) -carbonylpiperazine (0.22 g, 0.70 mmol) in acetic acid 1% in methanol (6 mL) was added 4-cyanobenzaldehyde (0.33 g, 2.5 mmol) and sodium cyanoborohydride (0.093 g, 1.4 mmol). The resulting mixture was stirred at room temperature for 1.5 hours and the mixture was then concentrated in vacuoles. The residue was taken up in ethyl acetate and washed with saturated aqueous NaH-C03 solution, water, and then brine. The organic layer was separated, dried over MgSO4, filtered and concentrated in vacuo to give a yellow oil. Purification by column chromatography on silica gel gave 0.21 g of 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-4- (4-cyanobenzyl) piperazine, a compound of formula (Ib) , as a limpid oil: NMR (CDCl 3) 7.6 (d, 2), 7.4 (d, 2), 6.2. (s, 2), 4.6 (s, 2), 3.8 (s, 6), 3.75 (s, 3), 3.6 (m, 4), 3.5 (s, 2) , 2.2 (m, 4) ppm. B. similarly, other form (Ib) compounds were prepared: 1- ((3,, 5-trimethoxyphenoxy) methyl) carbonyl-4- (3,4-dimethoxybenzyl) piperazine; 1- ((3,4,5-trim oxy phenoxy) methyl) carbanyl-4- (4-methoxybenzyl) piperazine, 1- ((3,4,5-trimethoxyphenoxy) -ethyl) carbonyl-4- (3-chlorobenzyl) piperazine; 1- ((3, 4, 5-trimethoxyphenoxy) methyl) carbonyl-4- (3-trifluoromethylbenzyl) piperazine; 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-4- (2,3-dimethyl-4-methoxybenzyl) piperazine; 1- ((3, 4, 5-trimethoxyphenoxy) methyl) carbonyl-4- (3-phenoxybenzyl) piperazine; 1- ((3, 4, 5-trimethoxyphenoxy) methyl) carbonyl-4- (4- (dimethylamino) benzyl) piperazine; 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-4- (4- (methylthio) benzyl) piperazine; 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-4- (4-methoxy-3-methylbenzyl) piperazine; 1- ((3, 4, 5-trimethoxyphenoxy) methyl) carbonyl- (2-chlorobenzyl) piperazine; 1- ((3, 4, 5-trimethoxyphenoxy) methyl) carbonyl-4- (3-nitrobenzyl) piperazine; i- ((3,, 5-trimethoxyphenoxy) me ii) carbonyl-4- (4'-hydroxybenzyl) piperazine; - ((3, 4, 5-trimethoxyphenoxy) methyl) carbonyl-4- (3,5-dibromo-4-hydroxyben) piperazine; 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-4- (2-fluorobenzyl) piperazine; 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 2), 7.0 (m, 2), 6.2 (s, 2), 4, 6 (s, 2), 3.9 (m, 9), 3.6 (m, A), 3.4 (s, 2), 2.4 (m, 4) ppm; 1- ((3, 4, 5- trimethoxyphenoxy) methyl) carbonii-4- (4-bro or -benzyl) piperazine; NMR (CDC13) 7.4 (d, 2), 7.2 (d, 2), 6.2 (s, 2), 4.6 (s, 2), 3.85 (s, 6), 3 , 75 (s, 3), 3.6 (m, 4), 3.4 (s, 2), 2.4 (m, 4) ppm; 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-4- (2-bromobenzyl) piperazine; 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-4- (3-fluorobenzyl) piperazine; 1- . { (3, 4, 5-trimethoxyphenoxy) methyl) carbonyl-4- (3-bromobenzyl) piperazine; i- ((3, 4, 5-trimethoxyphenoxy) methyl) carbonyl-4- (3-cyanobenzyl) piperazine; - ((3, 4, 5-trimethoxyphenoxy) methyl) carbonyl-4- (2,4-difluorobenzyl) piperazine; 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-4- (2, 3-difluorobenzyl) piperazine; -. { (3,4,5-trimethcxyphencxyme il) carbonyl-4- (3,4-difluorobenzyl) piperazine; NMR (CDCl 3) 7.3-7.0 (m, 3), 6.2 (s, 2), 4.6 (s, 2), 3.85 (s, 6), 3.75 (s, 3), 3.6 (m, 4), 3.5 (s, 2), 2.4 (m, 4) ppm; 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-4- (2,6-difluorobenzyl) piperazine; 1- ((3, 4, 5-trimethoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; NMR (CDC13) 7.2 (m, 4), 6.2 (s, 2), 4.6 (s, 2), 3.85 (s, 6), 3.75 (s, 3), 3 , 6 (m, 4), 3.5 (s, 2), 2.4 (m, 4) ppm; 1- ((3, 4, 5-trimethoxyphenoxy) methyl) carbonyl-4- (3-chloro-4-fluorobenzyl) piperazine; 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-4- (4-trifluoromylbenzyl) piperazine; 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-4- (4-nitrobenzyl) piperazine; 1- . { (3,4,5-trimethoxyphenoxy) methyl) carbonyl-4- (4-fluorobenzyl) piperazine; 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-4- (2,5-difluorobenzyl) piperazine; 1- ((3, 4, 5-trimethoxyphenoxy) methyl) carbonyl-4- (3-nitro-4-hydroxybenzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-4- (-fluorobenzyl) piperazine; NMR (CDCi3) 7. 2 (m, 4), 7.0 (t, 2), 6.8 (d, 2). 4.6 (s, 2), 3.6 (m, 4), 3.4 (s, 2), 2.4 (m, 4) ppm; 1- ((-chlorophenoxy) methyl) carbonyl-4- (-chlorobenzyl) piperazine; NMR (CDC13) 7.2 (m, 6), 6.8 (d, 2), 4.6 (s, 2), 3.6 (m, 4), 3.5 (s, 2), 2 , 4 (m, 4) ppm; 1- ((3, 4, 5-trimethoxyphenoxy) methyl) carbonyl-4- (3- (benzyloxy) benzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-4- (3,4,5-trimethoxybenzyl) piperazine; C. similarly, the following compounds of formula (la) were prepared: (3S) -1- ((4-chlorophenoxy) methyl) carbonyl-3-methyl-4- (4-fluorobenzDpiperazine; NMR (CDCl3) 7.3 (m, 4), 7. 0 (t, 2), 6.9 (d, 2), 4.6 (s, 2), 4.0 (m, 2), 3.7 ym, 1), 3.4-2.9 ( go., 3), 2. 7 (m, 1), 2.5 (m, 1), 2. 1 (m, 1), 1.1 (m, 3) ppm; (31?) -1- ((4-chlorophenoxy) methyl) carbonyl-3-methyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.6 (s, 2), 4.0 (m, 2), 3 , 7 (m, 1), 3,4-2,9, m, 3), 3,2, m, 1), 3,0 (m, 1), 2. 7 (m, 1), 2.5 (m, 1), 2.1 (m, 1), 1.1 (m, 3) ppm; 1- ((4-chlorophenoxy) methyl) carbonii-3- (2- ((((4-chlorophenoxy) methyl) carbonyl) oxy) ethyl) -4- (4-fluorobenzyl) piperazine; - ((4-chlorophenoxy) methyl) carbonyl-2-hydroxyethyl-4- (4-fluorobenzyl) piperazine, dihydrochloride salt; - ((4-chlorophenoxy) methyl) carbonyl-2- (2- ((2-methylpropyl) amino) ethyl) -4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.1 (m, 4), 6.9 (t, 2), 6.7 (d, 2), 4.6 (s, 2), 4.4 (d, 1), 3, 6 (d, 1), 3.3 (m, 3), 2.7-2.3 (m, 6), 2.0-1.7 (m, 5), 0.8 (t, 6) ppm; - ((4-chlorophenoxy) methyl) carbonyl-2- (2- ((4-fluorobenzyl) amino) ethyl) -4- (4-fluorobenzyl) piperazine ,. hydrochloride salt; - ((4-chlorophenoxy) methyl) carbonyl-2- (2- ((2-hydroxyethyl) amino) ethyl) -4- (4-fluorobenzyl) piperazine; - ((4-chlorophenoxy) methyl) carbonyl-2- (2- ((methyl) amino) ethyl) - (4-fluorobenzyl) piperazine; - ((4-chlorophenoxy) methyl) carbonyl-3- (2- ((4-fluorobenzyl) amino) ethyl) -4- (4-fluorobenzyl) piperazine, hydrochloride salt; - (4-chlorophenoxy) methyl) carbonyl-3- (2- ((methyl) amine) ethyl) -4- (4-fluorobenzyl) piperazine; - ((4-chlorophenoxy) methyl) carbonyl-3- (2- ((2-hydroxy-ethyl) amino) ethyl) -4- (4-fluorobenzyl) piperazine; - ((4-chlorophenoxy) methyl) carbonyl-3- (2- ((2-methylpropyl) amino) ethyl) -4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (((ethyl) amino) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 4), 7.0 (d, 2), 6.9 (t, 1), 6.4 (br s, 2), 5.0-4.6 (m , 3), 4.0 (m, 3), 3.7- 3.2 (m, 4), 3.0-2. 7 (m, 3), 2.2 (m, 1), 1.3 (m, 6), 1.0 (br d, 3) ppm; (trans) -1- ((4-chloro-2- (. {((diethyl) amino) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.5 (d, 1), 7.3 (m, 2), 7.2 (dd, 1), 7.0 (t, 2), 6.8 (d, 1), 4.7 (m, 3), 4.2 (m, 1), 3.6-3 , 4 (m, A), 3.2_ (m, 1), 3.0 (m, 1), 2. 7 (dd, 1), 2.6 (q, 2), 2.2 (d, 1), 1.3 (m, 3), 1.0 (m, 9) ppm; . { rans) -1- ((4-chloro-2- (((cyclopropyl) amino) methyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 7.3 (m, 4), 7.0 (d, 2), 6. 8 (t, 1), 4.8-4.0 (m, 6), 3.7-3.2 (m, 3), 3.0 (br s, 1), 2. 7 (d, 1 ), 2.2 μm, 2), 1.3 (m, 3), 0.9 (m, 3), 0.5 (m, 4) ppm; (trans) -1- ((4-chloro-2- (((dimethyl) amino) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; RMM (CDCl;.) 7.3 (m, 4), 7.1 (dd, 1), 7.0 (t, 2), 6.8 (d, 1), 4.7 (m, 3) , 4.1 (m, 1), 3.6-3.4 (m, 4), 3.0 (br s, 1), 2.7 (dd, 1), 2.2 (m, 8) , 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- (((methyl) amino) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 7.3 (m, 4), 7.1 (dd, 1), 7.0 (t, 2), 6.8 (d, 1), 4.7 (m, 2), 4.1 (m, 1), 3.7-3.4 (m, 5), 3.0 (br s, 1), 2.7 (dd, 1), 2.4 (s, 3), 2.2 (m, 2), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- ((amino) methyl) phenoxy) methyl) carbonane-2, 5-dimethyl-4- (4-luorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 4), 7.1 (dd, 1), 7.0 (t, 2), 6.7 (d, 1), 4.7 (m, 2), 3 , 8 (d, 1), 3.5 (m, 4), 3.0 (br s, 1), 2.7 (dt, 1), 2.2 (d, 1), 1.3 (m , 3), 0.9 (m, 3) ppm; α trans) -1- ((4-chloro-2- ((4-methylpiperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 7.3 (m, 4), 7.1 (dd, 1), 7.0 ít, 2, 6.8 (d, 1), 4.7 (m, A), 4, 2 (m, 1), 3.8 (m, 1 ¡, 3.6-3.0 (m, 8), 2.9 (t, 1), 2.7 (m, 1), 2. 5-2.2 (m, 6), 1.3 (m, 3), 0.9 (m, 3) ppm; zrans) -1- ((4-chloro-2- (piperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 7.9 (m, 3), 7.7 (s, 2). 7.4 (t, 1), 7.2 (m, 2), 5.4 (d, 1), 5.0 (m, 2), 4.3 (m, 4), 3. 6-3 , 1 (m, 12), 2.8 (m, 1), 1.5-1.0 (m, 6) ppm; (trans) -1- ((4-chloro-2- (((2-hydroxyethyl) amino) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 7. 3 (m, 4), 7.1 (dd, 1), 7.0 (t, 2), 6.7 (d, 1), 4.7 (m, 2), 4 , 2-3.4 (m, 6), 3.0 (br s, 2), 2.7 (m, 4), 2.2 (d, 2), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- ((morpholinyl) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 3), 7.1 (dd, 1), 7.0 (t, 2), 6.7 (d, 1), 4.7 (m, 2), 4 , 1-3.4 (m, 11), 3.0 (br s, 1), 2.7 (dd, 1), 2.5 (t, 4), 2.2 (d, 1), 1.3 (m, 3), 0 , 9 (m, 3) ppm; (trans) -1 - ((4-chloro-2- (ethylaminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) pyrrazine; NMR (CDC13) 7.3 (m, 3), 7.2 (dd, 1), 7.0 (t, 2), 6.8 (m, 1), 4.7 (m, 2), 4.1 (m, 1), 3.8 (s, 2), 3.6 (m, 1) , 3.5 (q, 2), 3.0 (m, 1), 2.7 (m, 2), 2.6 (q, 2), 1.3 (m, 3), 1.1 ( t, 3), 1.0 (m, 6) ppm; (trans) -1- ((4-chloro-2- ((ethyl) (1-methylbutyl) aminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 7.9 (ra, 1), 7.7 (m, 2), 7.5 (m, 1), 7.2 (m, 3), .1 (m, 1), 4.6 (d, 1), 4.3 (m, 2), 3.7-2.8 (m, 6), 2. 5 (s, 2), 1 , 5-1.2 (m, 19), 0.8 (s, 3) ppm; (trans) -1- ((4-chloro-2- (benzylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 7), 7.0 (t, 2), 6.7 (d, 1), 6.6 (m, 2), 4.7 (d, 2), 4.4 (s, 2), 4.2-3.0 (m, 8), 2.6 (dd, 1), 2.2 (d, 1) ), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1 - ((4-chloro-2- ((1-methylbutyl) amino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR-DMSO-d £) 7.9 (m, 2), 7.3 (t, 2), 7.1 (m, 1), 6.9 (d, 2), 5.2 (d, 1), 4.9 (m, 2), 4.6 (m, 1), 4.5-3.2 (m, 6) ), -2.8 (t, 1), 2.5 (s, 1), 1.7-1.2, 9), 0.9 (d, 6) ppm; (rans) -1- ((4-chloro-2- ("(cyclopropylmethyl) arninomethyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzDiperazine; NMR (CDCl3) 7. 3 ( m, 3) .7.1 (dd, 1), 7.0 (t, 2), 6.8 (br d, 1), 4.7 (m, 2), 3.5 (s, 2) , 3. € (m, 1), 3.5 (q, 2), 3.0 (m, 2), 2.7 (dd, 1), '2.4 (m, 3), 2.2 (d, 1), 1.3 (m, 3), 0.9 (m, A), 0.4 (m, 2), 0.1 (m, 2) ppm; (trans) -1- ( (4-chloro-2- (phenylaminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) pyrrazine; NMR (DMSO-d6) 7.8 (m, 2), 7.4 (m, 8), 7.2 (m, 2), 5.4 (d, 1), 5.0 (m, 2), 4.7 (m, 1), 4.5 (s, 2), 4. 3 (- ni, 2), 3.9-3.4 (m, 4), 1.4 (m, 3), 1.2 (m, 3) ppm; (trans) -1- ((4-chloro-2- (1- ((methyl) (ethyl) amino) ethyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) ) piperazine; NMR (CDC13) 7.4 (s, 1), 7.3 (m, 2), 7.1 (dd, 1), 7.0 (t, 2), 6.8 (br d, 1), 4.6 (br s, 3), 4.0 (m, 2), 3.6 (d, 1), 3.4 (d, 1), 3.0 (m, 1), 2.7 ( dd, 1), 2.5 (dq, 1), 2.4 (dq, 1), 2.2 (s, 3), 1.3 (m, 6), 1.0 (m, 6) ppm; (trans) -1- ((4-chloro-2- (1- (dimethylamino) ethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CD3OD) 7.6 (m, 3), 7.5 (d, 1), 7.3, 3), 5.1 (m, 3), 4, 4 (m, 2), 3, 8 (dd, 2), 3.6 (m, 1), 3.4 (m, 1), 3.0 (m, 1), '2.6 (m, 7), 1.6 (m, 6), 1.3 ym, 3) ppm; (2R) -l - '((4-chloro-2- ((4-t-butoxycarbonylpiperazin-1-yl) methyl) phenyl) r.etii'C3rbcnil-2-methyl-4- (4-fluo-robinyl) ) piperazine; NMR (CDC13) 7.3 (m, 3), 7.0 (t, 2), 6.8 (d, 1), 4.7 (m, 2), 4, 4 (m, 1 ), 3.5 (m, 10), 3.0 (m, 1), 2.8 (m, 1), 2.6 (m, 2), 1.4 (m, 12), 1.2 (m, 3) ppm; (trans) -1- ((4-chloro-2- ((4-butoxycarbonylpiperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4 - fluorobenzyl) piperazine; NMR (DMSO-d6) 7,8_ (rn, 2), 7,6 (s, 1), 7,5 (m, 1), 7,3 (t, 2), 7,2 (m, 1), 5.4 (d, 1), 5.0 (m, 2), 4.7 (m, 1), 4.3 (m, 6), 4.0 (m, 2) , 3.8-3.1 (m, 8), 2.9 (m, 1), 1.4 (m, 12), 1.2 (m, 3) ppm; 1- ((4-chloro-2- (morpholin-4-ylmethyl) phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 11. 5 (br d, y, _10.6 (m, 1), 7.7 (m, 2), 7.6 (s 1), 7.5 (dd, 1), 7.3 (t, 2), 7.2 (d, 1), 5.2 (qd, 2), 4.7 (m, 1), 4.4 (m, 4), 3, 9-3.7 (m, 4), 3.5 (m, 1), 3.4 (m, 4), 3.0 (m, 4), 2.8 (m, 1), 1.5 (d, 1.5), 1.3 (d, 1.5) ppm. 5-Chloro-4- (dimethylamino) -2- [2- [(2R, 5S) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzoic acid; X H NMR (400 MHz, DMSO-d 6):. d / ppm = 1.10-1.30 (m, 6H), 2.82 (s, 6H), 3.00 (m, HI), 3.21 (m, 0.5), 3.40 ( m, ÍH), 3.58-3.70 (m, 2H), 4.20-4.40 (m, 3H), 4.70 (ra, 0.5H), 4.90-5.10 (m , 2H), 6.62 (s, ÍH), 7.30 (t, 2H), 7.60 (m, 2H), 7.68 (m, ÍH). EXAMPLE 4 Compounds of Formula (Ia) A. To a solution of (21? 5JR) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fiuorobenzyl) -5- ( (hydroxy) methyl) piperazine (0.17 g, 0.42 mmol) in CH2C12 (50 mL) at 0 ° C was added triethylamine (excess) and methanesulfonyl chloride (0.050 mL, 0.5 mmol). The resulting mixture was stirred at 0 ° C until alcohol consumption was observed by TLC analysis. The mixture of volatiles was concentrated in vacuo. The residue was taken up in anhydrous DMF (5 mL) and K2CO3 (excess) was added, followed by tetrazole (0.050 g, 0.71 mmol). The resulting mixture was stirred a. room temperature for 3 days and filtered. The filtrate was concentrated in vacuo and the residue was taken up in ethyl acetate. This was washed with water, then brine, then dried over MgSO4 and concentrated in vacuo to give a yellow oil. Purification by column chromatography on silica gel gave 25 mg of '21?, 51?) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- (( tetrazolyl) methyl) piperazine as a white solid: NMR (CDC13) 7.3 (m, 5), 7.0 (m, 4), 4.8- 4.1 (m, 5), 3.8 (m , 3), 3.2 (m, 2), 2.8 (dd, 1), 2.5 (dd, 1), 1.4 (d, 3) ppm, MS (ESI) 458. B. in In a similar manner, the following compounds of formula (la) were prepared: (21? 51?) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- (( 1, 2, -triazol-2-yl) methyl) pyrazrazine; NMR (CDCl 3) 7.9 (s, 1), 7.3 (m, 5), 6.9 (m, 4), 4.7 (, 3), 4.4-3.4 (m, 5), 3.1-2.7 (m, 2), 2.4 (t, 1), 2.0 (d, 1), 1.2 (m, 3) ppm; Í21 ?, 5S) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((morpholin-4-yl) methyl) piperazine; NMR (CDC13) 7.3 (m, 4), 7.0 (t, 2), 6.8 (d, 2), 4.7-4. 1 . { m, 5), 3.9-3.4 (m, 9), 3.2-2.7 (, 3), 2.3 (m, 2), 2.0 (m, 1), 1.2 (m, 3) ppm; (2R, 5R) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl- - (4-fluorobenzyl) -5- ((piperazin-1-yl) methyl) piperazine; (21? 5S) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((diethylamino) methyl) piperazine; NMR (CDCl 3) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.7 (m, 3), 3.9-3. 4 (m, 4), 2.8-2.3 (m, 7), 1.2 (m, 3), 0.9 ít, 6) ppm; (2J ?, 55) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- (((ethyl) amino) methyl) piperazine; NMR (CDCl 3) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.7 (m, 3), 4.2-3.4 (m , 5), 2. 8-2.3 (m, 6), 1.3-1.0 (m, 6) ppm; (21 ?, 55) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorophenyl) -5- ((4-methylpiperazin-1-yl) methyl) piperazine; NMR (CDC13) 7. 3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.7 (m, 3), 3.9-3.4 (m, 4), 2.8-2.2 (m, 14), 1.2 (m, 3) ppm; 1- ((4-chlorophenoxy) methyl) carbonyl-4- (4-fluorobenzyl) -3- (2- (4- (-butoxycarbonyl) piperazin-1-yl) ethyl) piperazine, hydrochloride salt. { 21 ?, 55) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((dimethylamino) methyl) piperazine (21? 55) -1- ((-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- (((cyclopropyl) amino) methyl) piperazine (21? 55) -1 - ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((cyano) methyl) piperazine; NMR (CDCl 3) 7.3 (m, 4), 7.0 (m, 4), 4.6 (m, 4), 4.2-3.2 (m, 4), 2.6-2.2 m, 4), 1.2 m, 3) ppm; [2R, 55) -1- ((4-cycrophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((((cyclopropyl) methyl) amino) methyl) piperazine; (2i ?, 51?) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- (((2-hydroxyethyl) thio) methyl) piperazine; NMR (CDCl) 7.3 (m, 4), 7.0 (t, 2), 6.8 (d, 2), 4.7 (m, 3), 4.1-3. 5 (m, 5), 3.1-2.3 (m, 8), 1.3 (m, 3) ppm; _. (trans) -1- ((4-chloro-2- (imidazol-1-ylmethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 11.3 (m, 1), 9. 4 (s, 1), 7.9 (s, 3), 7.6 (s, 2), 7.4 (m, 1), 7.3 (m, 3), 7.1 (m, 1), 5.4 (m, 2) , 4.9 (m, 1), 4.2 (m, 2), 3.8-3.2 (m, 6), 2.7 (m, 1), 1.4-1.2 (m 6) ppm; . { trans) -1- ((4-chloro-2- (1- (imidazol-1-yl) ethyl) phenoxy) methyl) carboni 1-2.5-dimethyl-1-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 7.6 (s, 1), 7.3 (m, 2), 7.2 (dd, 1), 7.0 (m, 5), 6.8 (d, 1), 5.8 (q, 1), 4.6 (m, 3), 4.2 (m, 1), 3.5 (q, 2), 3.2 (m, 1), 3.0 (m , 1), 2. 7 (dd, 1), 2.2 (dd, 1), 2.0 (br s, 1), 1.8 (dd, 3), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-Chloro-2- (triazol-1-ylmethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 8.4 (s, 1), 7.9 (s, 1), 7 ', 3 (m, 3), 7.0 (t, 2), 6.8 (d, 1), 5.4 (s, 2), 4.6 (m, 3), 4.2 (m, 1), 3.5 (q, 2), 3.2 (m, 1), 3.0 (m , 1), 2.9 (dd, 1), 2.2 (dd, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; and (trans) -1- (4-chloro-2- (tetrazol-1-ylmethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) ^ (s, 1), 7.4 (s, 1), 7.3 (m, 3), 7.0 (t, 2), 6.8 (d, 1), 5.6 (s, 2), 4.7 (m, 3), 4.2 (m, 1), 3.5 (q, 2), 3.2 (m, 1), 3. 0 (m, 1) , 2.9 (dd, 1), 2.2 (dd, 1), 1.3 (m, 3), 0.9 (m, 3) ppm. EXAMPLE 5 Compounds of Formula (Ia) A. To a solution of oxalyl chloride (0.62 g, 5 mmol) in CH; C12 (20 mL) at -50 ° C was added DMSO (0.85 g, 11 mmol. , in 5 mL solution of CH 2 C 12) over 2 minutes. 4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxyethyl) piperazine (1.85 g, 4.5 mmol, in solution of 5 mL of CH;;). The resulting mixture was stirred at -50 ° C for 15 minutes, then triethylamine (2.3 g, 22 mmol) was added. After 5 minutes at -50 ° C, the mixture was gradually warmed to room temperature. At that time the mixture was diluted with CH2C12 and washed with water, then brine. The organic layer was then dried over MgSO4 and concentrated in vacuo to give 1.7 g of 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- ((formyl) methyl) piperazine as a yellow oil; NMR (CDC13) 9.8 (d, 1) 7.3 (m, 4), 7.0 (m, 4), 4.6 (m, 3), 3.8-3.2 (m, 7 ), 2.7-2.2 (m, 4) ppm. B. similarly, the following compounds of formula (la) were prepared: 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- ((acetylmethyl) piperazine, hydrochloride salt; (CDCl 3) 7.3 (m, 4), 6.9 (m, 4), 4.6 (m, 2), 3.8-3.3 (m, 7), 2. 4 (m, 4), 2.1 (d, 3) ppm; and (21 ?, 55) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methy1-5-formylpiperazine. EXAMPLE 6 Compounds of Formula (Ia) A. To a solution of 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- ((formyl) methyl) piperazine (0.31 g, , 77 mmol) in anhydrous THF (20 mL) was added methylmagnesium bromide (0.26 mL, 0.77 mmol, 3.0 M solution in ether). The resulting mixture was stirred overnight at room temperature. At that time the mixture was poured into NH4CI 5% aqueous solution and extracted with two portions of ether. The combined organic extracts were washed with brine, then dried over MgSO4, filtered and concentrated in vacuo to give a yellow oil. Purification by flash column chromatography on silica gel gave 0.29 g of 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3 ~ (2-hydroxypropyl) piperazine, as a clear and colorless oil, which was converted into its hydrochloride salt; NMR (CDCl 3) 7.6 (m, 2), 7. 2 (m, 4), 6.9 (m, 2), .4.7 (m, 2), 4.4-3.0 (m , 10), 2.4-1.4 (m, 2). 1.3-1. 0 (m, 3) ppm. B. similarly, the following compounds of formula (la) were prepared: 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxy-2-phenylethyl) piperazine; NMR (CDC13) 7.3 (m, 9), 7.0 (t, 2), 6.8 (d, 2), 4.9 (m, 1), 4.8 (m, .2), 4.1 (m, 1) ), 3.8-3.3 (m, 6), 2.8 (m, 2), 2.2 (m, 1), 2. 0 (m, 2) ppm; 4- (4-fluorobenzyl) -1- ((-chlorophenoxy) methyl) carbonyl-3- (2-hydroxypentyl) piperazine; NMR (CDC13) 7. 8 (m, 2), 7.3 (m, 4), 6, 9 (d, 2), 4.8 (d, 2), 4.5-3.0 (m, 16) 2.2-1.2 ( m, 8), 0.9 (m, 3) ppm; 4-α-fluorobenzyl) -1- ((-chlorophenoxy) methyl) carbonyl-3- (2-hydroxybut-4-enyl) piperazine; NMR (CDCl-3) 7'3 (m, 4), 7.0 (t, 2), 6.8 (d, 2), 5.7 (m, 1), 5.2 (dd, 1) , 5.1 (t, 1), 4.6 (m, 2), 4.2-3.3 (m, 7), 2, 9 (m, 2), 2.4 (m, 1), 1.9-1.5 (m, 2) ppm; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxy-2- (4-methylphenyl) ethyl) piperazine; (2R, 5R) -4 - (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5- (1-hydroxyprop-2-enyl) piperazine, hydrochloride salt; NMR (DMSO-d6) 10.1 (b s, 1), 7.6 (m, 2), 7.3 (d, 4), .6.9 (d, 2), 6.1 (m, 1), 5.9 (m, 1), 5.4 (m, 2), 4.8 (m, 2), 4.4 (m, 4), 3. 7-3 , 1 (m, 5), 1.1 (m, 3) ppm; (21? 51?) -4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5- (1-hydroxybutyl) piperazine, hydrochloride salt; PMN (MSO-d) 10.3 (bs, 1), 7.6, m, 2), 7.3 (m, 4), 6.9 (d, 2), 5.6 (m, 1) , 4.9 (m, 2), 4.4 (m, 3), 3.9-3.1 (m, 5), 1.4 (m, 4), 1.1 (d, 3), 0. 8 (t, 3) ppm; -. { 4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxybut-4-ynyl) piperazine; - (-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxy-2-cyclohexylethyl) piperazine; ZR, 5R) -4- (4-fluorobenzyl) -1- ((-chlorophenoxy) methyl) carbonyl-2-methyl-5- (1-hydroxyethyl) piperazine hydrochloride salt; NMR (DMSO-d6) 10.3 (bs, 1), 7.6 (m, 2), 7.3 (m, 4), 6.9 (d, 2), 5.6 (bs, 1) , 4.9 (m, 2), 4.6-4.0 (m, 6), 3.2 (m, 3), 1.2 (d, 3), 1.1 (d, 3) ppm; (21? 51?) -A- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5- (1-hydroxy-1- (phenyl) methyl) piperazine, hydrochloride salt; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-5- (2-hydroxy-2-methylpropyl) piperazine; (trans) -1- ((4-chloro-2- (1-hydroxyethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 3), 7.2-6.8 (m, 4), 5. 1 (m, 1), 4.7 (m, 2), 4.2-3, 0 (m, 9), 2.7 (dd, 1), 2.3 (d, 1), 1.5 (d, 3), 1.3 (br m, 3), 0.9 (br m , 3) ppm; 1- ((4-chlorophenoxy) methyl) carbonyl-2- (1-hydroxyethyl) -4- (4-fluorobenzDpiperazine; NMR (CDCl 3) 7.2 (m, 4), 7.0 μm, 2), 6.8 (dd, 2), 4.7 (m, 3), 4.2 (m, 1), 3.8 (m, 1), 3.4 (s, 2), 3.2 (m, 1), 2.3 (dd, 1), '2.1 (m, 1), 1.1 (m, 3) ppm; l- ((4-chlorophenoxy) methyl) carbonyl-2- (2-hydroxypropyl) -4- (4-fluorober.cil: piperazipa; NMR (DMSO-d e) 7.6 (br s, 2), 7, 3 (d, A), 6.9 (q, 2), 4.9 (m, 3), 4.3 (m, 3), 3.9 (m, 3), 3.3. (M, 2), 3.0 (m, 1), 2.2 (t, 1), 1.8 (m, 1), 1.5 (m, 1), 1. 1 (d, 1.5), 1.0 (d, 1.5) ppm; and 1- ((4-chlorophenoxy) -ethyl) carbonyl-2- (2-hydroxybut-3-enyl) -4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 7.6 (dt, 2), 7.3 (m, 4), 6.9 (t, 2), 5.8 (m, 1), 5.2 (dd, 1) , 5.0 (dt, 2), 4.8 (dt, 1), 4.4 (m, 2), 3.9 (m, 1), 3.4 (m, 3), 3.0 ( m, 3), 2.2 (m, 1), 1.8 (m, 1), 1.6 (m, 1) ppm. EXAMPLE 7 Compounds of Formula (Ia) A. To a solution of 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxy-2-phenylethyl) piperazine (0.051 g, 0.11 mmol) in anhydrous ether (5 mL) was added sodium hydride (0.006 g, 0.15 mmol). The resulting mixture was stirred at room temperature for 30 minutes, then methyl iodide (0.016 g, 0.11 mmol) was added. After the analysis by thin-layer chromatography showed that the total consumption of 4- (4-fluorobenzyl) -1- (4-chlorophenoxy) methyl) carbonane-3- (2-hydroxy-2-) had been produced. phenylethyl) piperazine, the mixture was poured into water and extracted with two portions of ether.

The combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo to give 0.046 g of 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-methoxy-2- phenylethyl) piperazine as a yellow oil: NMR (CDC13) 7. 3 (m, 9), 7.0 (m, 2), 6.9 (m, 2), 4.8 (m, 3), 4, 2 (m, 2), 3.9-3.2 (m, 5), 3. 1 (d, 2), 3.0 (s, i), 2.9 (s, 1), 2 , 6 (m, 1), 2.4 (m, 1), 1.9 (m, 1) ppm. B. similarly, other compounds of the invention were prepared: (21? 51?) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5- ((methoxy) methyl) piperazine; NMR (CDC13) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.6 (m, 3), 3.8-3.1 (m, 9), 3.0 (br s, 1), 2.7 (dd, 1), 2.3 (t, 1), 1.2 ym, 3) ppm; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (2- (methoxy) ethyl) piperazine; "NMR (CDCl 3) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.7 (m, 3), 4.1 (m, 1) , 3.7 (m, 1), 3.4-3.2 6), 2.8 (m, 3), 2.0 (m, 4) ppm; 4- (4-fluorobenzyl) -1- ( (-chlorophenoxy) methyl) carbonyl-3- (ethoxycarbonyl) methylpiperazin-2-one; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl: carbonypiperazin-2-one; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- ((methoxy) methyl) piperazine; NMR (CDC13) 7.3 (m, 4), 7.0 (t, 2), 6.9 (dd, 2), 4.7 (d, 2), 3.9-3. 3 (m, 11), 2.6 (m, 2), 2.2 (m, 1) ppm; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2- (methoxy) ethyl) piperazine; NMR (CDC13) 7.3 (m, 4), 7. 0 (t, 2), 6.9 (dd, 2), 4.7 (d, 2), 3.8-3.3 (m, 11), 2.6 (m, 2), 2.2 (m, 1), 1.8 (m, 2) ppm; 4- (4-fluorobenzyl) -1- (2- (4-chlorophenoxy) ethyl) piperazin-2-one; NMR (CDC13) 7.3 (m, 4), 7.0 (t, 2), 6.8 (d, 2), 4.2 (t, 2), 3.8 (t, 2), 3.5 (m, 4), 3.2 (s, 2), 2.6 (t, 2) ppm; 4- (4-fluorobenzyl) -1- (2- (4-chlorophenoxy) ethyl) -3- ((ethoxycarbonyl) methyl) piperazin-2-one, hydrochloride salt; NMR ICDCI3) 7.2 (m, 2), 7.1 (m, 4), 6.8 (d, 2), 4.2 (m, 9), 3.5 (m, 5), 2.9 (br s, 1), 1.3 (t, 3) ppm; (rans) - 1- ((4-chloro-2-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 2), 7.0-6.8 (m, 5), 4. 7 (br m, 2.5), 4.2 (br s, 0.5), 3.8 (s, 3), 3.6-3.2 (m, 4), 3.0 (br s, 1), 2.7 (m, 1), 2. 2 (d, 1), 1.2 (br m, 3), 1.9 (br m, 3) ppm; and zir.s) -1- ((5-Cioro-2-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 2), 7.0-6.8 (m, 5), 4.7 (br m, 2.5), 4.2 (br s, 0.5), 3.8 (s, 3), 3.6-3.2 (m, 4), 3.0 (br s, 1), 2.7 (m, 1), 2.2 (d, 1), 1.2 (br m, 3), 1.9 (br m, 3) ppm. EXAMPLE 8 Compounds of formula (la) A. To a solution of 4-chlorobenzylisocyanate (0.59 g, 3.5 mmol) in anhydrous THF (15 mL) at 0 ° C was added l- (4-chlorobenzyl) piperazine ( 0.74 g, 3.5 mmol). The resulting mixture was stirred at room temperature. After 20 hours the mixture was concentrated in volatiles. The resulting solid was washed with ethyl acetate and dried under vacuum to give 0.72 g of 1- (((4-chlorobenzyl) amino) carbonyl) -4- (4-chlorobenzyl) piperazine as a white solid; NMR (CDC13) 7.4 (m, 4), 7.3 (m, 2), 7.2 (m, 2),. 4.4-4.1 (m, 6), 3.6 (m, 4), 3.0 (m, 2) ppm. B. similarly, other compounds of formula (la) were prepared: 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (W-methylureido) amino) methyl) piperazine; NMR DCICI3) 7.2 (ir., 4), 7.0 (t, 2), 6.8 (dd, 2), 5.7 (br s, 1), 5.2 (m, 1), 5.0 μm, 1), 4.8-2.0 (m, 15) ppm; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (N '- (ethoxycarbonylmethyl) ureido) methyl) piperazine; RM? (DMSO-d e) 7.3 (m, 4), 7.1 (t, 2), 6.8 (d, 2), 6.5 (t, 2), 4.8 m, 2), 4.1-1.8 (m, 15), 1.1 (m, 3) ppm; (trans) -1- ((4-chloro-2- ((aminocarbonyl) glycineamido) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzidepiperazine; RM (CDC13) 9, 8 (br s, 1), 8.3 (s, 1), 7.3 (m, 2), 7.0 (m, 3), 6.8 (d, 1), 6.0 (br s, 1), 5.0 (m, 2), 4.8 (m, 2), 4.1 (m, 3), 3.6 (m, 3), 3.1 (m, 2), 2, 7 (d, 1), 2.3 (d, 1), 0.9 (m, 6) ppm; (trans) -1- ((4-chloro-2- ((aminocarbonyl) (methyl) glycinamide) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzylpiperazine; RM? DMSO-d) 9.8 (br m, 1), 9.4 (s, 1), 8.2 (s, 1), 7.6 (m, 2), 7.3 (m, 2), -7.0 (m, 2), 6.0 (br, 2), 5.0 (m, 3), 4.3 (br m, 3), 4.0 (s, 2), 3.7-3.2 (m, 4), 2.8 (s, 3"), 1.3 (m, 3), 1.2, 3) ppm; (trans) -l- ((4-chloro-2- (N'-ethyluredio) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; RM (CDC13) 8.8 (s, 1), S, 4 (s, 1), 7.3, 2, 7, C (m, 2), 6.8 (m, 3), 4.7 (m, * 2), 4.1 (m, 2), 3.6-3.3 (m, 4), 3. O (br s , 1), 2.7 (dd, 1), 2.2 (d, 1), 1.3 (m, 5), 0.9 (m, 6) ppm; (trans) -1- ((4 -chloro-2- (N '- (2,4-dichlorophenyl) ureido) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; RM (DMSO-de) 10, 4 (br d, 1), 9.2 (s, 1), 9.1 (s, 1), 8.2 (s, 1), 8.1 (d, 1), 7.7 (m, 2), 7.3 (m, 3), 6.9 (m, 2), 5.0 (m, 2), 4.7 (m, 1), 4.3 (m, 3), 3, 8 (q, 1), 3.6 (m, 1), 3.4 (m, 1), 2.9 (t, 1), 1.4 (m, 3), 1.2 (m, 3 ) ppm; (trans) -1- ((4-chloro-2- (N '- (4-nitrophenyl) ureido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; RM? (CDC13) 9.1 (s, 1), 8.4 (s, 1), 8.3 (s) , 1), 8.2 (s, 1), '7.9 (d, 1), 7.8 (d, 1), 7.3, m, 3), 7.0 (t, 2), 6.8 (d, 1), 6.7 (m, 1), 4.7 (m, 2), 3.6 (m, 4), 3.1 (m, 1), 2.8 (m, 1), 2.3 (d, 1) , 1.4 (m, 3), 1.0 (m, 3) -ppm; 1 trans) -1- ((4-chloro-2- (N '- (-methylphenyl) ureido) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; RM? (DMSO-dé) 10.5 (br d, 1), 9.6 (s, 1), 8.5 (d, 1), 8.2 (s, 1), 7.8 (m, 2), 7.3 (m, 4), 7. 1 (d, 2) , 6.9 (s, 1), 5.0 (m, 2), 4.3 (m, 3), 3.9 (s, 1), 3.6 (ir., 1), 3.4 (m, 1), 2.8 (dd, 1), 2.2 (s, 3), 1.4 (m, 3), 1.2 (m, 3) ppm; (trans) -1- ((4-chloro-2- (N'-benzylureido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; RM? (CDC13) 9.0 (s, 1), 8.4 (s, 1), 7.3 (m, 8), 7.0 (t, 2), 6.8 (q, 2), 5, 6 (t, 1), 4.6 (m, 4), 3.6 (m, 3), 3.0 (m, 1), 2.7 (m, 1), 2.2 (m, 2), 1. 3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- (1- (N-methyl-N'-ethylureido) ethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; RM? (CDCl 3) 7.3 (m, 4), 7.0 (t, 2), 6.8 (d, 1), 5.6 (m, 1), 5.4 (br d, 1) 4.7 (m, 2), 3.5 (q) , 2), 3.2 (m, 4), 3.0 (m, 1), 2.7 (m, 4), 2.2 (d, 1), 1.4 (d, 3), 1 , 3 (m, 9), 0.9 (m, 3) ppm; (zrans) -1- ((4-chloro-2- (oxazcl-2-ylaminomethyl) phenoxy) methyl) carbonii-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; RM? (CDCl 3) 7.3 (m, 3), 7.2 (dd, 1), 7.0 ít, 2), 6.8 (d, 1),, 7 (m, 3), 4.4 (s, 2), 4.3 (t, 2), 3.9, m, 1), 3.8 (t, 2), 3.5 (q, 2), 3.3 (m, 1), 3. 0 (m, 1), 2.7 (dd, 1), 2.2 (d, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- (2- (4-Cyorophenyl) -3- (ureido) propyl) carbonyl- benzyl) piperazine; RM? (DMSO-de) 7.3 (m, 4), 7.2 (m, 2), 7.1 (t, 2), 5.8 (br s, 1), 5.4 (br s, 2 ), 4.0 (m, 1), 3.4 (m, 2), 3.2 (m, 3), 2.9 (m, 1), 2.5 (m, 2), 2.1 (m, 1), 1.1 (m, 3), 0.8 (m, 3) ppm; (trans) -1- (2- (4-chlorophenyl) -2- (ureido) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-de) 7.3 (m, 5), 7.1 (L, 2), 6.6 (q, 1), 5.6 ibbr, 2), 5.0 (m, 1) , 4.4 (m, 0.5), 4.0 (m, 0.5), 3.5 (m, 2), 3.3 (m, 2), 2. 8 (m, 2), 2.7 (m, 1), '2.5 (m, 1), 2.1 (d, 1), 1.2 (m, 3), 0.8 (m, 3) ppm; (trans) -1- ((4-chloro-2- ((N '- (3-methoxyphenyl) ureido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO) -d6) 10.2 (br s, 1), 9.5 (s, 1), 8.5 (br s, 1), 8.2 (s, 1), 7.7 (m, 2), 7.2 (m, 4), 7.0 (s, 3), 6.5 (dd, 1), 5.0 (m, 2), 4.3 (m, 3), 3.7 (m, 5), 3.4 (m, 1), 2.9 (m, 1), 1.4 (s, 3), 1, 2 (s, 3) ppm; and (trans) -1- ((4-chloro-2- ((N '- (trichloromethylcarbonyl) ureido) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzDpiperazine; NMR (CDC1) 10, 5 (s, 1), 9.0 (m, 1), 8.3 (s, 1), 7.3 (m, 2), 7.0 (m, 4), 4.8 m, 3), 4.2 (m, 1), 3.6 (m, 2), 3.4 (m, 1), 3.01, 1), 2.7 (dd, 1), 2.2 (d, 1), 1.3 (m, 3), 0.9 (m, 3) ppm. EXAMPLE 9 Compounds of formula (la) A. To a solution of (cis) -1- ((4-chlorophenoxy) methyl) carbonyl-3,5-dimethylpiperazine (0.20 g, 0.71 mmol) in THF anhydrous (2 mL) was added 4-fluorobenzylbromide of (0.11 mL, 0.85 mmol), diisopropylethylamine (0.15 mL,, 85 mmol) and sodium iodide (0.042 g, 0.28 mmol). The resulting mixture was stirred at room temperature for 2 days. At that time the mixture was poured into ether and washed with 5% aqueous solution of NaHCO 3, then brine. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo to give a yellow oil. Purification by silica gel column chromatography gave 0, -17 g of (cis) -l - ((4-chlorophenoxy) methyl) carbonyl-3,5-dimethyl-4- (4-fluorobenzene) ) Piperazine as a rose oil; which became its hydrochloride salt; NMR (CDC13) 7.6 (m, 2), 7.3 (m, 4), 7.0-6.8 (m, 2), 5.0-2.8, 10, 1.5) -1.3 (m, 6) ppm. B. similarly, the following compounds of formula (la) were prepared: 1- ((-chlorophenoxymethyl) carbonyl-2- (((cyclopropyl) methyl) amino) methyl) -4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 4), 7.0 (t, 2), 6.8 (d, 2), 4.5 (s, 2), 3.4 (m, 4), 3 , 0 (m, 1), 2.5 (m, 4), 2.2 (t, 1), 2.0 (m, 2), 16 (s, 2), 0.8 (m 1) , 0. 5 (m, 2), 0.1 (m, 2) ppm; (31? 51?) -4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3,5-dimethylpiperazine, hydrochloride salt; NMR (CDCl 3) 13.3 (m, l), 7.9 (q, .2), 7.2 (m, 4), 6.9 (d, 2), 6.8 (d, 2), 4.8-3.3 (m, 10), 1.7 (d, 3), 1.2-1.0 (m, 3) ppm; (3S, 55) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3,5-dimethylpiperazine, hydrochloride salt; NMR (CDCl 3) 13.3 (m, l), 7.9 (q, 2), 7.2 (m, 4), 6.9 (d, 2), 6.8 (d, 2), 4 , 8-3.3 (m, 10), 1.7 (d, 3), 1.2-1. 0 (m, 3) ppm; 1- . {; ' chlorophenoxy) methyl) carbonyl-2- ((4-fluorobenzyl) amino) methyl) -4- (4-fiuorobenzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-2- (((methyl) amino) methyl) -4- (4-fluorobenzyl) piperazine: NMR ICDCI3) 7.3 (m, 4), f, 0 't, 2), 6.8 (d, 2), 4.5 (q,' 2), 3.6 (m, 4), 3, 1 (m, 2), 2.8 (m, 3), 2.6 (s, 3), 2.5-2. 3 (m, 3) ppm; and - ((4-chlorophenoxy) methyl) carbonyl-3-trifluoromethyl-4- (4-fluorocarboxyzepide); NMR "; CDC1 3) '7.3 (m, 4), 7.0" (t, 2), 6.8 (dd, 2), 4.6 (m, 2), 4.2 (m, 1), 3.8 (m, 3), 3.6 (dd, 1), 3, 3 (m, 2), 3.0 (m, 1), 2.6 (m, 1) ppm. EXAMPLE 10 Compounds of Formula (Ia) A. To a solution of 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-2- (methoxycarbonyl) methyl-4- (4-fluorobenzyl) piperazine (0, 20 g, 0.42 mmol) in a methanol / water solution (20 mL, 3: 1) was added lithium hydroxide, monohydrate (0.40 mL, 9.5 mmol). at room temperature for 30 min At that time the HPLC analysis showed that the complete conversion had taken place The mixture was poured into ethyl acetate and washed consecutively with an aqueous acetic acid / water solution (pH < 4) , water, and brine The organic layer was separated, dried over MgSO4, filtered and concentrated in vacuo to give 0.060 g of l- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-2- (carboxy) methyl-4- (4-fluorobenzyl) piperazine as a white solid; NMR (CDCl 3) 7.4 (m, 2), 7.1 (, 2), 6.2 (m, 2), 5.1 ( m, 1), 4.7 ym, 3), 4.0 (m, 2), 3. 8 (d, 9), 3.3-3.1 (m, 4), 2.6 (m, 2), 2.4 (m, 2) ppm, MS (ESI) 47 6. In a similar manner, the following compounds of the invention were prepared: 1- ((4-chlorophenoxy) methyl) carbonyl-3- (carboxy) methyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d 6) 7.4 (t, 2), 7. 3 (d, 2), 7.1 (t, 2), 6.9 (d, 2), 4.7 (m, 2), 4.0. (d, 2), 3.7 (m, 2), 3.5 (m, 3), 3.2 (m, 1), 2.8-2.4 (m, 3) ppm; 1- ((4-chloro-2-carboxyphenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 8.0 (s, 1), 7.4 (dd, 1), 7.3 (m, 3), 7.0 (t, 1), 6.9 (d, 1), 5.0 m, 2), 4.6 (m, 1), 4.3 (m, 1). 3.7 (m, 1), 3.4 (m, 2), 2.8 (d, 1), 2.6 (m, 1), 2.1 (m, 1), 1. 4 (d, 1.5), 1.3 (d, 1.5) ppm; and (trans) -1- ((4-chloro-2-carboxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 9.4 (br s, 1: .- 8, 0 (m, 1), 7, 5 (m, 3), 7. 2 (m, 2), 7.0 (d, 1), 5.0 (m, 2), 4.6 (m, 1), 4.3 (m, 3), 3.7 im, 2), 3.4 (m, 1), 3.3 (m, 1), 1.4-1.3 (m, 6) ppm. EXAMPLE 11 Compounds of formula (la) A. To a solution of lithium aluminum hydride (0.29 g, 7 mmol) in an anhydrous THF solution (16 mL) was added 1 - . 1 - »-, phenoxy; meril; carbor.il- - (4-fluorobenzyl) piperazine (0.36 g, 1.0 mmol, in 3 mL of THF). The resulting mixture was stirred at room temperature for 9 hours. At that time, 0.3 mL of water and 0.3 mL of 15% aqueous NaOH solution were added and the resulting mixture was stirred at room temperature. After 18 hours, the mixture was filtered through a short column of Celite (THF) and the filtrate was concentrated in vacuo to give 0.12 g of l- (2- (4-chlorophenoxy) ethyl) -4- (4-fluorobenzyl) piperazine as a limpid oil; NMR (CDC13) 7.2 (m, 4), 7.0 (m, 2), 6.8 (m, 2), 4.0 (m, 2), 3.4 (m, 2), 2 , 8-2.4 (m, 10) ppm. similarly, the following compounds of formula (la) or (Ib) were prepared: 5-chloro-2- [2- [(21? 55) -4- [(4-fluorophenyl) methyl] -2.5 -dimethylpiperazyl-2-oxoethoxy] benzoic acid; "" "H NMR (400 MHz, DMSO-df): .d / ppm = 0.84-0.98 (m, 3H), 1.16- 1.28 (m, 3H), 2.16 (m , 1H), 2.70 (m, 1H), 2.88 (m, 1H), 3.08 (m, 0.5H;, 3.40, 1.5H), 3.58 (m, 1 , 5H), 4.0 (m, ÍH), 4.4C, 0.5H), 4.94 (m, 1.5H), 5.18 (m, 0.5H), 7.12 (m , 3H), 7.36, m, 2H), 7.54 (m, IH), 7.62 (s, IH) 5-bromo-2- [2- [(2R, 5S) -4- [( 4-fluorophenyl) methyl] -2,5-dime-ylp-ciprazipyl] -2-cxoetcxy] -benzeneacetic acid; 1 H NMR (400 MHz, CDC13): .d / ppm = 1.00 (m, 3H), 1.30 (m , 3H), 2.05 (d, ÍH), 2.68 (dd, ÍH), 2.80 (m, ÍH), 3.05 (m, ÍH), 3.25 (m, ÍH), 3 , 60 (m, 4H), 4.10 (m, ÍH), 4.65 (m, 2H), 6.78 (m, 1H), 7.00 (t, 2H), 7.33 (m, 4H). 5-Bromo-2- [2- [(2J?) -4- [(4-fluorophenyl) methyl] -2-methylpiperazinyl] -2-oxoethoxy] benzeneacetic acid; 1 H NMR (400 MHz, CDC13): .d / ppm = 1.30 (m, 3H), 2.05 (m, HH), 2.20 (m, HH), 2.65 (d, 1H), 2.85 (m, 1H), 3.50 (m, 4H), 3.65 (m, 2H), 4.35 (m, 1H), 4.70 (m, 2H), 6.72 (d, 1H), 7.00 (t , 2H), 7.30 (m, 4H) .5-bromo-2- [2- [(21? 55) acid. -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzoic acid; 1 H NMR (400 MHz, DMSO-d 6): .d / ppm = 0.80-0.98 (m, 3H), 1.16- 1.28 fm, 3H), 2, -15 (m, 1H) , 2.55 (m, 0.5H), 2.70 (m, 0.5H), 2.95 (m, 1H), 3.08 (m, 0.5H), 3.40 (m, 1 , 5H), 3.58 (m, 1.5H), 4.00 (m, 1H), 4.40 (s, 0.5H), 4.94, 1.5H), 5.18 (m , 0.5H), 7.12 (m, 3H), 7.36 (m, 2H), 7.64 (m, ÍH), 7.74 (s, ÍH). acid-5-bromo-2- [2- [(21?, 55) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] -4-methoxybenzoic acid;: H NMR (400 MHz , CDC13):. d / ppm = 0.84-0.96 μm, 3HJ, 1.16-1.28 (m, 3H), 2.16 (m, HH), 2.70 (m, HH), 3.08 ( m, 2H), 3.50 (m, 2H), 3.72 (m, ÍH), 3.92 (s, 3H), 4.20 (s, 0.5H), 4.94 (m, 2) , 5H), 6.54 (s, 1H), 7.00 (m, 2H), 7.34 (m, 2H), 8.24 (s, ÍH). 5-chloro-2- [2- [. { 21 ?, 55) -4- [(4-f luorofenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] -4-methoxybenzoic acid * H NMR (500 MHz, DMSO-ds):. d / ppm = 0.90 (m, 3H), 1.25 (ra, 3H), 2.23 (m, 1H), 2.75 (m, ÍH), 3.35 (m, 1H), 3.45 (m, ÍH), 3.62 (m, 1H), 3.77 (m, 2H), 3.95 (s, 3H), 4.30 (s, ÍH), 5.02 (m, 2H), 6.91 (s, 1H), 7.10 (m, 2H), 7, 37 (m, 2H), 7.75 (s, ÍH). 5-Chloro-2- [2- [(21? 5S) -4 - [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] -4-methylbenzoic acid ^ H NMR (400MHz, DMSO-de + D20) :. d / ppm = 0.90-1.10 (m, 3H), 1.20-1.45 (m, 3H), 2.27 (m, HH), 2.40 ís, 3H), 2.73 m, ÍH), 3.00-4.30 (m, 5H), 4.60- 5.10 (m, 3H), 6.84 ies, 1H), 7.02 (m, 2H), 7 , 30 (m, .2H), 7.98 (s, ÍH); 4,5-dichloro-2- [2- [(21? 55) -4- [(4-fluoro-phenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzoic acid; H NMR (400 MHz, DMSO-d, 120 ° C):. d / ppm = 0.94 (d, 3H), 1.24 (d, 3H), 2.25 (d, ÍH), 2.75 (dd, ÍH), 2.95-3.00 (m, 1H), 3.34 (d, ÍH), 3.47 (d, ÍH), 3.61 Id, 1H), 3.73 (d, 1H1, 4.24-4.30 (m, 1H), 4.94 (d, ÍH), 5.03 (d, ÍH), 7.09 (dd, 2H), 7.37 (dd, 2H.), 7.41 (s, 1H), 7.81 (d. s, H) 5-chloro-2- [2- [(21? 55) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] -4- (trifluoromethyl) ) benzoic, 1 H NMR (400 MHz, CDC13): .d / ppm = 1.00 (m, 3H), 1.30 (m, 3H), 2.30 (m, HH), 2.70 (m, ÍH), 3.10 (m, 1H), 3.25 (m, ÍH), 3.60 (m, 2H), 3.70 (m, 1H), 4.65 (m, ÍH), 5, 00 (m, 2H), 7.00 (t, 2H), 7.30 (m, 3H), 8.05 (s, ÍH), 5-chloro-2- [2- [(21? ) -2,5-diethyl-4- [(-fluorophenyl) methyl] piperazinyl] -2-oxoethoxy] benzoic acid; 1 H NMR (500 MHz, DMSO-de, 120 ° C): .dbd / ppm = 0, 62 (t-rotamer, 1.25H), 0.73 (t-rotamer, 3.5H), 0.86 (t-rotamer, 1.25H), 1.24 (m, 1H), 1.37 ( m, 1H), 1.54 (m, 1K), 1.69 μm, HH), 1.84 μm, 1H), 2.26 (t, HH), 2.57 (d, 1H), 2.66 (dd, 1H), 2.90 (dd, 1H), 3.52 (m, 3H), 4.20 (d, 1H), 4.99 (m-rotamers, 2H), 7.09 (m, 3H), 7.35 (t, 2H), 7.55 (dd, 1H), 7.63 (d, 1H), 13.12 (br, 1H); 5-bromo-2- [2- [(21? 55) -2,5-diethyl-4- [(4-fluoro-phenyl) methyl] piperazinyl] -2-oxoethoxy] -4-methoxybenzoic acid; lti NMR (500 MHz, DMSO-dg):. d / ppm = CeO, m, 6H > , 1.25 (m, 0.5.4-, 1.40 (m, 1H), 1.70 (m, 4H), 1.94 (m, 1H), 3.08 (m, 4H), 3, 90 (m, 3.5H), 4.20 (br, HH), 4.90 (m, HH), 5.10 (m, 1H), 6.80 (m, 1H), 7.20 (m , 2H), 7.54 (m, 2H), 7.90 (s, ÍH), 5-chloro-4-ethoxy-2- [2- [(21? 5S) -4- [(4- fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzoic acid, 4-amino-5-chloro-2- [2- [(21? 55) -A- [(4-fluorophe- nyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzoic acid 5-chloro-2- [2- [(21? 55) -5-ethyl-4- [(4-fluo-phenyl)] Methyl] -2-methylpiperazinyl] -2-oxoethoxy] benzoic acid 5-chloro-2- [2- [(21? 5S) -5-ethyl-4- [(4-fluorophenyl) methyl] -2-methylpiperazinyl] -2-oxoethoxy] -4-methoxybenzoic acid, 5-chloro-2- [2- [(21? 55) -2,5-diethyl-4- [(4-fluorophenyl) methyl] piperazinyl] ] -2-oxoethoxy] -4-methoxybenzoic acid, 4-chloro-2- [2- [(21? 55) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy ] benzoic acid 2- [2- [(21? 55) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] -5-methylbenzoic acid; EXAMPLE 12 Compounds of Formula (Ib) A. a solution of 1- 1-, r-butoxycarbonyl) amino-2- (4-chlorophenyl) ethyl) carbonyl-4- (benzyl) piperazine (0.20 g, 0, 44 mmol) in a solution of CH 2 Cl 12 (3 mL) was added trifluoroacetic acid (3 mL). The resulting mixture was stirred at room temperature. After 18 hours, the mixture was concentrated in vacuo to give a yellow oil. This was dissolved in ethyl acetate and washed with an aqueous solution of NaKCC 3. The organic layer was separated, dried over MgSO 4, filtered and concentrated in vacuo to give 0.17 g of a clear, colorless film. This was dissolved in ether and treated with a solution of HCl in ether, resulting in the formation of a white precipitate. The concentration gave 0.18 g of 1- l-amino-2- (4-chlorophenyl) ethyl) carbonyl-4-benzyl) piperazine as a white solid; NMR (CDCl 3) ", m, 1), 7.1 μm, 2), 4.0 (t, i), 3.7-3.1 (m, 4), 2.8 μm, 2), 2 , 4-2.2 (m, 5), 1.8 (m, 1) ppm B. In a similar manner, the following compounds of formula (Ib) were prepared: 1- (3-amino-2- (4 -chlorophenyl) propyl) carbonyl-4- (4-chlorobenzyl) piperazine; NMR (CDC13; 7. 2 (m, 8), 3.8 (s, 3), 3.6-3.3 (m, 6, 3.0 (m, 2), 2.6 (dq, 2), 2.4- 2.1 (m, 4) ppm, and 1 - (l-arr.rno-2- (4-cycofenii) ethyl) carbonyl- - (4-chlorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 6), 7.1 (d, 2) , 4.0 (t, 1), 3.6-3.1 (m, 6), 2.8 (dq, 2), 2.6 (br s, 2), 2.4 (m, 3) 1.8 (m, 1) ppm C. In a similar manner, the following compounds of formula (la) were prepared: (trans) -1- ((4-chloro-2- (aminomethyl) phenoxy) - useful) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 7. 3 (m, 3), 7.2 (dd, 1), 7.0 (t, 2) , 6.8 (br d, 1), 4.7 (m, 2), 3.9 (s, 2), 3. 5 (m, 3), 3.0 (br s, 1), 2, 7 (m, 1), 2.2 (m, 4), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- (glycinamide) phenoxy) methyl) carbonane-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 10.1 (s, 1), 8.5 (s, 1), 7.3 (t, 3), 7.0 (t, 3), 6.8 (d, 1), 4 , 7 (m, 3), 4.2-3. 4 (m, 5), 3. 2 (m, 1), 3.0 (br s, 1), 2.7 (dd, 1), 2.2 (d, 1), 1. 3 (m, 3), 0.9 (m, 3) ppm; (21 ?, 55) -1- ((4-chloro-2- (glycinamide) phenoxy) methyl) carbonane-2,5-dimethyl-4- (-fluorobenzyl) piperazine; NMR (DMSO-d 6) 10.0 (s, 1), 8.2 (m, 3), 7.6 (s, 1), 7.3 (m, 2), 7.1 (dd, 1), 6.9 ym, 1), 5.2-4.2 (m, 5), 3.8-2.9 (m, 7), 1.2 (m, 6) ppm; (21?) -1-. { (4-parrot-2- fgi i cinarrade) fenexi) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 11. 4 (br s, 1), 10.0 (s, 1), 8.3 (br s, 2), 8.1 (s, 1), 7.8 (m, 2), 7.4 (t, 2), 7.1 (d, 1), 7.0 (d, 1) 5.0 (q, 2), 4.7 (m, 1), 4.3 (m, 3), 3.9 (m, 3), 3.6 (m, 1), 3.1 (m, 3), 1.5 (d, 1.5), 1.3 (d, 1.5) ppm; (trans) -1- ((4-chloro-2- ((N '-methylglycinamido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; RM (CDC13); , 9 ís, 1), 8.5 (s, 1), 7.3 (m, 3), 7.0 (m, 3), 6.8 (d, 1), 4.7 (m, 3 ), 4.2-3.9 (m, 1), 3.6-3.3 (m, 5), 3.0 (br s, 1), 2.7 (dd, 1), 2. 5 (s, 3), 2.3 (d, 1), 1.3 (m, 3), 1.0 (m, 3) ppm; (trans) -1- ((4-chloro-2- (alaninamido) phenoxy) methyl) carbonyl-2,5-dimethyl-1-4- (4-fluorobenzyl) piperazine; RM? (CDCI3) 10. 2 (s, 1), 8.5 (s, 1), 7.3 (m, 3), 7.0 m, 3), 6.8 (d, 1), 4.7 fm, 3), 4.2- 3.9 (m, 1), 3.6-3.2 (m, 5), 3.0 (m, 1), 2.7 (dd, 1), 2 , 2 (d, 1), 1.4 (d, 3), 1.3 (m, 3), 1.0 (br s, 3) ppm; (zrans) -1- ((4-chloro-2- (1- (methylamino) ethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; RM? (CDCl 3) 7.3 (m, 3), 7.1 (dd, 1), 7.0 (t, 2), 6.8. { br d, 1), 4.7 (m, 3), 4.0 (q, 2), 3.6: q, 2), 3. 2 (m, 1), 3.0 (m, 1) , 2.7 (dd, 1), 2.3 (m, 4), 1.3 (m, 6), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- ((methylamino) (phenyl) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.6 (br d, 1), 74-7.1 (m, 8), 7.0 (t, 2), 6.8 (m, 1), 5.0 (d, 1 ), 4.6 (m, 3), 4.2 (m, 1), 3.5 (t, 1), 3.4-3.0 (m, 4), 2. 8 (m, 1), 24 (s, 3), 2.2 (m, 1), 1.2 (m, 3), 0.8 (m, 3) ppm; (21?) -1- ((4-chloro-2- ((piperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d 6) 9.2 (br s, 1), 7.6 (m, 4), 7.3 (t, 2), 7.2 (d, 1), 5.2 (dd, 1), 5. 0 (d, 1), 4.8 (m, 1), 4.4 (d, 4), 3.9 (d , 1), 3.4 (m, 11), 1.4 (d, 1.5), 1. 2 (d, 1.5) ppm; (21? 55) -1- ((4-Chloro-2- (piperazin-1-methyl) -hexyl) methyl) carbonyl-2, 5-dimethyl-4- (4'-fluorobenzyl) pipera? Ina NMR (DMSO-d6) 9.8 (br s, .1), 9.2 (br s, 1), 7.6 (s, 3), 7.5 { Dd, 1), 7, 3 (t, 2), '7.2 (d, 1), 5.4 (m, 1), 5.0 (m, 3), 4.7 (m, l), - 4.5 (s) , 2), 4.3 (m, 3), 3.7-3.1 (m, 11), 1.4-1. 1 (m, 6) ppm;,. { trans) -1- ((4-chloro-2-. {(piperazin-1-yl) methyl) phenoxy) methyl) carbonii-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 11.3 (br d, 1), 9.7 (m, 2), 7.9 (m, 2), 7.7 (m, 2), 7.- 4-7, 2 (m, 3), 5.4 (m, 1), 5.0 (m, 2), 4.6 (m, 1), 4.2 (m, 3), 3.8-3.2 (m, 10), 2.8 (dd, 1), 1.7 (m, 3), 1.4 (dd, 3), 1.2 (m, 3) ppm; (trans) -1- (2- (4-chlorophenyl) -3- (amino) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 4), 7. 2 (d, 2), 7.0 (t, 2), 4.8 (m, 1), 4.2 (m, 1), 3 , 9 (ra, 1), 3.5-3.2 (m, 3), 2. 9 (m, 3), 2.6 (m, 2), 2.2 (m, 1), 1, 2 (m, 3), 0.8 (m, 3) ppm; and (trans) -1- (2- (4-chlorophenyl) -2- (amino) ethyl) carbonyl-2,5- dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 7. 3 (m, 6), 7.0 (t, 2), 4.7 (m, 0.5), 4.5 (m, 1), 4.2 (d, 0, 5), 3.5 (q, 2), 3. 2 (m, 1), 3.0 (m, 1), 2.6 (m, 2), 2.5 m, 2, 2.2 ( m, 1), 1.2 (m, 3), 0. 9 (m, 3) ppm. EXAMPLE 13 Compounds of Formula (Ia) A. To a solution of. { Rr.s' - 1- ((4-Chloro-2-carboxy-noxymethyl) carbonyl-2,5-d? methyl-4-? - fluorobenzyl) piperazine (0.217 g, 0.50 mmol) in a tetrahydrofuran solution (5 mL) at 0 ° C, SOCIO LÍIO chloroformate (0.075 g, C, 55 mmcl, and? / '- methylmorpholine (0.0556 g, 0.55 mmol) was added.The resulting mixture was stirred at 0 ° C. for 20 min, resulting in the formation of a white precipitate, then a solution of methylamine in tetrahydrofuran (0.25 mL, 2.0 M, 0.50 mmol) was added and the mixture was stirred for a further 30 min. in which the volatiles were concentrated in vacuo The resulting solid was dissolved in ethyl acetate and washed with water, then brine, dried over MgSO, filtered and concentrated to 0.208 g of a foam, which was dissolved in acetate of ethyl ether and treated with a 1 M solution of HCl in ether (excess) The resulting solid was collected by filtration and washed with ethyl acetate.Dry drying gave 0.19 g of (trans) -1- ( (4-chloro-2- im tilaminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4-í 4-fluorobenzyl) piperazine as a white solid; NMR (DMSO-de) 10.8 (br d, 1), 9.2 (br s, 1), 7.8 (s, 2), 7.7 (m, 1), 7.6 (m, 1), 7.3 (m, 3), 5.4 (d, 1), 5.0 (m, 2), 4.7 (m, 1), 4.3, 3), 4.0 (m, 1), 3.6 (m, 2), 2. 8 (s, 3), 1.4 (m, 3), 1.3 (m, 3) ppm. B. In a similar manner, the following compounds of formula (la) were prepared: (trans) -1- ((4-chloro-2- ((aminocarbonylmethyl) aminocarbonyl) phenoxy) -methylcarbony-2, 5-dimethy1- 4- (4- fluorobenzyl) piperazine; NMR (DMSO-d6) 9.4 (br s, 1), 7.8 (s, 1), 7.6 (dd, 1), 7.4 (m, 2 ), 7.2 (d, 1), 7.1 (t, 2), 7.0 (s, 1), 5.3 (m, 1), 5.0 (m, 2), 4.4 (m, 1), 4.0 (m, 1), 3.8 (d, 2), 3.5 (m, 2), 3.0 (m, 1), 2.7 (m, 1) , 2.2 (br d, 1), 1,2 (br d, 3), 0.9 ibr d, 3) ppm; (trans) -1- ((4-chloro-2- ((2-aminoethyl) aminocarbonii) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 9.4 (br s, 1), 8.2 (s, '1), 7.3 (m, 3), 7.0 (t, 2), 6.8 (d, 1) , 4.7 (m, 3), 4. 2 (m, 1) 3.6 (m, 5), 3.1 (m, 3), 2.7 (br d, 1), 2. 3 (d, 1), 1.3 (br d, 3), 1.0 (m, 2) ppm; (trans) -1- ((4-chloro-2- ((4-aminocarbonylphenyl) aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d 6) 11.4 (s, 1), 7.9 (m, 5), 7.7 (d, 1), 7.4 (m, 3), 7.1 (t, 2), . 4 (d, 1), 5.1 (m, 2), 4.6 (br s, 1), 4.0 (m, 1), 3. 5 . { m, 3), 3. 0 (m, 1), 2.2 (m, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; and (trans) -l- (2- (4-chlorophenyl) -3- (t-butoxycarbonylamino) propyl) carbonyl-2,5-dimethyl-4-. { 4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 4), 7.2 (d, 2), 7.0 (t, 2), 4.8 sbr, 1;, 4.6 (m, 1), 4 , 0 (m, 1), 3.4 (m, 6), 3", O (m, 1), 2.6 (m, 2), 2.1 (m, 1), 1.4 (s) , 9), 1.2 (m, 3), 0.9 (m, 3) ppm EXAMPLE 14 Compounds of formula (la) A. To a solution of hydroxylamine hydrochloride, (0.17 g, 2.5 mmol) in DMSO (3 mL) was added triethylamine (0.252 g, 2.5 mmol) The mixture was stirred at room temperature for 10 minutes, then filtered and washed with THF.The filtrate was concentrated in vacuo to remove the THF was then treated with (trans) -1- ((4-chloro-2-cyanophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine (0.200 g, 0.48 mmol). The resulting mixture was heated at 75 ° C for 20 hours, at which time the mixture was diluted with water and extracted with ethyl acetate.The organic extract was washed with water, then brine, dried over MgSO4, filtered, concentrated vacuum to give 0.21 g of an oil, 0.030 g of this oil was dissolved in ethyl acetate and treated with i M solution of HCl in ether (excess). The resulting solid was collected by filtration and washed with ethyl acetate. Vacuum drying gave 0.027 g of (trans) -l- ((4-chloro-2- (hydroxyamidino) phenoxy) methyl) carbonyl-2,5-imeti-4-4"-4-trifluorobenzyl) pipera? ina as a white solid; NMR (CDC13) 7.6 (s, 1), 7.3 (t, 2), 7.2 (dd, 1), 7.0 (t, 2), 6.7 (br d, 1), 6.1 (br s, 2), 4.7 (m, 3), 3.7 (br d, 1), 3. 5 (q, 2), 3.2 (m, 1), 3.0 (m, 1), 2.7 (m, 1), 2.2 (t, 1), 1.3 (m, 3), 0.9 (m, 3) ppm. EXAMPLE 15 Compounds of Formula (Ia) A. To a solution of 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (2-hydroxyethyl) piperazine (0.134 g, 0.33 mmol ) and triphenylphosphine (0.100 g) in THF (6 mL) at 0 ° C were added diethyl azodicarboxylate (0.060 mL) and diphenylphosphorylazide (0.081 mL). The mixture was stirred at room temperature for 2 days, then concentrated in volatiles in vacuo. Purification by column chromatography on silica gel gave 0.047 g of l - ((4-chlorophenoxy) methyl) carbonyl-2- (2-azidoethyl) -A- (4-fluorobenzyl) piperazine as a clear, colorless oil.; NMR (CDCl,) 7.3 μm, 4), 7.0 (t, 2), 6.9 (d, 2), 4.7 (m, 3), 4.4 (br d, 1), 4.3 (m, 1), 4.1 (m, 1), 3.5-3.1 (m, 4), 2.8 (d, 1), 2.7 (d, 1), 2 , 1 (m, 2), 1.8 (m, 1) ppm. EXAMPLE 16 Cc.Tp.This of Formula (la) A. To a solution of (trans) -1- ((4-chloro-2-aminophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) ) piperazine (0.169 g, 0.416 mol) in 10 mL of methylene chloride was added phthalic anhydride (0.074 g, 0.499 mol) and several molecular sieves of 4Á. The mixture was stirred at room temperature for 3 hours, then at 70 ° C for 3 hours. At this time the mixture was cooled to 0 ° C and treated with oxalyl chloride (0.064 g, 0.499 mol). This was stirred at room temperature for 3 hours then partitioned between methylene chloride and water. The organic layer was concentrated to give an oil. Purification by column chromatography on silica gel gave 0.058 g of a clear oil. This was dissolved in ethyl acetate and treated with ITM solution of HCl in ether (excess). The resulting solid was collected by filtration and washed with ethyl acetate. Drying under vacuum gave -0.045 g of (trans) -1- ((4-chloro-2- (phthalimido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine as a solid White; NMR (CDC13) 7.9 (m, 2), 7.8 (m, 2), 7.4 (d, 1), 7.3 (m, 3), 7.05 (d, 1), 7 , 0 (t, 2), 4.6 μm, 3), 4.0 (m, 1), 3.5 (m, 1), 3.4 (m, 2), 2.9 (m, 1 ), 2.6 (m, 1), 2.2 (m, 1), 1.2 (m, 3), 0.9 (m, 3) ppm.

B. similarly, the following compound of formula (la) was prepared: (trans) -1- ((4-chloro-2- (maleimido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC1) 7.3 (m, 6), 7.0 (t, 2), 6.8 (s, 1), 4.6 (m, 3), 4.0 (m, 1), 3.5 (q, 2), 3.2 (m, 1), 3.0 (br s, 1), 2.6 (dd, 1), 2 , 2 (br d, 1), 1.2 (m, 3), 0.9 (m, 3) ppm. EXAMPLE 17 This example illustrates the preparation of representative pharmaceutical compositions for oral administration containing a compound of the invention, or a pharmaceutically acceptable salt thereof, for example, l - ((2-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine hydrochloride salt: A. Ingredients% w / w Compound of the invention 20.0% Lactose 79.5% Magnesium stearate 0.5% The above ingredients are mixed and dispensed in hard shell gelatin capsules containing 100 mg each, one capsule contains approximately one total daily dose.

B. Ingredients% w / w Compound of the invention 20.0% Magnesium stearate 0.9% Starch 8, 6% Lactose 69.6% PVP (polyvinylpyrrolidine) 0.9% The above ingredients with the exception of magnesium stearate they are combined and granulated using water as granulation liquid. The formulation is then dried, mixed with the magnesium stearate and formed into tablets with an appropriate tabletting machine. C. Ingredients Compound of the invention 0.1 g Propylene glycol 20.0 g Polyethylene glycol 400 20.0 g Polysorbate 80 1.0 g Water q.s. 100 mL The compound of the invention is dissolved in Propylene glycol, Polyethylene glycol 400 and Polysorbate 80. A sufficient amount of water is then added with stirring to give 100 mL of the solution which is filtered and packed. D. Ingredients% w / w Compound of the invention 20.0% Peanut oil 78. 0% Span 60 2.0% The above ingredients are melted, mixed and poured into soft elastic capsules. E. Ingredients% w / w Compound of the invention 1.0% Methyl or carboxymethylcellulose 2.0% saline 0.9% q.s. 100 mL The compound of the invention was dissolved in the saline / cellulose solution, filtered and packaged for use. EXAMPLE 18 This example illustrates the preparation of a representative pharmaceutical composition for parenteral administration containing a compound of the invention, or a pharmaceutically acceptable salt thereof, for example, 4- (4-fluorobenzyl) -1- ((2- ((acetylamino) methyl) -4-chlorophenoxy) methyl) carbonyl-2,5-methylpiperazine: Ingredients Compound of the invention 0.02 g Propylene glycol 20.0 g Polyethylene glycol 400 20.0 g Polysorbate 80 1.0 g saline solution 0 , 9% qs 100 mL The compound of the invention is dissolved in Propylene glycol, Polyethylene glycol 400 and Polysorbate 80. Then a sufficient amount of 0.9% saline desolcution is added with stirring to give 100 mL of the I.V. which is filtered through a 0.2 m membrane filter and packed in sterile conditions. EXAMPLE 19 This example illustrates the preparation of a representative pharmaceutical composition in suppository form containing a compound of the invention, or a pharmaceutically acceptable salt thereof, by. Example, 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (2-hydroxyethyl) piperazine: Ingredients% w / w Compound of the invention 1.0% Polyethylene glycol 1000 74.5% Polyethylene glycol 4000 24.5% The ingredients are melted together and mixed on a steam bath, and poured into molds containing 2.5 g total weight. EXAMPLE 20 This example illustrates the preparation of a representative pharmaceutical composition for insufflation containing a compound of the invention, or an acceptable salt for pharmaceutical use thereof, for example, (21? 5J?) -4- (4- fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2,5-dimethylpiperazine: Ingredients% w / w micronized compound 1.0% micronised lactose 99.0% The ingredients are milled, mixed and packed in an insufflator equipped with a dosing pump. EXAMPLE 21 This example illustrates the preparation of a representative pharmaceutical composition in nebulized form containing a compound of the invention, or a pharmaceutically acceptable salt thereof, for example, l - (((4-chlorophenyl) amino) methyl) carbonyl-4- (4-chlorobenzyl) piperazine: Ingredients% w / w Compound of the invention 0.005% Water 89.995% Ethanol 10,000% The compound of the invention is dissolved in ethanol and mixed with water. The formulation is then filled in a nebulizer equipped with a dosing pump. EXAMPLE 22 This example illustrates the preparation of a representative pharmaceutical composition in aerosol form containing a compound of the invention, or a pharmaceutically acceptable salt thereof, eg, 1- ((4-chloro-2- ( ((ethyl) amino) methyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine: Ingredients% w / w Compound of the invention 0.10% Propellant 11/12 98.90% Oleic Acid 1.00% The compound of the invention is dispersed in oleic acid and Iso propellants. The resulting mixture is then poured into an aerosol container equipped with a metering valve. In the following examples, 293MR cells are used. They are human kidney embryonic cells (HEK293) which were stably transfected to express the human CCR1 receptor by the following pdure: HEK293 cells were obtained from the American Type Culture Reco-lesson (ATCC CRL 1573). The CCRl human cDNA was achieved thanks to the collaboration with Dr. Stefen Peiper of the University of Louisville, Kentucky. The CCR1 gene was subcloned using standard techniques (see, for example.

Molecular Cloning: A Labora toriy Manual, 2nd Edition, Cold Spring Harbor Laboratory Press, 1989) in a standard plasmid containing the SV40 promoter and enhancer. The plasmid also contained genes for resistance to hybromycin and puromycin. Standard transfection protocols with calcium phosphate were used to insert the plasmid into HEK293 cells. The cells were selected according to their stable expression of CCRl using selection with hygromycin and puromycin. The capacity of the cells to bind with high affinity RANTES or MlP-la marked with: = I was tested. EXAMPLE 23 In Vitro Test: Calcium Flow Like the CCR1 receptor, in common with seven other transmembrane receptors coupled with G protein, it responds to the binding of its ligand, for example, MlP-la and RANTES, mobilizing calcium free intracellular, biological activity can be measured by calcium flux assays using the fluorescent dye Fura 2. In the next assay, the ability of the compounds of the invention to block said biological response was measured. Protocol: 1.}. 293MR cells from two flasks were detached, washed and resuspended in Hanks Ca2 + (50ml Hanks, 1.0ml Hepes IM, 1.6ml 500mM CaCl2, pH 7.4). The cells were washed twice in said media. 2) CCR1 cells were counted = 28 x 106 cells were taken to 2 x 10 6 cells / ml by suspending them in 1 ml of Hanks Ca2 +. 3) to 10 ml of the cells (20 x 106) were added 30 ml of medium (with 50 μg of Fura in 50 μl of DMSO). The final cell concentration was 1.0 x 10 6 cells / ml. The final concentration of Fura was 1.25μM. 4) the cells were incubated at 37 ° C for 30 minutes in the presence (or absence) of increasing concentrations of the compounds of the invention. The cells were washed as just said to eliminate the free Fura. The cells were resuted at 1 x 10d cells / ml. Then an aliquot of the cells (2.0 ml) was taken in a cuvette and placed in a spectrofluorimeter. The cells were then stimulated with both MlP-la and RANTES (Peprotech Inc.) and the release of Ca "+ was measured in the spectrofluorimeter 5) The data were corrected for nM Ca2 + released by adding lOOμl of 0.1% Triton X-100 (for maximum values) followed by lOOμl of 500mM EGTA, pH 8.5 (for minimum values).

In testing the compounds of the invention in this assay, they demonstrated the ability to inhibit Ca2 + mobilization in response to binding of MlP-la and RANTES with the CCR1 receptor. EXAMPLE 26 In Vitro Test: The tests were carried out in a microphysiometer to investigate the functional activity of the antagonist of interest. The microphysiometer evaluates the cellular response through the use of a silicon-based potentiometric sensor that can measure small changes in the pH of the solution (Hafeman et al., Science (1988), Vol. 240, pp. 1182 -1185; Parce et al., Science (1989), Vol. 246, pp. 243-247). It has been shown that the microphysiometer can be used to measure metabolic rates of living cells (Parce et al., 1989). Activation of cell membrane receptors can alter the rate of extracellular acidification (Oicki et al., Proc.Na.I Acad. Sci. (1989), Vol. S "7, pp. 4007-4011). The following test demonstrates that activation of the CCR1 receptor is expressed endogenously in human THP-1 cells, physiological changes induced by MlP-la and RANTES causing increased metabolic rates and that the compounds of the invention inhibit said effect in a dose-dependent manner Materials: 1. Cytosensor capsule element set (Molecular Devices Cat. # R8013) 2. Agarose inclusion medium (Molecular Devices Cat. # R8023) 3. Modified media for RPMl cytosensor 1640, with mild pH buffering (Molecular Devices Cat. # R8023). 4. set of Sterilant elements for the cytosensor (Molecular Devices Cat. # R8017). 5. Maintenance element set for the reference electrode (Molecular Devices Cat. # '0310-2805). 6. Working solution of MlP-la or RANTES (Peprotech In .-) -: - lOμM in modified RPMl 1640 medium (Molecular Devices Cat. # R8016) supplemented with Img / ml of BSA (bovine serum albumin), 100 units / ml of penicillin, and 100μg / ml of streptomycin). Said work solution will be referred to hereinafter as "modified culture medium". 7. Working solution of MCP-1: lOμM in modified culture medium. 8. Stock solution of compounds of the invention: ImM in DMSO. { stored at room temperature). 9. cell culture: a. THP-1 (ATCC Cat. # TIB202). b. Tissue culture medium: RPMl 1640 supplemented with 10% FBS (fetal bovine serum). Said medium will be referred to hereinafter as "culture medium". Test procedure: THP-i cells were cultured in T-25cm2 flasks in culture medium at 37 ° C, 5.0% C02, 95% air to a cell density of lxl06 cells / ml. The cells were harvested by centrifugation (5 minutes at 20G) and resuspended in modified culture medium. A cell count was performed by exclusion with Trypan blue dye and the cells were found to be = 90% viable. The cells were recentrifuged, the supernatant was removed, and the obtained granule was resuspended to a final cell concentration of 1x106 / 0, lml. The cell inclusion reagent was melted in agarose and placed in a 37 ° C water bath. The cell suspension was prepared: 0.15 ml of the THP-1 cells were added to a 1.5 ml centrifuge tube with 50 μl of the melted agarose solution. Addition to the capsule containers: the capsule containers were placed in a 12 cavity microtiter plate, a separator was added to the capsule-container, and 7 μl of cell / agarose suspension was pipetted in the center of the container. After three minutes, 1ml of modified culture medium was pipetted to the outside of the capsule-container, and 200μl of modified culture medium was pipetted into the interior. The capsule insert was then placed into the container with a sterile forceps and 500μl of modified culture medium was pipetted into the insert. The filled capsules were filled in the microphysiometer chambers. The chambers were perfused at a speed of 100μl / minute with modified culture medium. The pumping cycle was 50 seconds on- and 40 seconds off. Several data points were taken to represent the metabolic rate and used as a baseline. The cells were exposed to the compounds of the invention for 30 minutes before the addition of chemokine agonists to a final concentration of lOnM. Treated and untreated cells were exposed to the agonist for 100 seconds and the data was collected. When tested in this assay, the compounds of the invention demonstrated the ability to inhibit the activation of the CCR1 receptor by MlP-la or RANTES. EXAMPLE 25 In Vitro Assay for CCR1 receptor antagonists.

This assay demonstrates the affinities of the compounds of the invention for binding to the CCR1 receptor. The binding affinities of the compounds were determined by the CCR1 receptor based on their ability to compete with 125 I-MIP-la or 125 I-RANTES for binding to the CCR1 receptor. Reagents and Solutions: MlP-la and RANTES (Peprotech Inc.) Cells: 293MR cells (KD = l-3nM and Bmax = 2-3 x 10e sites / cell) were detached by trypsinization and placed in flasks at least 48 hours before the experiment. Ligand: 1 5I-MIP-la and 125I-RANTES from New England Nuclear (specific activity of 2200Ci / mmol, 25μi / vial) in Iml of H: 0 were reconstituted. Test buffer for buffering: 130mM NaCl, 5mM KCl, MnCl2 ImM, 50mM Tris, 30μg / ml bacitracin, 0.1% BSA, pH 7.4. Washing pH buffer: Phosphate buffer (PBS) Compounds of the invention: The stock solution of the compounds was lmM in DMSO at 10C1. The highest concentration in the assay was 10 μM and could vary depending on the potency of the compounds. A 1: 3 series dilution was made from the highest concentration, with assay buffer. Usually six concentrations of each compound were analyzed to generate a dose curve from which the Ki value was determined. Test procedure: The. The tests were carried out in 96-well microtitre plates with a V bottom with a total volume of lOOμl. The 293MR cells were detached from the T225cm flasks in PBS by shaking them.The cells were washed once in PBS and resuspended in the assay buffer to approximately 1, -1 x 105 cells / ml. Cells (approximately 8000 cells / assay) were incubated both with 12I-MIP-la and with 125I-RANTES (approximately 15,000-20, OOOcpm / assay) in the presence and absence of different concentrations of the compounds at room temperature for 30 minutes. -40 minutes. The reactions were done by harvesting a GF / B filter plate soaked before with 0.3% PEI.

(Sigma # P-3143) plus 0.5% BSA and washing 5 times with cold PBS. The radioactivities in each cavity were determined by scintillation beads after adding 50μl of scintillation fluid. The non-specific binding was defined by binding in the presence of MlP-la or RANTES without labeling lOOnM. The concentration of CCR1 receptor that was used in the assay was 125I-MlP-0.4nM or 125I-RANTES 0.06nM. The concentrations of the compounds in the assay were typically between 10 μM and 30 nM at 1: 3 dilution and the concentrations for the most potent compounds were lower, depending on potency. Calculations: The dose curves of each compound were generated with 6 concentration points and the IC50 values were determined by fitting the data to the log-logit (linear) equation with an EXCEL spreadsheet. Then the K ^ values were calculated by dividing the IC5C by 1.025, to correct the concentration of labeled ligand. When the compounds of the invention were tested in this assay, they demonstrated their affinity for binding to the CCR1 receptor. The data given in Table 2 show that the compounds on the list bind to a CCR1 receptor and compete with MlP-la and RANTE ?. The K values? they are within the range between l-172nM.

Table 2 is only a selection of the compounds that were tested. Table 1 gives a comparison with other known piperazine compounds. The compounds according to the present application (No. 10-12) have higher binding affinities to the .CCR1 receptor than the alkylated compounds on carbon a (No. 1-6, 13) and the compounds that are not substituted on the Piperazine ring (No. 1-9). For example, compounds 1-6 have K values? greater than 10 μM. Example 26 The effects of a CCR-1 antagonist on cell migration / chemotaxis in human U937 cells and peritoneal macrophages, isolated from peritoneal fluid from patients with endometrosis and controls were analyzed. Chemotaxis was tested in Boyden chambers containing permeable TEM membranes (Becton Dickinson, Franklin Lakes, NJ) with a pore size of 0.4 μm polyethylene terephthalate (P.E.T.). In this assay, a human histiocytic cell line (U937) that can be induced to show monocytic differentiation and chemotactic responsiveness after treatment with cyclic 8-bromo-adenosine monophosphate (cAMPj ImM (Kay et al., 1983).

U937 cells were cultured at 37 ° C with 5% C02 in RMPI medium supplemented with 10% fetal bovine serum and penicillin G (100U / ml), streptomycin (100μg / ml) and gentamicin (50μg / ml) and incubated with 8-bromo-cAMP lmM (Sigma, St. Louis, MO) every 24 hours for a total of 48 hours. The presence of CCR-1 protein in U937 cells and peritoneal macrophages was confirmed by Western blot analysis: 50μg of protein lysates from U937 cells were subjected to SDS-PAGE and proteins were transferred to nitrocellulose paper as described in Horriung et al. 1997. Mouse IgG monoclonal antibodies were cultured against the human RANTES receptor CCR-1. A peritoneal fluid of 16 patients with moderate or severe endometrosis was prepared. The amount of RANT? S protein was measured with specific ELISAs (R & D Systems). The samples were diluted 1: 4 in PBS with 0.1% BSA and placed in the bottom of cavities of the Boyden chambers (600μl per cavity). TEM membranes of P.E.T were then fixed in 24-well plates to separate bottom and top compartments and 500,000 cells in 200μl of PBS with 0.1% BSA were added to the upper wells. Before eating the experiments, the cells were premubbed for 30 min with CCRl antagonist.

As a control, the cells were treated with PBS. The charged chambers were incubated at 37 ° C in humidified air with 5% C02 for 120 minutes. Cells that did not migrate were removed by several washes with PBS and the cells that migrated were fixed to the membrane with absolute methanol overnight at 4 ° C and stained with Crystal Violet (Sigma, St. Louis, MO). Optical absorption at a wavelength of 570 nm was used to quantify the chemotaxis of monocytes. The same mixture of peritoneal fluid was always used as a positive control and the values were normalized to 100% in each set of experiments. As a negative control, PBS was always used alone. To evaluate the inhibitory effect of the CCR-1 antagonist, the same peritoneal fluid mixture of 16 patients with moderate or severe endometrosis was used. The CCR1 antagonist was added at concentrations of 10 ~ 10, 10 ~ 9, 10 ~ 8, 10"" or 10 ~ mole. Apoptosis ELISA Cell death programmed by apoptosis was characterized by formation of genomic DNA fragments of multinucleosome size. The DNA fragments are multiples of 180bp subunits associated with histone nuclei. The levels of DNA lioeradc were measured in the cytosol of the apoptotic cells using the set of elements - detection by ELISA of cell death (Roche, Mannheim, Germany). It is a quantitative enzyme-linked sandwich immunoassay using antibodies against DNA and histones. The degree of DNA fragmentation is expressed as an enrichment factor, which is calculated by dividing the absorbance of a sample determined by the absorbance of the corresponding 10% FCS control. Evaluation of apoptosis in U937 cells treated with CCR-1 A potential mechanism of inhibition of chemotaxis is by monocyte apoptosis. To exclude said potential mechanism, the inventors used a DNA-aggregating ELISA. U937 cells were cultured for 24 h in 10% FCS and control) and 2.5%. The 2.5 * FCS sample was incubated with CCR-1 antagonist (ZK811752). Cells treated with TNF-alpha in 2.5% FCS were used as a positive control. Statistical analyzes All the experiments were repeated three times and the results were expressed as the mean ± SD. The data with normal distribution were analyzed by paired t test or A ZV. The nonparametric data were analyzed using the Kruskal-Wallis and Mann-Whitney statistics. Significant differences were accepted when the two-tailed analysis gave P <; 0.05. Example 27 Determination of CCRl mRNA in endometrial and endometriosis tissue sample by quantitative RT-PCR analysis in real time. Total RNA was extracted from the endometrium and endometriotic lesions using Trizol Reagent (Life Technologies, cat no: 15596-026). Then 20μg of total RNA was used to enrich poly (A) + RNA (Medcalf et al., EMBO J. 1986; 5, 2217). The synthesis of cDNA was performed using a Sup.erScript First-Strand synthesis system (Invitrogen). The quantification of mRNA abundance was performed by real-time PCR detection using an ABI PRISM 7700 sequence detection system (PE Biosystems, Inc., Weiterstadt, Germany) and SYBRGreen as a fluorescent dye specific for double-stranded DNA. (SYBRGreen PCR Master MIX, PE Biosystems). For the quantification of amplified transcripts, 0.2μl of cDNA of the first strand was used. The relative quantification of the AIS FRISM 7700 sequencing system data was performed using the comparative CT method. First specific pair for detection of CCR1: 5V-CTC-CGT-GCC-AGA-AGG-TGA-AC-3 'and 5 -CCA-GGA-CCA-CCA-GGA-TGT-TT-3'. The internal control and reference gene was the domestic cyclophilin gene (Primer pair: 5 '-GAA-GTT-GGC-CGC-ATG-AAG-A-3' and 5 '-GCC-TAA-AGT-TCT- CGG-CCG-T-3 '). PCR reaction: 10 min 95 ° C, 15 sec 95 ° C, 1 min 62 ° C (40 cycles). The purity of the amplification products was controlled by melting curves. Example 28 Immunohistochemical analysis of CCR1 in endometriotic lesions and in the endometrium. The biopsies were frozen at the collection point and stored at -80 ° C. To cut them, the tissues were first included in TissueTek 'Sakurai and equilibrated at -20 ° C. Prior to immunostaining, the frozen plates were thawed and air-dried for 2 hours at room temperature. For the immunohistochemical analysis, the sections of tissue were then cut using a Leica Kryotome and mended on SuperFrost Plus glass plates. The 5μm cryosections were performed and fixed for 10 min in acetone at 4 ° C. Fixed cryosections were washed in TBS and blocked with peroxidase blocking solution (DAKO). After another washing procedure, the tissue plates were blocked for 15 min with DAKO protein blocking solution. The tissue from peritoneal and endometrial lesions was incubated for 30 min with a monoclonal antibody for CCR1 (clone 53504.111, R &D Systems) with a concentration of 0.8 μg / ml. Immunohistochemical staining was carried out with DAKO EnVision System goat anti-mouse element, Peroxidase (AEC) (DAKO: K4004). The samples were washed and incubated with EnVision-Peroxidase-labeled polymer system (DAKO). After 15 min of incubation with AEC-Chromogen the samples were washed and incubated for 5 min in hematoxylin. The dyed fabrics were included in Fluoromount G (Dunn Labortechnik GmbH). For the characterization of the immune cells expressing CCR1, the samples were stained with antibodies for CD4 / CD14 and CD68 (Dako) and Alexa 568 (Molecular probes). The stained tissues were examined with an Axioplan microscope by imaging. Photographs were taken with the AxioCam camera system, Axiovision 3.1, KS400 (Cari Zeiss). All images were taken with the same exposure time. Example 29 Effects of the compounds according to the present invention on surgically induced endometrosis in intact rats that go through a cycle. Surgical procedure: Endometrosis was surgically induced in female Wistar rats (200g-250g body weight) with a normal 4-day menstrual cycle. All procedures were carried out under sterile conditions. During the first laparotomy, a 2 cm portion of the right uterine tube was resected and placed in PBS at 37 ° C. The uterine segment opened longitudinally, and the endometrium was peeled to separate it from the myometrium. A segment was transplanted to the parietal peritoneum of the right abdominal wall and the other segment to the arterial cascades of the intestinal mesentery. The segments were sutured using silk suture no. absorbable in four corners, with the surface of the endometrium towards the lumen of the peritoneal cavity. Four weeks after the induction of endometrosis, the animals underwent a second laparotomy to evaluate the size and viability of the endometrial ectopic tissue. Macroscopically, said laparotomy revealed the formation of cystic structures (foci similar to endometrosis) in -90% of the animals. The surface area was measured in length X width (mm2) using a gauge. For the experiment only animals were used where the ectopic endometrium had formed foci similar to endometrosis in both positions. "The animals were divided into 4 groups (n = 10 animals per group) .The animals of group 1 (controls) received only vehicle The animals of group 2 were treated with a antigens (positive control reference) (dose lmg / kg) daily, those in group 3 received 50mg / kg with (2R) -l- { [4-chloro-2 - (ureido) phenoxy] methyl.} carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine as the chloride salt twice a day The animals of group 4 were subjected to a dummy operation. were treated with daily e.c. injections for 4 weeks Evaluation: The animals were sacrificed with a C02 atmosphere after 4 weeks of treatment During the autopsy, the number of animals with or without endometriotic lesions was calculated. and the surface area and the volume were measured The expression of CCR1 mRNA and FIANTES in uterus, ovaries, peritoneal endometriotic cysts and rat mesenteries was analyzed and quantified as described in example 27. Example 30 Endometrosis was induced experimentally by inoculation of menstrual endometrium or by autologous transplantation as described in the literature (11, 12, 13, 14). Immunohistochemical analysis of CCR1 in grafts / endometriotic lesions was carried out as described in example 28. First part of the study: Treatment of endometrosis. After inducing endometrosis, primates were treated with different concentrations of the CCR1 antagonist for 2-3 weeks. As a control, the animals were treated with vehicle, GnRH antagonist and placebo. A video laparoscopy was performed to document the number, surface, volume and revised score of the American Fertility Society (rAFS) and stage of endometriotic lesions. All the laparoscopies were performed by a single investigator. Serum and blood samples were taken and analyzed before inducing the disease and during treatment. In the second part of the study, the animals were treated with CCR1 antagonist before inducing endometrosis, in particular with (2R) -l-. { [4-chloro-2-ureido) phenoxy] methyl} carbonyl-2-metii-4- 4-fluoro-benz-D-piperazine as the sulfate salt. At the end of the study, the endometriotic lesions underwent an ochronic analysis and biological molecular analysis.

Example 31 Efficacy of the CCRl antagonist according to the invention in the treatment of symptomatic endometrosis. The following clinical study was carried out to evaluate the efficacy of the CCR-1 antagonists according to the invention, in particular (2R) -l-. { [4-chloro-2- (ureido) phenoxy] methyl} carbonyl-2-yuelyl-4 ~ (4-fiuorobenzyl) piperazine as a sulfate salt, for the treatment of endometrosis and associated pelvic pain. A multicenter, placebo-controlled, randomized, double-blind study was designed in parallel groups with a population of fertile young women with historically confirmed endometritis at the age of 18-45 years, with or without infertility. The study was controlled with placebo, randomized, double-blind in parallel groups. The duration of the treatment was three months. The variable of primary efficacy is the change of pelvic pain according to a visual analogue scale. Secondary efficacy variables: Reduced absorption of co-medication for pelvic pain. Safety parameters: The physical and gynecological examination included breasts, laboratory safety, bleeding patterns (patient diary). The invention has just been described with reference to preferred embodiments. However, it is clear that the invention is susceptible to numerous variations within the doctrine of technical equivalents. Bibliography cited 1. Neote, K., DiGregorio, D., Mak, J.Y., Horuk, R., and Schall, T.J. 1993. Molecular cloning, functional expression, and signaling characteristics of a C-C chemokine receptor. Cell 72: 415-425. 2. Su, SB, Mukaida, N., Wang, J., Noraura, H., and Ma-tsushima, K. 1996. Preparation of specific polyclonal antibodies to a CC chemokine receptor, CCRl, and determination of CCRl expression on various types of leukocytes. J Leukoc Biol 60: 658-666. 3. Hornung, D., Ryan, I.P., Chao, V.A. , Vigne, J.L., Schriock, E.D., and Taylor, R.N. 1997. Immunolocalization and regulation of the chemokine RANTES in human endometrial ar.d endometrosis tissues and cells. J Clin Endocrinol Metab 81: 1621-1628. 4. Khorram, O., Taylor, R.N., Ryan, I.P., Schall, T.J., and Landers, D.V. 1993. Peritoneal fluid concentrations of tne cytckine RANTES ccrrelate with the severity of endometriosis. Am J Obstet Gynecol 169: 1545-1549. 5. Hornung, D., Bentzien, F., Wallwiener, D., Kiesel, L., and Taylor, R.N. 2001. Chemokine bioactivity of RANTES in endometriotic and normal endometrial stromal cells and peritoneal fluid. Mol Hum Reprod 7: 163-168. 6. Zhao, D., Lebovic, D.I., and Taylor, R.N. 2002. Long-term progestin treatment inhibits RANTES (regu- late on activation, normal T cell expressed and secreted) gene expression in human endometrial stromal cells. J Clin Endocrinol Metab 87: 2514-2519. 7. Altman, G.B., Gown, A.M., Luchtel, D.L., and Baker, C. 1999. RANTES production by cultured primate endometrial epithelial cells. Am J Reprod Immunol 42: 168-174. Cheret A., Le Grand R., Caufour P., Neildez O., Matheux F., Th odoro F., 8. Medcalf R.L., Richards R.I., Crawford R.J. and Hamilton J.A.1986. Suppression of urokinase-type plasminogen ac-tivator mRNA levéis in human fibrosarcoma cells and syno-vial fibroblasts by anti-mflapr.a ory glucocorticoids. EMBO J. 5 (9); 2217-22 9. Vaslin B., Dormont D. RANTES, IFN-gamma, CCRl, and CCR5 mRNA expression in blood, lymph node, and bronchoalveolar lavage .t.cr.cn clear cells during primary simian immunodeficiency virus infection of macaques . 1999. Virology. 15; 255 (2): 285-93. 10. Margulies B.J., Hauer D.A., Clements J.E. Identification and comparison of eleven rhesus macaque chemokine receptors. 2001. AIDS Res Hum Retroviruses. 1; 17 (10): 981-6. 11 D'Hooghe T.M., Bambra C.S., Raeymaekers B.M., De Jonge I., Lauweryns J.M., Koninckx P.R. Intrapelvic injection of menstrual endometrium causes endometrosis in baboons (Papio cynocephalus and Papio anubis) .1995. Am J Obstet "Gynecol.173 (1): 125-34 12 Zong L.L., Li Y.L., Wang L.X., Zou J., Li J., Li T. Di Yi Jun Yi Da Xue Xue Bao. Establishment of animal models of endometrosis in rhesus monkeys .2003.23 (10): 1006-9. 13 D'Hooghe T.M., Nugent N., Cuneo, S., Chai D., Deer, F., Debrock, S. Mwenda, J. (2001). Recombinant human TNF binding protein (r-hTBP-1) inhibits the development of endometrosis in baboons: a prospective, randomized, placebo-and drug-controlled study.Abstract for an oral presentation at the Annual Meeting of the American Socity for Reproduction Medecine, Orlando, USA October 22nd-24th. 14 Fa? Ieabas A.T., Brudney A., Gurates B., Chai D., Bu-lun S. 2002. A modified baboon model for endometrosis. Ann N and Asad Sci. 955: 308-317; discussion 340-2, 396-406.

Stoeckemann K., Hegele-Hartung C. Effects of progesterone antagonists onapristone and ZK 136799 on surgically induced endometrosis in intact cycling rats.Human Reproduction 1995 Dec; 10 (12): 3264-71 TABLE 1 Test compounds TABLE II

Claims

Claims 1. Use of a compound of the following formula (la) in the production of a medicament for the treatment and prevention of endometrosis in humans wherein: Rla 'is one or more substituents selected from the group consisting of oxo, halo, (C1-C8) alkyl, (C3-C10) ) cycloalkyl, (C3-C10) cycloalkyl (Cl-C8) alkyl, (C3-C10) cycloalkylamino (C1-C8) alkyl, ((C3-C10) (C 1 -C 8) alkyl) alkyl) amino (Cl-C 8) alkyl, halo (C 1 -C 8) alkyl, (C 2 -C 8) alkenyl, (C 2 -C 8) alkynyl, phenyl or optionally substituted naphthyl, (phenyl or optionally substituted naphthyl) (C 1 -C 8) alkyl, (optionally substituted phenyl or naphthyl) (C 2 -C 8) alkenyl, formyl, formyl (C 1 -C 8) alkyl, hydroxy (C 1 -C 8) alkyl , hydroxy (C2-C8) alkenyl, hydroxy (C2-C8) alkynyl, (hydroxy) (phenyl or optionally substituted naphthyl) (C1-C8) alkyl, (hydroxy) (C3-C10) cycloalkyl (C1-C8) alkyl, mercapto (Cl-C8) alkyl, cyano (C1-C8) alkyl, halo (Cl-Cd) alkylcarbonylamino (C1-C8) alkyl, ((Cl- C8) alkoxy) (optionally substituted phenyl or naphthyl) ( C1-C8) alkyl, (C1-C8) alkoxy (C1-C8) alkyl, (optionally substituted phenyl or naphthyl) oxy (Cl-C8) alkyl, (optionally substituted phenyl or naphthyl) (C1-C8) alkoxy (C1- C8) alkyl, (Cl-C8) alkylthio (C1-C8) alkyl, (C1-C8) alkylsulfinyl (C1-C8) alkyl, (C1-C8) alkylsulfonyl (Cl-) C8) alkyl, hydroxy (C1-C8) alkylthio (C1-C8) alkyl, amino (C1-C8) alkyl, mono (Cl-C8) alkylamino (Cl-C8) alkyl, di (C1-C8) alkylamino (C1- C8) alkyl, mono (optionally substituted phenyl or naphthyl) amino (C 1 -C 8) alkyl, mono (phenyl or optionally substituted naphthyl) (C 1 -C 8) alkylamino (C 1 -C 8) alkyl, (C 1 -C 8) alkylcarbonylamino ( C1-C8) alkyl, ((C1-C8) alkylcarbonyl) ((C1-C8) alkyl) amino (Cl-C8) alkyl, (C1-C8) azido alkyl, ureido (Cl- C8) alkyl, mono (Cl-C8) alkylureido (C1- C8) alkyl, di (Cl-C8) alkylureido (Cl-C8) alkyl, ((C1-C8) al-coxycarbonyl (C1-C8) alkyl) ureido (C1-C8) alkyl, (C1-C8) alkoxycarbonylamino (C1-C8) alkyl, hydroxy (C1-C8) alkylamino (C1-C8) alkyl, (phenyl or optionally substituted naphthyl) oxy (Cl-C8) alkylcarbonyloxy (C1-C8) alkyl, (Cl - C8) (C1-C8) alkoxy (C1-C8) alkylcarbonyloxy, (optionally substituted phenyl or naphthyl) (Cl-C8) (C1-C8) alkoxy (C1-C8) alkylcarbonyloxy, (C1-C8) alkylcarbonyl, (C1-C8) alkylcarbonyl (Cl-C8) alkyl, carboxy, (C1-C8) alkoxycarbonyl, (optionally substituted phenyl or naphthyl) (C1-C8) alkoxycarbonyl, (optionally substituted phenyl or naphthyl) (C1-C8) alkylcarbonyl, aminocarbonyl, mono (C1-C8) alkylaminocarbonyl, di (Cl-C8) alkylaminocarbonyl, mono (optionally substituted phenyl or naphthyl) aminocarbonyl, mono (optionally substituted phenyl or naphthyl) (Cl-C8) alkylaminocarbonyl, carboxy (C1-C8) alkyl , (C1-C8) alkoxycarbonyl (C1-C8) alkyl, (optionally substituted phenyl or naphthyl) (Cl-C8) alkoxycarbonyl (C1-C8) alkyl, aminocarbonyl (Cl-C8) alkyl, mono ( C1-C8) alkylaminocarbonyl (Cl-C8) alkyl, di (C1-C8) alkylaminocarbonyl (Cl-C8) alkyl, mono (optionally substituted phenyl or naphthyl) aminocarbonyl (C1-C8) alkyl, mono-phenyl or optionally substituted naphthyl) (C1 -C8) alkylaminocarbonyl (C1-C8) alkyl, (optionally substituted phenyl or naphthyl) sulfonyl, heterocyclyl of 3 to 15 members consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and ( 3 to 15 membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (C 1 -C 8) alkyl; one or more substituents selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, (C 1 -C 8) alkyl, mercapto, mercapto (C 1 -C 8) alkyl, (C 1 -C 8) alkylthio, (C 1 -C 8) alkylsulfinyl , (Cl-C8) alkylsufonyl, (Cl-C8) alkylthio (C1-C8) alkyl, (C1-C8) alkylsulfinyl (C1-C8) alkyl(C1-C8) alkylsulfonyl (C1-C8) alkyl, (C1-C8) alkoxy, (optionally substituted phenyl or naphthyl) oxy, halo (Cl-C8) alkyl, formyl, (C1-C8) alkyl, nitro, nitroso, cyano, (optionally substituted phenyl or naphthyl) (C1-C8) alkoxy, halo (Cl-C8) alkoxy, (C3-C10) cycloalkyl, (C3-C10) cycloalkyl (Cl- C8) alkyl, (hydroxy) ( C3-C10) cycloalkyl (Cl-C8) alkyl, (C3-C10) cycloalkylamino, (C3-C10) cycloalkylamino (C1-C8) alkyl, ((C3-C10) cycloalkyl (C1-C8) alkyl) amino, ((C3-C10) (C1-C8) cycloalkyl (alkyl) amino (C1-C8) alkyl, cyano (C1-C8) alkyl, (C2-C8) alkenyl, (C2-C8) alkynyl, phenyl or optionally substituted naphthyl, (phenyl or optionally substituted naphthyl) (C 1 -C 8) alkyl, (optionally substituted phenyl or naphthyl) (C 2 -C 8) alkenyl, hydroxy (C 1 -C 8) alkyl, (hydroxy) (optionally substituted phenyl or naphthyl) ( C1-C8) alkyl, hydroxy (C1-C8) alkylthio (Cl-C8) alkyl, hydroxy (C2-C8) alkenyl, hydroxy (C2-C8). alkynyl, (C1-C8) alkoxy (C1-C8) alkyl, ((C1-C8) alkoxy) (optionally substituted phenyl or naphthyl) (C1-C8) alkyl, (optionally substituted phenyl or naphthyl) oxy (C1-C8) alkyl, (optionally substituted phenyl or naphthyl) (C1-C8) (C1-C8) alkoxy alkyl, amino, mono (C1-C8) alkylamino, di (Cl-C8) alkylamino, mono-phenyl or optionally substituted naphthyl) amino, mono-phenyl or optionally substituted naphthyl) (C 1 -C 8) alkylamino, amino (C 1 -C 8) alkyl, mono (C 1 -C 8) alkylamino (C 1 -C 8) alkyl, di (C 1 -C 8) alkylamino (C 1 -C 8) alkyl, hydroxy (Cl-C8) (C1-C8) alkylamino alkyl, mono (optionally substituted phenyl or naphthyl) amino (C1-C8) alkyl, mono-phenyl or optionally substituted naphthyl) (Cl-C8.) Alkylamino (C1-C8) alkyl, ( C1-C8) alkylcarbonylamino, ((C1-C8) alkylcarbonyl) ((C1-C8) alkyl) amino, (C1-C8) alkylcarbonylamino (C1-C8) alkyl, ((C1-C8) alkylcarbonyl) ((C1-C8) alkyl) amino (Cl-C8) alkyl, (C1-C8) alkoxycarbonylamino, ((C1-C8) alkoxycarbonyl) ((C1-C8) alkyl) amino, ( C1-C8) alkoxycarbonylamino (C1-C8) alkyl, ((C1-C8) alkoxycarbonyl) ((C1-C8) alkyl) amino (C1-C8) alkyl, carboxy, (C1-C8) alkoxycarbonyl, ( optionally substituted phenyl or naphthyl) (C 1 -C 8) alkoxycarbonyl, (C 1 -C 8) alkylcarbonyl, (C 1 -C 8) alkylcarbonyl (C 1 -C 8) alkyl, (optionally substituted phenyl or naphthyl) carbonyl, (optionally phenyl or naphthyl) substituted) carbonyl (C1-C8) alkyl, (optionally substituted phenyl or naphthyl) (C1-C8) alkylcarbonyl, (optionally substituted phenyl or naphthyl) (Cl-C8) alkylcarbonyl (C1-C8) alkyl, carboxy (Cl-C8) alkyl-, (C1-C8) alkoxycarbonyl (C1-C8) alkyl, (phenyl or optionally substituted naphthyl) (Cl-C8) lcoxycarbony ((C1-C8) alkyl, (C1-C8) alkoxy (Cl-C8) alkylcarbonyloxy (C1-C8) alkyl, aminocarbonyl, mono (Cl-C8) alkylaminocarbonyl, di (Cl- C8) alkylaminocarbonyl, mono (optionally substituted phenyl or naphthyl) aminocarbonyl, mono (optionally substituted phenyl or naphthyl) (Cl-C8) alkylarainecarbonyl, aminocarbonyl (C1-C8) alkyl, mono (C1-C8) alkylaminocarbonyl ( C1-C8) alkyl, di (C1-C8) alkylaminocarbonyl (Cl-C8) alkyl, mono (phenyl or optionally substituted naphthyl) aminocarbonyl (Cl-C8) alkyl, mono (phenyl or optionally substituted naphthyl) (C7-C8) alkylaminocarbonyl (C1-C8) alkyl, amidino, guanidino, ureido, mono (C1-C8) alkylureido, di (C1-C8) alkylureido, ureido (C1-C8) alkyl, mono (Cl-Cd) alkylureido (Cl-C8) alkyl , di (C1-C8) alkylureido (C1-C8) alkyl, heterocyclyl of 3 to 15 members consisting of carbon atoms and between one and five heteroatoms selected from the group formed by nitrogen, oxygen and sulfur and (3-15 membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (C1-C8) alkyl; is a 3- to 15-membered carbocyclic ring system substituted by one or more substituents selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, (C 1 -C 8) alkyl, mercapto, mercapto (C 1 -C 8) alkyl, (Cl-C8) alkylthio, (C1-C8) alkylsulfinyl, (Cl-C8) alkylsufonyl, (optionally substituted phenyl or naphthyl) sulfonyl, - (C1-C8) alkylthio (Cl-C8) alkyl, (C1-C8) alkylsulfi -N (C1-C8) alkyl, (C1-C8) alkylsulfonyl (C1-C8) alkyl, (Cl-C8) alkoxy, hydroxy (C1-C8) alkoxy, (phenyl or optionally substituted naphthyl) oxy, halo (C1- C8) alkyl, formyl, (C 1 -C 8) alkyl, nitro, nitroso, cyano, (optionally substituted phenyl or naphthyl) (Cl-C 8) alkoxy, halo (C 1 -C 8) alkoxy, (C 1 -C 8) alkoxy, (C3-C10) cycloalkyl, (C3-CIO) cycloalkyl (Cl-C8) alkyl, (hydroxy) (C3-C10) cycloalkyl (Cl-C8) alkyl, (C3-CIO) cycloalkylamino, (C3-C10) cycloalkylamino ( C1-C8) alkyl, cyano (C1-C8) alkyl, (C2-C8) alkenyl, (C2-C8) alkynyl, f enyl or optionally substituted naphthyl, (optionally substituted phenyl or naphthyl) (C 1 -C 8) alkyl, (optionally substituted phenyl or naphthyl) (C 2 -C 8) alkenyl, hydroxy (C 1 -C 8) alkyl, (hydroxy) (phenyl or naphthyl optionally substituted) (C1-C8) alkyl, (mono (C1-C8) alkylamino) (optionally substituted phenyl or naphthyl) (C1-C8) alkyl, (hydroxy (C1-C8) alkyl) thio (C1-C8) alkyl, hydroxy (C2-C8) alkenyl, hydroxy (C2-C8) alkynyl, (C1-C8) alkoxy (Cl-C8) alkyl, ((C1-C8) alkoxy) (phenyl or optionally substituted naphthyl) (C1-C8) alkyl, (optionally substituted phenyl or naphthyl) oxy (C1-C8) alkyl, (optionally substituted phenyl or naphthyl) (Cl-C8) (C1-C8) alkoxy alkyl, amino, mono (Cl-C8) alkylamino, di (C1-C8) alkylamino, mono-phenyl or optionally substituted naphthyl) amino, mono-phenyl or optionally substituted naphthyl) (C 1 -C 8) alkylamino, amino (C 1 -C 8) alkylamino, (3 to 15 membered heterocyclyl consisting of carbon atoms and between no and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) amino, ((C3-C10) cycloalkyl (Cl-C8) alkyl) amino, alkylcarbonylamino, (C1-C8) al-coxycarbonylamino, (C2-C8) alkenylcarbonylamino, (C3-C10) cycloalkylcarbonylamino, (phenyl or optionally substituted naphthyl) carbonylamino, (3 to 15 membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylamino, halo (C1-C8) alkylcarbonylamino, (C1- C8) (C1-C8) alkoxy alkylcarbonylamino, (C1-C8) alkoxycarbonyl (C1-C8) alkylcarbonylamino, ((C1-C8) alkylcarbonyl) ((Cl-C8) alkyl) amino, ((C1-C8) alkoxycarbonyl ) ((Cl-C8) alkyl) amino, (C1-C8) alkylsulfonylamino, amino (Cl-C8) alkyl, mono (C1-C8) alkylamino (Cl-C8) alkyl, di (C1-C8) alkylamino (C1- C8) alkyl, hydroxy (C1-C8) alkylamino (C1-C8) alkyl, mono (phenyl or optionally substituted naphthyl) amino (C1-C8 ') alkyl, mono-phenyl or optionally substituted naphthyl) (C1-C8) alkylamino (C l-C8) alkyl, (C1-C8) alkylcarbonylamino (Cl-C8) alkyl, (optionally substituted phenyl or naphthyl) carbonylamino (C1-C8) alkyl, ((C1-C8) alkylcarbonyl) ((C1-C8) alkyl) amino (C1-C8) alkyl, ((C3-C10) cycloalkyl (C1-C8) alkyl) amino (C1-C8) alkyl, (C1-C8) alkoxycarbonylamino (Cl-C8) alkyl, (Cl-C8) alkoxycarbonyl ( C1-C8) alkylcarbonylamino (Cl-C8) alkyl, ((C1-C8) alkoxycarbonyl) ((C1-C8) alkyl) amino (C1-C8) alkyl, (C1-C8) alkylsulfonylamino (C1-C8) alkyl , ((C1-C8) alkylsulfonyl) ((Cl- C8) alkyl) amino (C1-C8) alkyl, (optionally substituted phenyl or naphthyl) sulfonylamino (Cl-C8) alkyl, ((optionally substituted phenyl or naphthyl) sulfonyl) ((C1-C8) alkyl) amino (C1-C8) alkyl, (3 to 15 membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) amino (C1-C8) alkyl, carboxy, (Cl-C8) alkoxycarbonyl, (phenyl) or optionally substituted naphthyl) (C1-C8) alkoxycarbonyl, (C1-C8) alkylcarbonyl, (optionally substituted phenyl or naphthyl) carbonyl, (optionally substituted phenyl or naphthyl) (C1-C8) alkylcarbonyl, (hydroxy (Cl-C8) alkoxy) carbonyl, carboxy (C1-C8) alkyl, (Cl-C8) alkoxycarbonyt (C1-C8) alkyl, (phenyl or optionally substituted naphthyl) (C1-C8) alkoxycarbonyl (Cl-C8) alkyl, (C1-C8) alkoxy (C1-C8) alkylcarbonyloxy (C1-C8) alkyl, di (Cl-C8) alkylaminocarbonyloxy (Cl-C8) alkyl, (C1-C8) alkylcarbonyl (C1-C8) alkyl, (phenyl or optionally substituted naphthyl) carbonyl (C1-C8) alkyl, (optionally substituted phenyl or naphthyl) (C1-C8) alkylcarbonyl (C1-C8) alkyl, aminocarbonyl, mono (C1-C8) alkylaminocarbonyl, di (Cl-C8) alkylaminocarbonyl, mono (optionally substituted phenyl or naphthyl) aminocarbonyl, mono-phenyl or optionally substituted naphthyl) (Cl-C8) alkylaminocarbonyl, (C 1 -C 8) aminocarbonyl aminocarbonyl, (mono (Cl ~ C8) alkylaminocarbonii (C 1 -C 8) ) alkyl) aminocarbonyl, (carboxy (Cl-C8) alkyl) aminocarbonyl, ((C1-C8) alkoxycarbonyl (C1-C8) alkyl) aminocarbonyl, (amino (Cl-C8) alkyl) aminocarbonyl, (hydroxy (C1- C8) alkyl) aminocarbonyl, (C 1 -C 8) aminocarbonyl, (C 1 -C 8) alkylaminocarbonyl (C 1 -C 8) alkyl, di (C 1 -C 8) alkylaminocarbonyl (C 1 -C 8) alkyl, mono (phenyl or optionally substituted naphthyl) do) aminocarbonyl (C 1 -C 8) alkyl, mono (phenyl or optionally substituted naphthyl) (C 1 -C 8) alkylaminocarbonyl (C 1 -C 8) alkyl, amidino, hydroxyamidino, guanidino, ureido, mono (C 1 -C 8) alkylureido, mono-phenyl or naphthyl optionally substituted) ureido, mono-phenyl or optionally substituted naphthyl) (C1-C8) alkylureido, monohalo (C1-C8) alkylurei (mono (C1-C8) alkyl) (mono (optionally substituted phenyl or naphthyl)) ureido, di (Cl-C8) alkylureido, di (optionally substituted phenyl or naphthyl) ureido, (halo (Cl-C8) alkylcarbonyl) ureido, ureido (C1-C8) alkyl, mono (C1-C8) alkylureido (C1-C8) alkyl, di (C1-C8) alkyl (C1-C8) alkyl, mono (phenyl or optionally substituted naphthyl) ureido ( C1-C8) alkyl, mono-phenyl or optionally substituted naphthyl) (Cl-C8) alkylureido (C1-C8) alkyl, monohalo (C1-C8) alkyl-alkididoalkyl, (halo (C1-C8) alkyl) ((Cl-C8) alkyl) (C 1 -C 8) -alkyl, ((Cl-C 1-6-alkoxycarbonyl (C 1 -C 8) alkyl) ureido (C 1 -C 8) alkyl, glycinamide, mono (C 1 -C 8) alkylglycinamide, aminocarbonylglycine-mido, (( C1-C8) (C1-C8) alkoxy alkylcarbonyl) glycine-mido, (aminocarbonyl) ((C1-C8) alkyl) glycinamide, ((C1-C8) alkoxycarbonyl (C1-C8) alkylcarbonyl) ((Cl- C8) alkyl ) glycinamide, ((C 1 -C 8) alkoxycarbonylamino (C 1 -C 8) alkylcarbonyl) glycinamide, (phenyl or naphthyl optionally and substituted) carbonylglycinamide, ((optionally substituted phenyl or naphthyl) carbonyl) ((C 1 -C 8) alkyl) glycinamide, (mono- phenyl or optionally substituted naphthyl) (Cl-C 8) alkylaminocarbonyl) glycinamide, (mono (phenyl or optionally substituted naphthyl) (Cl-C8) alkylaminocarbonyl) ((C 1 -C 8) alkyl) glycinamide, (mono (optionally substituted phenyl or naphthyl) aminocarbonyl) glycinamide, (mono (optionally substituted phenyl or naphthyl) aminocarbonyl) ((C 1 -C 8 ) Alkyl) glycinamide, glycine (C 1 -C 8) alkyl, alaninamide, mono (Cl-C 8) alkylalaninamide, alaninamide (Cl-Cd) alkyl, 3 to 15 membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms selected from the group formed

1. 0 for nitrogen, oxygen and sulfur and (heterocyclyl

3 to 15 members consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (Cl-C8) alkyl; 5 or R3 is a 3-15 membered heterocyclic ring system consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, substituted by one or more substituents selected from the group consisting of hydrogen, hydroxy, halo, (Cl-Cd) alkyl, (Cl-Cd) alkylsufonyl, (optionally substituted phenyl or naphthyl) sulfonyl, (Cl-) C8) alkoxy, hydroxy (Cl-Cd) alkoxy, halo (Cl-Cd) alkyl, formyl, nitro, cyano, halo (Cl-Cd) alkoxy, (C2-C8) alkenyl, (C2-C8) alkynyl , phenyl or optionally substituted naphthyl, (optionally substituted phenyl or naphthyl) (C 1 -C 8) alkyl, amino, mono (Cl-Cd) alkylamino, di (Cl-Cd) alkylamino, mono (phenyl or optionally substituted naphthyl) amino , (optionally substituted mono-phenyl or naphthyl) (Cl-C8) alkylamino, (C1-C8) alkylcarbonylamino, (Cl-C8) alkoxycarbonylamino, (C2-C8). alkenylcarbonylamino, (C3-C10) cycloalkylcarbonylamino, (optionally substituted phenyl or naphthyl) carbonylamino, halo (Cl-C8) alkylcarbonylamino, (C1-C8) alkoxy (Cl- Cd) alkylcarbonylamino, (Cl-Cd) alkoxycarbonyl (Cl) - Cd) alkylcarbonylamino, ((C1-C8) alkylcarbonyl (Cl- Cd) alkyl) amino, ((Cl-Cd) alkoxycarbonyl) ((Cl- Cd) alkyl) amino, (Cl-Cd) alkylsulfonylamino, amino (C1- C8) alkyl, (C1-C8) monoalkylamino alkyl, di (Cl- Cd) alkylamino (C1-C8) alkyl, (Cl-C8) alkylcarbonylamino (C1-C8) alkyl, (phenyl or optionally substituted naphthyl) carbonylamino (Cl-) Cd) alkyl, ((Cl-Cd) alkylcarbonyl) ((Cl-Cd) alkyl) amino (C1-C8) alkyl, (Cl-Cd) alkoxycarbonylamino (C1-C8) alkyl, carboxy, (Cl- Cd) alkoxycarbonyl, (optionally substituted phenyl or naphthyl) (C 1 -C 8) alkoxycarbonyl, (C 1 -C 8) alkylcarbonyl, (optionally substituted phenyl or naphthyl) carbonyl, (optionally substituted phenyl or naphthyl) (C 1 -C 8) alkylcarbonyl, aminocarbonyl, mono (Cl-Cd) al optionally substituted phenylaminocarbonyl, di (Cl-Cd) alkylaminocarbonyl, mono-phenyl or naphthyl) aminocarbonyl, aminocarbonyl (Cl-Cd) alkyl, mono (Cl-Cd) alkylaminocarbonyl (C 1 -C 8) alkyl, di (Cl-Cd) alkylaminocarbonyl ( Cl-Cd) alkyl, mono-phenyl or optionally substituted naphthyl) aminocarbonyl (C 1 -C 8) alkyl, guanidino, ureido, mono (Cl-C8) alkylureido, ureido (Cl-Cd) alkyl, mono (Cl-Cd) alkylureido ( Cl- Cd) alkyl, and glycinamide; R 4 is -O-, -N (R 7) -, -C (R 8) 2- or a bond; R5 is a (C1-C8) alkylene chain or a (C1-C8) alkylidene chain, or, if R4 is a bond, R5 is a chain

(C1-C8) alkylidene which is optionally substituted by (optionally substituted phenyl or naphthyl) or -N (R7) 2; or R4 and R5 together are -HC = CH- R6 is -C (0) -, -C (S) -, -CH2- or a bond; each R7 is independently selected from the group consisting of hydrogen, (Cl-C8) alkyl, phenyl or optionally substituted naphthyl, (optionally substituted phenyl or naphthyl) (C1-C8) alkyl, (Cl-C8) alkylcarbonyl, (Cl -Cd) alkylcarbonyl (Cl-Cd) alkyl,. (phenyl or optionally substituted naphthyl) (Cl-Cd) alkylcarbonyl, (optionally substituted phenyl or naphthyl) (C 1 -C 8) alkylcarbonyl (Cl-Cd) alkyl, aminocarbonyl, mono (C 1 -C 8) alkylaminocarbonyl, di (C 1 -) C8) alkylaminocarbonyl, and (Cl-Cd) alkoxycarbonyl; and each R8 is selected from the group consisting of hydrogen, (C1-C8) alkyl, phenyl or optionally substituted naphthyl, (optionally substituted phenyl or naphthyl) (Cl-Cd) alkyl, hydroxy, (Cl-Cd) alkoxy, hydroxy (C1-C8) alkyl, (C1-C8) alkoxy (C1-C8) alkyl, amino, mono (Cl-Cd) alkylamino, di (C1-C8) alkylamino, (C1-C8) alkylcarbonylamino, (C3-C10) ) cycloalkyl-carbonylamino, (C3-C10) cycloalkyl (C1-C8) alkylcarbonylamino, (C1-C8) alkoxycarbonylamino, (C1-C8) alkylsulfonylamino, (phenyl or optionally substituted naphthyl) ca-rbonylamino, (Cl- Cd) alkoxycarbonyl (Cl-Cd) alkylcarbonylamino, ((Cl-C8) alkylcarbonyl) ((C1-C8) alkyl) amino, (optionally substituted phenyl or naphthyl) (Cl-Cd) alkylcarbonylamino, (optionally substituted phenyl or naphthyl) (C1-C8) alkylcarbonyl) ((Cl- Cd) alkyl) amino, (C1-C8) alkylcarbonylamino (Cl-C8) alkyl, cycloalkylcarbonylamino (C1-C8) alkyl, (Cl- C8) alkoxycarbonylamino (Cl-Cd) alkyl , ((Cl-Cd) alkylcarb onil} ((Cl-Cd) alkyl) aminoalkyl, (optionally substituted phenyl or naphthyl) (Cl-Cd) alkylcarbonylamino (Cl-Cd) alkyl, (3 to 15 membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms. selected from the group consisting of nitrogen, oxygen and azu-fre) carbonylamino (Cl-Cd) alkyl, ((phenyl or optionally substituted naphthyl) (Cl- Cd) alkylcarbonyl) ((Cl-Cd) alkyl) amino (Cl- Cd) alkyl, (phenyl or optionally substituted naphthyl) sulfonylamino, (Cl- Cd) alkylsulfonylamino (C 1 -C 8) alkyl, ureido, mono (Cl-Cd) alkylureido, monohalo (Cl-Cd) alkylureido, di (Cl-Cd) alkylureide, ureido (Cl-Cd) alkyl, mono (Cl-Cd) alkylureido (C1-C8) alkyl, di (Cl-Cd) alkylureido (C1-C8) alkyl, monohalo (Cl-C8) alkylureido (C1-C8) alkyl, amino (C1-C8) alkyl, mono (Cl-Cd) alkylamino (Cl-Cd) alkyl, di (Cl- C8) alkylamino (C1-C8) alkyl, carboxy (Cl-Cd) alkyl, (Cl-Cd) ) alkoxycarbonyl (Cl-Cd) alkyl, aminocarbonyl (Cl-Cd) alkyl, mono (Cl-Cd) alkylaminocarbonyl (C 1 -C 8) alkyl, and di (Cl-Cd) alkylaminocarbonyl (Cl-Cd) alkyl; with the proviso that when R 4 is -N (R 7) -, R 3 can not be a heterocyclic ring system containing between 4 and 8 members consisting of carbon atoms and only one nitrogen atom; and with the proviso that when R4 is -C (R8) 2 or a bond, R3 can not be a saturated 4-6 membered heterocyclic ring system consisting of carbon atoms and two nitrogen atoms, and unique stereoisomer or a mixture thereof; or an acceptable salt for pharmaceutical use thereof.

2. The compound of claim 1 wherein: R3 is a 3- to 15-membered carbocyclic ring system substituted by one or more substituents selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, (C1-C8) alkyl, mercapto, mercapto (Cl-Cd) alkyl, (Cl-C8) alkylthio, (C1-C8) alkylsulfinyl, (Cl-Cd) alkylsulfonyl, (optionally substituted phenyl or naphthyl) sulfonyl, (Cl-Cd) alkylthio ( Cl- Cd) alkyl, (C1-C8) alkylsulfinyl (C1-C8) alkyl, (C1-C8) alkylsulfonyl (C1-C8) alkyl, (Cl- Cd) alkoxy, hydroxy (C1-C8) alkoxy, (phenyl or optionally substituted naphthyl) oxy, halo (Cl-Cd) alkyl, formyl, (C1-C8) alkyl, nitro, nitroso, cyano, (optionally substituted phenyl- or naphthyl) (Cl- Cd) alkoxy, halo (C1- C8) alkoxy, amino (Cl-Cd) alkoxy, (C3-C10) cycloalkyl, (C3-CIO) cycloalkyl (Cl- Cd) alkyl, (hydroxy) (C3-C10) cycloalkyl (Cl-'20 Cd) alkyl, (C3-CIO) cycloalkylamino, (C3- "

C10) cycloalkylamino (Cl-Cd) alkyl, cyano (Cl-Cd) alkyl, (C2-C6) alkenyl, (C2-C8) alkynyl, phenyl or optionally substituted naphthyl, (optionally substituted phenyl or naphthyl) (C1- C8) alkyl, (optionally substituted phenyl or naphthyl) (C2-Cd) alkenyl, hydroxy (C1-C8) alkyl, (hydroxy) (phenyl or optionally substituted naphthyl) (Cl-Cd) alkyl, (mono (C1- C8) alkylamino) (optionally substituted phenyl or naphthyl) (C1-C8) alkyl, (hydroxy (C1-C8) alkyl) thio (Cl-Cd) alkyl, hydroxy (C2-C8) alkenyl, hydroxy (C2-C8) alkynyl, (C1-C8) alkoxy (C1-C8) alkyl, ((C1-C8) alkoxy) (optionally substituted phenyl or naphthyl) (Cl- Cd) alkyl, (optionally substituted phenyl or naphthyl) oxy (Cl-) Cd) alkyl, (optionally substituted phenyl or naphthyl) (Cl-Cd) alkoxy (Cl-Cd) alkyl, amino, mono (Cl-C8) alkylamino, di (Cl- Cd) alkylamino, mono (phenyl or naphthyl optionally

- substituted) amino, mono (optionally substituted phenyl or naphthyl) (C 1 -C 8) alkylamino, amino (Cl-Cd) alkylamino, heterocyclyl of 3 to 15 members consisting of carbon atoms and between one and five heteroatoms selected from the group formed by nitrogen, oxygen and sulfur, amino, ((C3-C10) cycloalkyl (Cl- Cd) alkyl) amino, (C1-C8) alkylcarbonylamino, (C1-C8) alkoxycarbonylamino, (C2- C8) alkenylcarbonylamino, (C3-C10) cycloalkylcarbonylamino, (optionally substituted phenyl or naphthyl) carbonylamino, (3 to 15 membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylamino, halo (C1-) C8) alkylcarbonylamino, (Cl-C8) (C1-C8) alkoxy alkylcarbonylamino, (Cl-Cd) alkoxycarbonyl (C1-C8) alkylcarbonylamino, ((Cl-C8) alkylcarbonyl) ((C1-C8) alkyl) amino, ((Cl-Cd) alkoxycarbonyl) ((Cl-Cd) alkyl) amino, (Cl-Cd) alkylsulfonylamino, amino (C1-C8) alkyl or, mono (Cl-Cd) alkylamino (C1-C8) alkyl, di (C1-C8) alkylamino (C1-C8) alkyl, hydroxy (C1-C8) alkylamino (Cl-C8) alkyl, mono (phenyl or naphthyl optionally substituted) amino (Cl-Cd) alkyl, mono- phenyl or optionally substituted naphthyl) (C 1 -C 8) alkylamino (C 1 -C 8) alkyl, (C 1 -C 8) alkylcarbonylamino (C 1 -C 8) alkyl, '(phenyl or naphthyl optionally sus- substituted) carbonylamino (Cl-Cd) alkyl, ((Cl- Cd) alkylcarbonyl) ((-C1-C8) alkyl) amino (Cl-Cd) alkyl, (C 1 -C 8) alkyl) amino) (C 1 -C 8) alkyl alkyl, (Cl-Cd) alkoxycarbonylamino (Cl- Cd) alkyl, (C1-C8) alkoxycarbonyl (C1-C8) alkylcarbonylamino (Cl- Cd) alkyl, ((Cl-Cd) alkoxycarbonyl) ((C1-C8) alkyl) amino (Cl-Cd) alkyl, (C1-C8) alkylsulfonylamino (C1-C8) alkyl, ((C1-C8) alkylsulfonyl) ((Cl- 5 C8) alkyl) amino (Cl-Cd) alkyl, (phenyl or naphthyl) optionally substituted) sulfonylamino (Cl- Cd) alkyl, ((phenyl or optionally substituted naphthyl) sulfonyl) ((C 1 -C 8) alkyl) amino (Cl-Cd) alkyl, (heterocyclyl of 3 to 15 members that

10. consists of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) amino (C1-C8) alkyl, carboxy, (Cl-Cd) alkoxycarbonyl, (optionally substituted phenyl or naphthyl) (C1-C8 alkoxycarbonyl,

15 (C1-C8) alkylcarbonyl, (optionally substituted phenyl or naphthyl) carbonyl, (optionally substituted phenyl or naphthyl) (Cl-Cd) alkylcarbonyl, (hydroxy (C1-C8) alkoxy) carbonyl, carboxy (C1-C8) alkyl, (C1-C8) alkoxycarbonyl (Cl-Cd) alkyl, (optionally substituted phenyl or naphthyl) (Cl-Cd) alkoxycarbonyl (C1-C8) alkyl, (C1-C8) alkoxy (Cl-Cd) alkylcarbonyloxy (Cl-) Cd) alkyl, di (Cl-Cd) alkylaminocarbonyloxy (C1-C8) alkyl, (Cl-C8) alkylcarbonyl (C1-C8) alkyl, (phenyl or optionally substituted naphthyl) carbonyl (C1-C8) alkyl, (phenyl) or optionally substituted naphthyl) (Cl-C8) alkylcarbonyl (C1-C8) alkyl, aminocarbonyl, mono (C1-C8) alkylaminocarbonyl, dl (Cl-C8) alkylaminocarbonyl, mono-phenyl or optionally substituted naphthyl) aminocarbonylg, (optionally substituted mono- phenyl or naphthyl) (C 1 -C 8) alkylaminocarbonyl, (C 1 -C 8) aminocarbonyl aminocarbonyl, (mono (Cl-Cd) alkylaminocarbonyl (Cl- Cd) alkyl) aminocarbonyl, (carboxy (Cl-Cd) alkyl) aminocarbonyl, ((Cl-Cd) alkoxycarbonyl (Cl-Cd) alkyl) aminocarbonyl, (amino (Cl-Cd) alkyl) aminocarbonyl, (hydroxy (Cl-Cd) alkyl) aminocarbonyl, aminocarbonyl (Cl-Cd) alkyl , mono (Cl-Cd) alkylaminocarbonyl (C 1 -C 8) alkyl, di (C 1 -C 8) alkylaminocarbonyl (Cl-Cd) alkyl, mono (optionally substituted phenyl or naphthyl) aminocarbonyl (C 1 -C 8) alkyl, mono-phenyl or optionally substituted naphthyl ) (Cl-C8) alkylaminocarbonyl (C1-C8) alkyl, amidino, hydroxyamidino, guanidino, ureido, mono (Cl-Cd) alkylureido, mono-phenyl or optionally substituted naphthyl) ureido, mono-phenyl or optionally substituted naphthyl) (Cl-C8) ) alkylureido, monohalo (Cl-Cd) alkylureido, (mono (C1-C8) alkyl) (mono-phenyl or optionally substituted naphthyl)) ureido, d i (Cl-Cd) alkylureido, di (phenyl or optionally substituted naphthyl) ureido, (halo (Cl- Cd) alkylcarbonyl) ureido, ureido (Cl-Cd) alkyl, mono (Cl-Cd) alkylureido (Cl-) Cd) alkyl, di (Cl- Cd) alkylureido (Cl-Cd) alkyl, mono (phenyl or optionally substituted naphthyl) ureido (C 1 -C 8) alkyl, mono (phenyl or optionally substituted naphthyl) (Cl- Cd) alkyl (C 1 -C 8) alkyl, monohalo (Cl-Cd) alkylureido (Cl-Cd) alkyl, (halo (Cl-Cd) alkyl) ((Cl-Cd) alkyl) ureido (C 1 -C 8) alkyl, ((C1 -C8) alkoxycarbonyl (C1-C8) alkyl) ureido (Cl-1.5 C8) alkyl, glycinamide, mono (C1-C8) alkylglycinamido, "aminocarbonylglycinamide, ((C1-C8) alkoxy (C1-C8) alkylcarbonyl) glycinamide , (aminocarbonyl) ((Cl-Cd) alkyl) glycinamide, ((Cl- C8) alkoxycarbonyl (Cl-Cd) alkylcarbonyl) ((Cl-0 Cd) alkyl) glycinamide, ((C 1 -C 8) alkoxycarbonylamino (C 1 -C 8) alkylcarbonyl) glycinamide, (phenyl or optionally substituted naphthyl) carbonylglycinamide, ((phenyl or naphthyl opium) (optionally substituted) carbonyl) ((C1-C8) alkyl) glycinamide, (mono- phenyl or optionally substituted naphthyl) (Cl- Cd) alkylaminocarbonyl) glycinamide, (mono (optionally substituted phenyl or naphthyl) (Cl- Cd) alkylaminocarbonyl) ( (Cl-Cd) alkyl) glycinamide,

(mono (optionally substituted phenyl or naphthyl) aminocarbonyl) glycinamide, (mono (optionally substituted phenyl or naphthyl) aminocarbonyl) ((C 1 -C 8) alkyl) glycinamide, glycinamide (Cl-C) alkyl, alanaminamide, mono (Cl-) Cd) alkylalaninamido, alaninamido (C1-C8) alkyl, heterocyclyl of 3 to 15 members consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and (heterocyclyl of 3 to 15 members consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (Cl-Cd) alkyl.

3. The compound of claim 2 wherein: R4 is -O-, -N (R7) - or -C (R8) -; R5 is a (Cl-Cd) alkylene chain;

R7 is selected from the group consisting of hydrogen, (Cl-Cd) alkyl, phenyl or optionally substituted naphthyl, (optionally substituted phenyl or naphthyl) (C1-C8) alkyl, (Cl-Cd) alkylcarbonyl, (Cl- Cd) alkylcarbonyl (Cl-Cd) alkyl, (optionally substituted phenyl or naphthyl) (C1-C8) alkylcarbonyl, (optionally substituted phenyl or naphthyl) (Cl-C8) alkylcarbonyl (C1-C8) alkyl, aminocarbonyl, mono (C1-C8) alkylaminocarbonyl, di (Cl-C) alkylaminocarbonyl, and (Cl-Cd) alkoxycarbonyl; and each R8 is selected from the group consisting of hydrogen, (Cl-Cd) alkyl, phenyl or optionally substituted naphthyl, (optionally substituted phenyl or naphthyl) (C1-C8) alkyl, hydroxy, (Cl-Cd) alkoxy, hydroxy ( C1-C8) alkyl, (Cl-Cd) alkoxy (Cl-Cd) alkyl, amino, mono (C1-C8) alkylamino, di (Cl-C8) alkylamino, (C1-C8) alkylcarbonylamino, (C3-C10) cycloal --carbonylamino, (C3-C10) cycloalkyl (Cl-Cd) alkylcarbonylamino, (Cl-Cd) alkoxycarbonylamino, (Cl-Cd) alkylsulfonylamino, (optionally substituted phenyl or naphthyl) carbonylamino, (C1-C8) alkoxycarbonyl (C1- C8) alkylcarbonylamino, ((Cl-Cd) alkylcarbonyl) ((Cl-Cd) alkyl) amino, (optionally substituted phenyl or naphthyl) (Cl-Cd) alkylcarbonylamino, ((optionally substituted phenyl or naphthyl) (C1 -C8) alkylcarbonyl) ((Cl-Cd) alkyl) amino, (C1-C8) alkylcarbonylamino (Cl-Cd) alkyl, (C3-C10) cycloalkylcarbonylamino (Cl-Cd) alkyl, (Cl-Cd) alkoxycarbonylamino (C1-) C8) alkyl, ((C1-C8) alkylcarb onyl) ((Cl-C8) alkyl) amino (Cl-Cd) alkyl, (optionally substituted phenyl or naphthyl) (C 1 -C 8) alkylcarbonylamino (C 1 -C 8) alkyl, (3 to 15 membered heterocyclyl consisting of carbon and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylamino (C 1 -C 8) alkyl, ((phenyl or optionally substituted naphthyl) (Cl-Cd) alkylcarbonyl) ((C 1 -C 8) alkyl amino (Cl-Cd) alkyl, (optionally substituted phenyl or naphthyl) sulfonylamino, (Cl-Cd) alkylsulfonylamino (Cl-Cd) alkyl, ureido, mono (Cl-Cd) alkylureido, mono-halo (Cl-Cd) alkylureido , di (Cl-Cd) alkylureido, ureido (Cl-Cd) alkyl, mono (Cl-Cd) alkylureido (Cl-Cd) alkyl, di (Cl-C8) alkylureido (C1-C8) alkyl, monohalo (C1-C8) ) alkylureide (Cl-Cd) alkyl, amino (Cl-Cd) alkyl, mono (C1-C8) alkylamino (Cl-Cd) alkyl, di (Cl-Cd) alkyl (C1-C8) alkyl, carboxy (C1-C8) ) alkyl, (C1-C8) alkoxycarbonyl4 (Cl- Cd) alkyl, aminocarbonyl (C1-C8) alkyl, mono (Cl-C8) alkylaminocarbonyl (C1-C8) alkyl, and di (Cl-C8) alkylaminocarbonyl (C1-C8) alkyl.

4. The compound of claim 3 wherein: R 4 is -O-; R ° is methylene; and Rd is -C (O) -. The compound of claim 4, wherein: R la is one or more substituents selected from the group consisting of halo, (C 1 -C 8) alkyl, (C 3 -C 10) cycloalkyl, (C 3 -C 10) cycloalkylamino (C 1) -C8) alkyl, halo (Cl-Cd) alkyl, hydroxy (Cl-Cd) alkyl,

• hydroxy (C2-C8) alkenyl, hydroxy (C2-C8) alkynyl, (hydroxy) (phenyl or optionally substituted naphthyl) (Cl-Cd) alkyl, cyano (C1-C8) alkyl, halo (Cl- C8) alkylcarbonylamino ( Cl-Cd) alkyl, (Cl-Cd) alkoxy (Cl-C) alkyl, (optionally substituted phenyl or naphthyl) (C 1 -C 8) alkoxy (C 1 -C 8) alkyl, (Cl-Cd) alkylthio (Cl-Cd) alkyl, hydroxy (Cl-Cd) alkylthio (C1-C8) alkyl, amino (C1-C8) alkyl, mono (Cl- Cd) alkylamino (C1-C8) alkyl, di (C1-C8) alkylamino (Cl-Cd) alkyl, mono (optionally substituted phenyl or naphthyl) amino (Cl-Cd) alkyl, mono-phenyl or optionally substituted naphthyl) (Cl-Cd) alkylamino (C1-C8) alkyl, azido (Cl-Cd) alkyl, mono (Cl-Cd) alkylureido (C1-C8) alkyl, ((Cl-Cd) alkoxycarbonyl (C1-C8) alkyl) ureido (C1-C8) alkyl, -hydroxy (Cl -Cd) alkylamino (C1-C8) alkyl, (optionally substituted phenyl or naphthyl) oxy (Cl-C8) alkylcarbonyloxy (C1-C8) alkyl, (phenyl or optionally substituted naphthyl) (C1-C8) alkoxy (Cl-C8) alkylcarbonyloxy (Cl-Cd) alkyl, (Cl-Cd) alkylcarbonyl (Cl-Cd) alkyl, (Cl-Cd) alkoxycarbonyl, (C 1 -C 8) alkoxycarbonyl (Cl-Cd) alkyl, and (heterocyclic from 3 to 15 members consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur e) (Cl-Cd) alkyl;

R is one or more substituents selected from the group consisting of hydrogen and halo; R3 is phenyl which is optionally substituted by one or more substituents selected from the group consisting of hydrogen, hydroxy, halo, (Cl-Cd) alkyl, (Cl-Cd) alkoxy, hydroxy (C1-C8) alkoxy, halo (Cl-) C8) alkyl, formyl, nitro, cyano, amino (-Cl- C8) alkoxy, (C3-C10) cycloalkyl, (C3-C10) cycloalkylamino (C1-C8) alkyl, (phenyl or optionally substituted naphthyl) (C1-C8) alkyl, hydroxy (C1-C8) alkyl, (mono (Cl-Cd) alkylamino) (phenyl or optionally substituted naphthyl) (Cl-C8) alkyl, (Cl- Cd) alkoxy (Cl-Cd) alkyl, amino, mono (Cl-Cd) lyalkylamino, di (C1-C8) alkylamino, mono-phenyl or optionally substituted naphthyl) (Cl-Cd) alkylamino, (Cl-Cd) alkylcarbonylamino, (C2-Cd) alkenylcarbonylamino, (C3-C10) cycloalkylcarbonylamino , (optionally substituted phenyl or naphthyl) carbonylamino, (3 to 15 membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylamino, halo (Cl-Cd) alkylcarbonylamino, (C 1 -C 8) alkoxy (C 1 -C 8) alkylcarbonylamino, (Cl-Cd) alkoxycarbonyl (Cl-Cd) alkylcarbonylamino, ((Cl-C8) alkylcarbonyl) (( C1-C8) alkyl) amino, (Cl-Cd) alkylsulfonylamino, amino (C1-C8) alkyl, mono (Cl-C8) alkylamino (C1-C8) alkyl, di (C1-C8) alkylamino (Cl-Cd) alkyl , mono (optionally substituted phenyl or naphthyl) amino (C 1 -C 8) alkyl, mono (optionally substituted phenyl or naphthyl) (Cl-Cd) alkylamino (Cl-Cd) alkyl, (C 1 -C 8) alkylcarbonylamino (C 1 -C 8) alkyl , (optionally substituted phenyl or naphthyl) carbonylamino (C 1 -C 8) alkyl, ((Cl-Cd) alkylcarbonyl) ((Cl-Cd) alkyl) amino (Cl-Cd) alkyl, (cycloal-qui (Cl-Cd) alkyl amino (C1-C8) alkyl, (Cl-CS) alkoxycarbonylamino (C1-C8) alkyl, (Cl-Cd) alkoxycarbonyl (C1-C8) aicylcarbonylamino (Cl-Cd) alkyl, ((C1-C8) alkoxycarbonyl) ( (Cl-Cd) alkyl) amino (C1-C8) alkyl, (Cl-Cd) alkylsulfo-nylamino (Cl-C8) alkyl, ((Cl-Cd) alkylsulfonyl) ((C1-C8) alkyl) amino (C 1 -C 8) alkyl, (optionally substituted phenyl or naphthyl) sulfonylamino (Cl-Cd) alkyl, ((optionally substituted phenyl or naphthyl) sulfonyl) ((Cl- Cd) alkyl) amino (Cl-) Cd) alkyl, (3- to 15-membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) amino (C 1 -C 8) alkyl, carboxy, (Cl-Cd) alkoxycarbonyl , (Cl-Cd) alkylcarbonyl, (hydroxy (Cl-Cd) alkoxy) carbonyl, aminocarbonyl, mono (Cl-Cd) alkylaminocarbonyl, mono (phenyl or optionally substituted naphthyl) aminocarbonyl, (aminocarbonyl (Cl-Cd) alkyl) aminocarbonyl, (amino (Cl- Cd) alkyl) aminocarbonyl, (hydroxy (C1-C8) alkyl) aminocarbonyl, di (C1-C8) alkylaminocarbonyl (Cl-C8) alkyl, hydroxyamidino, ureido, mono (Cl-C8) alkylureido, optionally substituted mono-phenyl or naphthyl) ureido, mono-phenyl or optionally substituted naphthyl) (Cl-Cd) alkylureido, (mono (Cl-C8) alkyl) (mo nopephenyl or optionally substituted naphthyl)) ureido, (halo (C 1 -C 8) alkylcarbonyl) ureido, ureido (Cl-Cd) alkyl, "mono (Cl-Cd) alkylureido (Cl- Cd) alkyl, di (Cl-Cd) alkylureido (C1-C8) alkyl, mono (optionally substituted phenyl or naphthyl) ureido (C1-C8) alkyl, mono-phenyl or optionally substituted naphthyl) (C1-C8) alkylureido (C1-C8) alkyl, monohalo (C1-C8) alkyl (C 1 -C 8) alkyl, (halo (C 1 -C 8) alkyl) ((C 1 -C 8) alkyl) ureido (C 1 -C 8) alkyl, ((C 1 -C 8) alkoxycarbonyl (C 1 -C 8) alkyl) ureido (C 1) -C8) alkyl, glycinamide, mono (C1-C8) alkylglycinamido, aminocarbonylglycinamide, ((C1-C8) alkoxy (Cl-Cd) alkylcarbonyl) glycine, (aminocarbonyl) ((Cl-Cd) alkyl) glycinamide, ((Cl-Cd) (C 1 -C 8) alkoxycarbonyl) ((Cl-C8) alkyl) glycinamide, ((Cl-Cd) alkoxycarbonylamino (C 1 -C 8) alkylcarbonyl) glycinamide, (optionally substituted phenyl or naphthyl) carbonylglycinamide, ((optionally substituted phenyl or naphthyl) carbonyl) ((Cl-C8) alkyl) glycinamide, (mono (optionally substituted phenyl or naphthyl) (C1-C8) alkylaminocarbonyl) glycinamide, (mono- phenyl or optionally substituted naphthyl) (C1-C8) alkylaminocarbonyl) ((Cl-Cd) alkyl) glycinamide, (mono-phenyl or optionally substituted naphthyl) aminocarbonyl) glycinamide, (mono (optionally substituted phenyl or naphthyl) aminocarbonyl) ((C 1 -C 8) alkyl) glycinamide, alaninamide, heterocyclyl from 3 to 15 members consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, and (3- 15 membered heterocyclyl consisting of carbon atoms and • 5 between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (Cl-Cd) alkyl. 6. The compound of claim 5 selected from the group consisting of the following compounds: 0 (25) -l- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; 1- ((phenoxy) methyl) carbonyl-2-ethyl-4- (4-fluorobenzyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-5-ethylpiperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (methoxymethyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- ((acetylamino) methyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-2- (2- ((4-fluorobenzyl) amino) ethyl) -4- (4-fluorobenzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-2- (2- ((methyl) amino) ethyl) -4- (4-fluorobenzyl) piperazine;

1- ((4-chlorophenoxy) methyl) carbonyl-2- (2- ((2-hydroxy-ethyl) amino) ethyl) -4- (4-fluorobenzyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (((((4-chlorophenoxy) methyl) carbonyl) oxy) methyl-5-methylpiperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (ethoxycarbonyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (methoxycarbonyl) methylpiperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- ((methoxy) methyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2- (methoxy) ethyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxy-2- (4-methylphenyl) ethyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxypropyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxybut-4-ynyl) piperazine; 4 ~ (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-5- (2-hydroxy-2-methylpropyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxyethyl) piperazine;

1- ((4-chlorophenoxy) methyl) carbonyl-3- (2- ((2-hydroxy-ethyl) amino) ethyl) -4- (4-fluorobenzyl) piperazine; (cis) -4- (4-fluorobenzyl) -1- ((-chlorophenoxy) methyl) carbonyl-2, 3-dimethylpiperazine; (2S, 51?) -1- ((4-chloro-3,5-dimethoxyphenoxy) methyl) carbonane-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (25, 55) -4- (4-fluorobenzyl) -l- ((4-chlorophenoxy) methyl) carbonyl-2,5-dimethylpiperazine; (2R, 5S) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5- (2-methylthio) ethylpiperazine; (21? 51?) -4- (4-Fluorobenzyl) -! - ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5- (benzyloxy) methylpyrrazine; (21? 51?) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- (((2-hydroxyethyl) thio) methyl) piperazine; - (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl- 2- (N '- (ethoxycarbonylmethyl) ureido) methyl) piperazine; (21 ?, 55) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5- ((amino) carbonyloxy) methyl-4- (4-fluorobenzyl) piperazine;

4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- ((acetyl) methyl) piperazine; (21? 51?) -4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5 - (1-hydroxy-1- (phenyl) methyl) iperazine; (21? 51?) -4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) methyl) 'carbonyl-2-methyl-5- (1-hydroxybutyl) piperazine; (21? 5 5) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((diethylamino) methyl) piperazine; (21? 5S) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((dimethylamino) methyl) piperazine; (2J ?, 5S) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((cyclopropyl) amino) methyl) piperazine; (21? 5S) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5 ((morpholin-4-yl) methyl) piperazine; (21? 51?) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4 ~ (4-fluorobenzyl) -5- ((piperazin-1-yl) methyl) piperazine; (cis) -1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-2,6-dimethyl-4- (4-fluorobenzyl) piperazine; (cis) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) -carbonyl-2,6-dimethylpiperazine; 1- ((phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; 1- ((2- (acetylamino) phenoxy) methyl) carboni1-2-methyl-4- (4-fluorobenzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-2- (2-hydroxypropyl) -4- (4-fluorobenzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-2- (2-hydroxybut-3-enyl) -4- (4-fluorobenzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-3-trifluoromethyl-4- (4-fluorobenzyl) -perazine; and (trans) -1- ((4-chloro-2- ((4- (2,5-di (trifluoromethyl) phenylcarbonyl) piperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2, 5-dimethyl- 4- (4- fluorobenzyl) piperazine. 7. The compound of claim 5, wherein: Rla is one or more substituents selected from the group consisting of (C1-C8) alkyl, (C3-C10) cycloalkyl, hydroxy (Cl-Cd) alkyl, hydroxy (C2-C8) alkenyl, cyano (Cl-Cd) alkyl, (C1-C8) alkoxy (Cl- Cd) alkyl, mono (Cl-Cd) alkylamino (C1-C8) alkyl, azido (C1-C8) alkyl, mono (Cl-C8) alkylureido (Cl-Cd) alkyl, (optionally substituted phenyl or naphthyl) oxy (Cl-Cd) alkylcarbonyloxy (Cl-Cd) alkyl, and (3- to 15-membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (Cl-Cd) alkyl; one or more substituents selected from the group consisting of hydrogen, chloro or fluoro; R 3 is phenyl substituted by one or more substituents selected from the group consisting of hydroxy, halo, (C 1 -C 8) alkyl, (C 1 -C 8) alkoxy, formyl, nitro, cyano, amino (C 1 -C 8) alkoxy, (C 3) - CIO) cycloalkylamino (C1-C8) alkyl, hydroxy (Cl-Cd) alkyl, (mono (C1-C8) alkylamino) (phenyl or optionally substituted naphthyl) (C1-C8) alkyl, (Cl- Cd) alkoxy (C1 -C8) alkyl, amino, mono (Cl-Cd) alkylamino, di (Cl-C8) alkylamino, mono (phenyl or optionally substituted naphthyl) (C1-C8) alkylamino, (C1-C8) alkylcarbonylamino, (C2-) C8) alkenylcarbonylamino, (C3-CIO) cycloalkylcarbonyl amino, (optionally substituted phenyl or naphthyl) carbonylamino, (3- to 15-membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbo-nylamino, halo (Cl-Cd) alkylcarbonylamino, (C 1 -C 8) alkoxy (Cl-C8) alkylcarbonylamino, (C 1 -C 8) alkoxycarbonyl (Cl-Cd) alkylcarbonylamino, (C 1 -C 8) alkoxy uylsulfonylamino, amino (C1-C8) alkyl, mono (Cl- C8) alkylamino (Cl-Cd) alkyl, di (Cl-Cd) alkylamino (Cl-Cd) alkyl, mono- phenyl or optionally substituted naphthyl) (C1-C8) ) alkylamino (C1-C8) alkyl, (C1-C8) alkylcarbonylamino (Cl-Cd) alkyl, (phenyl or optionally substituted naphthyl) carbonylamino (Cl-C8) alkyl,, '((C1-C8) alkylcarbonyl) ((Cl -C8) alkyl) amino (Cl-Cd) alkyl, (cycloalkyl (Cl-Cd) alkyl) amino (Cl-Cd) -alkyl, (Cl-Cd) alkoxycarbonyl (Cl-Cd) alkylcarbonylamino (Cl-Cd) alkyl, (Cl-Cd) alkylsulfonylamino (Cl-Cd) alkyl, ((Cl-Cd) alkylsulfonyl) ((Cl-Cd) alkyl) amino (Cl-Cd) alkyl, (optionally substituted phenyl or naphthyl) sulfonylamino (Cl-Cd) alkyl, ((optionally substituted phenyl or naphthyl) sulfonyl) ((Cl-Cd) alkyl) amino (C1-C8) alkyl, carboxy, (Cl- C8) alkoxycarbonyl, (C1-C8) alkylcarbonyl, (hydroxy (Cl-Cd) ) lcoxy) carbonyl, aminocarbonyl, mono (C 1 -C 8) alkylaminocarbonyl, mono (optionally substituted phenyl or naphthyl) gone) aminocarbonyl, (aminocarbonyl (Cl-Cd) alkyl) aminocarbonyl, (amino (Cl- Cd) alkyl) aminocarbonyl, (hydroxy (Cl- Cd) alkyl) aminocarbonyl, hydroxyamidino, ureido, mono (Cl-Cd) alkylureido , optionally substituted mono- phenyl or naphthyl) ureido, mono- phenyl or optionally substituted naphthyl) (Cl-Cd) alkylureido,

(mono (C1-C8) alkyl) (mono (optionally substituted phenyl or naphthyl)) ureido, (halo (Cl-Cd) alkylcarbonyl) ureido, ureido (C1-C8) alkyl, mono (Cl-Cd) alkylureido (Cl-) Cd) alkyl, di (Cl-Cd) 'al-quilureido (Cl-Cd) alkyl, mono-phenyl or optionally substituted naphthyl) ureido (C1-.C8) alkyl, mono-phenyl or optionally substituted naphthyl) (Cl-Cd) alkylureido (C1 -C8) alkyl, monohalo (Cl-Cd) alkylureido (Cl-Cd) alkyl, (halo (Cl-Cd) alkyl) ((Cl-Cd) alkyl) -ureido (Cl-Cd) alkyl, ((Cl-Cd) ) alkoxycarbonyl (Cl-Cd) alkyl) ureido (Cl-C8) alkyl, glycinamide, mono (Cl-Cd) alkyl glycinamide, aminocarbonylglycinamide, ((Cl- Cd) alkoxy (Cl-Cd) alkylcarbonyl) glycinamide, (aminocarbonyl) ((C1-C8) alkyl) glycinamide, ((Cl-Cd) alkoxycarbonyl (Cl-Cd) alkylcarbonyl) ((Cl-Cd) alkyl) glycinamide, ((C1-C8) alkoxycarbonylamino (Cl- Cd) alkylcarbonyl) glycinamide, (phenyl or optionally substituted naphthyl) carbonylglycinamide, ((phenyl or optionally substituted naphthyl) do) carbonyl) ((C1-C8) alkyl) glycinamide, (mono (optionally substituted phenyl or naphthyl) (C1-C8) alkyl aminocarbonyl) ((Cl-Cd) alkyl) glycinamide, (mono-phenyl or optionally substituted naphthyl) minocarbonyl glycinamide, (mono- phenyl or optionally substituted naphthyl) aminocarbonyl) ((Cl-Cd) alkyl) glycinamide, alaninamide, 3- to 15-membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, and (3 to 15 membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (Cl-Cd) alkyl, d. The compound of claim 7 selected from the group consisting of the following compounds: 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) iperazine; 4 (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-ethylpiperazine; (21?) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-propylpiperazine; (25) -4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-propylpiperazine; 4- (4-fluorobenzyl) -1- (((4-chlorophenoxy) methyl) carbonyl) spiro [cyclopropan-1,2 '-piperazine]; 1- ((4-chlorophenoxy) methyl) carbonyl-2-hydroxymethyl-4- (4-fluorobenzyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (2- (methoxy) ethyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-2- (2- ((2-methylpropap) amino) ethyl) -4- (4-fluorobenzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-3-methyl-4- (4-fluorobenzyl) piperazine; - ((4-chlorophenoxy) methyl) carbonyl-4- (4-fluorobenzyl) -5-methylpiperazine; (2l?) - l- ((4-chlorophenoxy) methyl) carbonyl-3-methyl-4- (4-fluorobenzyl) piperazine; (2S) -l- ((4-chlorofinoxy) methyl) carbonyl-3-methyl-4- (4-fluorobenzyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (hydroxymethyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxyethyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (((methyl) ureido) methyl) piperazine; (21 ?, 31?) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2,3-dimethylpiperazine; (cis) -1- ((4-chlorophenoxy) methyl) carbonyl-3,5-dimethyl-4 - (4-fluorobenzyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (2- (((4-chlorophenoxy) methyl) carbonyl) oxy) -ethyl-5-methylpiperazine; (2 R, 51?) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5 ((hydroxy) methyl) piperazine; (21? 51?) -4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5- ((methoxy) -methyl) piperazine;

(21 ?, 55) -4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5- (1-methylethyl) piperazine; (21? 51?) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5- (1-hydroxyethyl) piperazine; (21? 51?) -4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5- (1-hydroxy? Rop-3-enyl) piperazine; '5 • (2l?, 5S) -l- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4'-fluorobenzyl) -5- ((cyano) methyl) piperazine; (21? 51?) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((1, 2,4-triazol-2-yl) methyl) piperazine; 0 (21?, 51?) - l- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((tetrazolyl) methyl) piperazine; (3S, 5S) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3,5-dimethylpiperazine; 1- ((4-chloro-3-nitrophenoxy) methyl) carbonyl-2-methyl-4-5 (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2-methylphenoxy) methyl) carbohyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((4-chloro-2- (diethylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2-hydroxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((5-chloro-2-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine;

(traε) -1- ((4-chloro-2- ((ethyl) (1-methylbutyl) aminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl ') piperazine; 1- ((4-chloro-2-aminophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; 1- ((4-chloro-3-nitrophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; - (trans) -1- ((4-chloro-2- (benzylamino) phenoxy) methyl) carbonyl-2,5-diraethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((1-methylbutyl) amino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; - (trans) -1- ((4-chloro-2- (iso-propylcarbonylamino) phenoxy) -ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) pipe'razine; (trans) -1- ((4-chloro-2- (N '- (2,4-dichlorophenyl) ureido) phenoxy) -ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N '- (4-nitrophenyl) ureido) phenoxy ") methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; trans) -1- ((4-chloro-2- (N '- (4-methylphenyl) ureido) phenoxy) methyl) carbonyl-2, 5-dlmethyl-4 ~ (4-fluorobenzyl) piperazine; (trans) .- 1- ((4-Chloro-2- (N '-benzylureido) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2) - ((cyclopropylmethyl) aminomethyl) phenoxy) butyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine- (trans) -1- ((4-chloro-2- (phenylaminomethyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (acetylaminomethyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((methylamino) (phenyl) methyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (1 ~ (phenylsulfonyl) (methyl) aminophenyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (tra ns) -1- ((4-chloro-2- (1- (acetyl) (methyl) aminoethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (1- (N-methyl-N'-ethylureido) ethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine;

(trans) -1- ((4-chloro-2- (1- ((methyl) (ethyl) amino) ethyl) phenoxy) methyl.) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (1- (dimethylamino) ethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (21?) - l- ((4-chloro-2- ((4-t-butoxycarbonylpiperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (rans) -1- ((4-chloro-2- ((piperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4- 'fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (oxazol-2-ylaminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) pyrrazine; 1- ((4-chloro-2- (morpholin-4-ylmethyl) phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((4-bromo-2-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; - (trans) -1- ((4-fluoro-3-chlorophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; 1- ((4-chloro-2-methoxycarbonylphenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine;

(trans) -1- ((4-chloro-2-methoxycarbonylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; 1- ((4-chloro-2-aminocarbonylphenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2-carboxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2-cyanophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l- ((3-cyanophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-methyl-2-aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (tra-ns) -1- ((3-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-Methyl-2-acetylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxycarbonylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluo-robenzyl) piperazine; (trans) -1- ((3-nitrophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-acetyl-2- (aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (-fluorobenzyl) piperazine; (trans) -1- ((4-nitro-3-phenylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((5-nitro-2-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-amino-3-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((5- nitro-2-aminophenoxy) methyl) carbonyl-2,5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-methoxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (rans) -1- ((4-methoxy-2-acetylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((5-Rethoxy-2-acetylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) 'piperazine; (trans) -1- ((2- ((2-hydroxyethyl) aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- ((2-hydroxyethoxy) carbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4- (fluorobenzyl) piperazine;

(trañs) -1- ((2- (2-hydroxyethoxy) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-Acetyl-4,5-dimethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((5-methoxy-2- (methoxycarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; 4- (4-fluorobenzyl) -! - ((4-chlorophenoxy) methyl) carbonyl- 2- (N '-methylureido) mino) methyl) piperazine; (rans) -1- ((4-methyl-2-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-chloro-5-methoxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4 ~ (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-5-nitrophenoxy) methyl) carbonyl-2,5-diraethyl-4- (4-fluorobenzyl) piperazine; (-trans) -1- ((2- (hydroxymethyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine '; (trans) -1- ((2-Rethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-2- (2-azidoethyl) -4- (4-fluorobenzyl) iperazine; (trans) -1- ((4-chloro-2- (phthalimido) phenoxy) methyl) carbonane-2,5-dimethyl-4- (4-fluorobenzyl) piperazine;

(trans) -1- ((4-chloro-2- (maleimido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-Chloro-2- ((4- (benzylcarbonyl) piperazin-1-yl) methyl) phenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-Chloro-2- ((4- ((2,3,4-trifluorophenyl) aminocarbonyl) piperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((4- ((2-fluorophenyl) aminocarbonyl) piperazin-1-yl) ethylene) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((N '- (2,6-difluorophenyl) ureido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; trans) -1- ((4-chloro-2- (ethenylcarbonylamino) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2) - (cyclopropylcarbonylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (cyclopentylcarbonylamino) phenoxy) methyl) carbonyl- 2,5-dimethyl-4- (4-fluorobenzyl) piperazine;

(trans) -1- ((4-chloro-2- ((furan-2-yl) carbonylamino) phen-xy) methyl) carbonyl-2,5-dimethyl-4- (fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (phenylcarbonylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (fluorobenzyl) piperazine; (trans) -l- ((4-chloro-2- ((N '- (methoxyphenyl) ureido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; 10 (trans) - 1- ((4-chloro-2- ((N'- (methoxycarbonylmethylcarbonyl) -N'- (methyl) guanyamido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-Chloro-2- ((N '- (2-methoxycarbonyl-15-ethyl) carbonylN' - (methyl) glycinamide) phenoxy) methy

- carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine (trans) -1- ((4-chloro-2- ((N '- (3-methylbenzyl) aminocar-' bonyl-N '~ ( methyl) glycinamide) phenoxy) methyl) ca bonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; 20 (trans) -l- ((4-chloro-2- ((N'- (3-trifluoromethyl) -4-fluorophenyl) carbonyl-N'- (methyl) glycinamide) f-noxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl piperazine;

(trans) -1- ((4-chloro-2- ((N '- (4-methylbenzyl) aminocarbonyl-N' - (methyl) glycinamide) phenoxy) methyl) carbonyl-2,5-dimethyl- 4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((N '- (3-chlorophenyl) carbonyl-N' - (methyl) glycinamide) phenoxy) methyl) carbonyl-2 , 5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((N '- (4-fluorobenzyl) aminocarbonyl-N' - (methyl) glycinamide) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N '- (2-iodophenylcarbonyl) glycinamide) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N '- (2,3-difluorophenylcarbonyl) glycinamide) phenoxy) -methyl) carbonyl-2, 5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-Clsro-2- (N '- ((4-phenoxyphenyl) aminocarbonyl) glycinamide) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N r- (2,4-diflurophenylcarbonyl) glycinamide) phenoxy) methyl) -carbonyl-2-, 5- dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((2-iodophenylcarbonyl) minomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((ethoxycarbonylmethylcarbonyl) aminomethyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N '- (3-chloropropyl) ureidomethyl) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N '- (2-fluoro-6-trifluoromethyl-phenyl) ureidomethyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) ) piperazine; (trans) -1- ((4-chloro-2- ((3-fluorophenyl) carbonylaminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N '- (2- (ethoxycarbonyl) ethyl) ureidomethyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; . . - "(25) -l- ((4-chloro-2- (ureido) phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro- 2- ((2,5-di (trifluoromethyl) phenyl) carbonylaminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; and (trans) -1- ((4- chloro-2- (N '- (2- (phenyl) cyclopropyl) ureidomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine 9. The compound of claim 7, wherein that: R la is one or more substituents selected from the group consisting of (Cl-Cd) alkyl and hydroxy (Cl-Cd) alkyl, R 2 is one or more substituents selected from the group consisting of hydrogen, chloro or R3 is phenyl substituted by one or more substituents selected from the group consisting of halo, (Cl-Cd) alkyl, (Cl-Cd) alkoxy, formyl, nitro, (C3-C10) cycloalkylamino (C1-C8) alkyl, hydroxy (Cl-5 C8) alkyl, amino, (Cl-Cd) -alkylcarbonylamino, halo (C1-C8) alkylcarbonylamino, (C1-C8) alkoxy (Cl - Cd) alkylcarbonylamino, (Cl-Cd) 'alkoxycarbonyl (Cl- Cd) alkylcarbonylamino, (Cl- Cd) alkylsulfonylamino, anaino (Cl-Cd) alkyl, mono (Cl-Cd) alkylamino (Cl-0 Cd) alkyl, di (Cl-Cd) alkylamino (Cl-Cd) alkyl,

((C1-C8) alkylsulfonyl) ((C1-C8) alkyl) amino (Cl-Cd) alkyl, (C1-C8) alkylcarbonyl, aminocarbonyl, mono (Cl-C8) alkylaminocarbonyl, mono-phenyl or optionally substituted naphthyl) aminocarbonyl, ( aminocarbonyl (Cl-Cd) alkyl) aminocarbonyl, (C 1 -C 8) alkyl) aminocarbonyl, hydroxyamidino, ureido, (halo (Cl-Cd) alkylcarbonyl) ureido, (C 1 -C 8) ureido alkyl, glycinamide, mono (Cl- C8) alkylglycinamide, aminocarbonylglycinamide, ((C1-C8) alkoxy (C1-C8) alkylcarbonyl) glycinamide, (aminocarbonyl) ((C1-C8) alkyl) glycinamide, ((Cl-Cd) alkoxycarbonylamino (Cl- Cd) alkylcarbonyl) glycinamide, alaninamide, and (3- to 15-membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur) (Cl-C8) alkyl. 10. The compound of claim 9 selected from the group consisting of the following compounds: (trans) -1- ((4-chloro-3-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) ) piperazine; (trans) -1- ((4-chloro-2- (hydroxymethyl) phenoxy) methyl) carbonane-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (21 ?, 55) -1- ((4-chloro-2- (aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (25, 5.1?) -1- ((4-bromo-3,5-dimethoxyphenoxy) methyl) carbonane-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (21 ?, 55) -l- ((3-hydroxy-5-methylphenoxy) methyl) carbhenyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (2 5, 51?) -1- ((4-nitro-3-formylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (2R) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; 4- (4-fluorobenzyl) -l- ((4-chlorophenoxy) methyl) car-bonyl-2- (2-hydroxyethyl) piperazine; (trans) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2,5-dimethylpiperazine; (21? 55) -4- (4-Fluorobenzyl) -l- (- (4-chlorophenoxy) methyl) carbonyl-2,5-dimethylpiperazine; (trans) -1- ((4-chloro-3,5-dimethoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine;

(21 ?, 55) -1- ((4-chloro-3,5-dimethoxyphenoxy) methyl) carbonane-2,5-dimethyl-4- (4-fluorobenzyl) piperazine;

(21 ?, 55) -4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (2-hydroxyethyl) -5-methylpiperazine;

(21? 61?) -4- (4-Fluorobenzyl) -! - ((4-chlorophenoxy) methyl) carbonyl-2,6-dimethylpiperazine; (trans) -1- ((4-chloro-2-methoxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; 1- ((4-chloro-2- (hydroxymethyl) phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (21 ?, 55) -1- ((4-Chloro-3- (hydroxymethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (1-hydroxyethyl) phenoxy) methyl •) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine;

(trans) -1- ((4-chloro-2- (aminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (ureidomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2-aminophenoxy) methyl) ca-rbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; 1- ((4-chloro-2- (acetylamino) phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (trans) -4- (4-fluorobenzyl) -1- ((2-acetylamino-4-chlorophenoxy) methyl) carbonyl-2,5-dimethylpiperazine; (trans) -1- ((4-chloro-2- (propylcarboniland.no) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine;

(trans) -1- ((4-chloro-2- (methoxymethylcarbonylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (2- (methoxycarbonyl) ethylcarbonylamino) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-Chloro-2- (2-ethoxycarbonyl) ethylcarbonyl-amino) phenoxy) methyl) carbonyl-2,5-diraethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (methylsulfonylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (bromomethylcarbonylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (21?) -1- ((4-Chloro-2- (glycinamido) phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((N'-methylglycinamido) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (( 4-chloro-2- (alaninamido) phenoxy) methyl) carbonane-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine;

(trans) -1- ((4-chloro-2- ((aminocarbonyl) glycinamide) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (aminocarbonyl) (methyl) glycinamide) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N'-ethyluredio) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (ethylcarbonylamino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine;

(trans) -1- ((4-chloro-2-amino-5-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine, dihydrochloride salt; (trans) -1- ((4-chloro-2- (((ethyl) amino) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (((diethyl) amino) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (((cyclopropyl) am-ino) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (((dimethyl) amino) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (((methyl) amino) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((amino) methyl) phenoxy) methyl) carbonane-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((4-methylpiperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((piperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (ethylaminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (1- (methylamino) ethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (1- (methylsulfonyl) (methyl) aminoethyl) phenoxy) methyl) carbonane-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (2l?) - l- ((4-chloro-2- ((piperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (21 ?, 55) -1- ((4-chloro-2- ((piperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((4-t-butoxycarbonylpiperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (imidazol-1-ylmethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (1- (imidazol-1-yl) ethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (triazol-1-ylmethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (tetrazol-1-ylmethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((morpholin-4-yl) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (21?) -1- (- (4-chloro-2-aminocarbonylphenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; 1- ((4-chloro-2-formylphenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (21? 55) -! - ((4-chloro-2-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (21?) -1- ((4-chloro-2-formylphenoxy) -ethyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (trans) -! - ((4-chloro-2- (methylaminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((aminocarbonylmethyl) aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4- (fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((2-aminoethyl) aminocarbonyl) phenoxy) methyl) carbon l-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((4-aminocarbonyl optionally substituted phenyl) aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (hydroxyamidino) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine;

(trans) -1- ((4-chloro-2-acetylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; 5 (trans) -1- ((4-chloro-2- ((N'- (trichloromethylcarbonyl) ureido) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N'- (methoxymethylcarbonyl) glycinamide) phenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-io-fluorobenzyl) piperazine; and (trans) -1- ((4-chloro-2- (N '- (ethoxycarbonylaminocarbonyl) glycinamide) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine 11. The compound of claim 9, wherein R2 5 is 4-fluoro and R3 is phenyl substituted at the 4-position with chlorine and at the 2-position by aminocarbonyl, ureido, or glycinamide, namely the compound selected from the group consisting of the following compounds: (21? 55) -1- ((4-chloro-2- (aminocarbo-0 nyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro ~ 2- (glycinamide) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine;

(21?) - 1- ((4-chloro-2- (ureido) phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (ureido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; '5 (21 ?, 5S) -1- ((4-chloro-2- (ureido) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; and (21 ?, 55) -1- ((4-chloro-2- (glycinamide) phenoxy) methyl) carbonane-2,5-dimethyl-4- (4-fluorobenzyl) piperazine. The compound of claim 9 wherein the most preferred compound is: (21?) -l - '((4-chloro-2- (ureido) phenoxy) methyl) carboni? -2- methyl-4- (4-fluorobenzyl) piperazine; 13. The compound of claim 3 wherein: R4 is -N (R7) -; R5 is methylene; R6 is 0 -C (0) ~; and R7 is selected from the group consisting of hydrogen, (Cl-Cd) alkyl, phenyl or optionally substituted naphthyl, (optionally substituted phenyl or naphthyl) (Cl-Cd) alkyl, (C1-C8). alkylcarbonyl, (Cl-Cd) alkylcarbonyl (Cl-Cd) alkyl, (optionally substituted phenyl- or naphthyl) (Cl-Cd) alkylcarbonyl, (optionally substituted phenyl or naphthyl) (Cl-C8) alkylcarbonyl (C1-C8) alkyl , aminocarbonyl, mono (Cl-Cd) alkylaminocarbonyl, di (C 1 -C 8) alkylaminocarbonyl, and (Cl-Cd) alkoxycarbonyl. The compound of claim 13 wherein:

one or more substituents selected from the group consisting of halo, (Cl-Cd) alkyl, (C3-C10) cycloalkyl, (C3-C10) cycloalkylamino (C1-C8) alkyl, halo (C1-C8) alkyl, hydroxy (C1 -C8) alkyl, hydroxy (C2-C8) alkenyl, hydroxy (C2-C8) alkynyl, (hydroxy) (phenyl or optionally substituted naphthyl) (Cl-Cd) alkyl, cyano (Cl-Cd) alkyl, halo (Cl-) Cd) alkylcarbonylamino (Cl-Cd) alkyl, (Cl-C8) alkoxy (C1-C8) alkyl, (phenyl or optionally substituted naphthyl) (C1-C8) alkoxy (Cl-Cd) alkyl, (C1-C8) alkylthio ( C1-C8) alkyl, hydroxy (Cl-C8) alkylthio (Cl-Cd) alkyl, amino (C1-C8) alkyl, mono (C1-C8) alkylamino (C1-C8) alkyl, di (Cl- C8) alkylamino ( C1-C8) alkyl, mono-phenyl or optionally substituted naphthyl) amino (C1-C8) alkyl, mono-phenyl or optionally substituted naphthyl) (Cl-Cd) alkylamino (C1-C8) alkyl, azido (C1-C8) alkyl, mono (C1) -C8) alkylureide (Cl-Cd) alkyl, ((Cl-Cd) alkoxycarbonyl (Cl-Cd) alkyl) ureido (C1-C8) alkyl, hydroxy (Cl-Cd) alkylamino (C1-C8) alkyl, (optionally substituted phenyl or naphthyl) oxy (Cl-C8) alkylcarbonyloxy (Cl-Cd) alkyl, (optionally substituted phenyl or naphthyl) (C1-C8) alkoxy (Cl-Cd) alkylcarbonyloxy ( Cl-Cd) alkyl, (Cl-Cd) alkylcarbonyl (C 1 -C 8) alkyl, (Cl-Cd) alkoxycarbonyl, (Cl-Cd) alkoxycarbonyl (Cl-Cd) alkyl, and (heterocyclic from 3 to 15 members which consists of carbon atoms and between one and five heteróatomos selected from the group of nitrogen, oxygen and sulfur) (Cl- Cd) alkyl; R2 is one or more substituents selected from the group consisting of hydrogen and halo; R3 is phenyl which is optionally substituted by one or more substituents selected from the group consisting of hydrogen, hydroxy, halo, (Cl-Cd) alkyl, (Cl-C8) alkoxy, hydroxy (Cl-Cd) alkoxy, halo (C1) -C8) alkyl, formyl, nitro, cyano, amino (Cl-Cd) alkoxy, (C3-C10) cycloalkyl, (C3-C10) cycloalkylamino (Cl-C8) alkyl, (optionally substituted phenyl or naphthyl) (Cl-Cd) alkyl, hydroxy (C1-C8) alkyl, (mono (Cl-Cd) alkylamino) (optionally substituted phenyl or naphthyl) (C1-C8) alkyl, (Cl-Cd) alkoxy (Cl- Cd) alkyl, amino , mono (C1-C8) alkylamino, di (Cl-Cd) alkylamino, mono (phenyl or optionally substituted naphthyl) (Cl-Cd) alkylamino, (Cl-Cd) alkylcarbonylamino, (C2-C8) alkenylcarbonylamino, (C3-C10) cycloalkylcarbonylamino, (optionally substituted phenyl or naphthyl) carbonylamino, (3- to 15-membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms selected from the group of nitrogen, oxygen and sulfur) carbonyl no, halo (Cl-Cd) alkylcarbonylamino, (Cl-Cd) alkoxy (Cl-Cd) alkylcarbonylamino, (C 1 -C 8) alkoxycarbonyl (C 1 -C 8) alkylcarbonylamino, ((Cl-Cd) alkylcarbonyl) ((C 1 -C 8) alkyl) amino, (Cl-Cd) alkylsulfonylamino, amino (C1-C8) alkyl, mono (Cl-Cd) alkylamino (C1-C8) alkyl, di (Cl- Cd) alkylamino (Cl-Cd) alkyl, mono (optionally substituted phenyl- or naphthyl) amino (C 1 -C 8) alkyl, mono (phenyl or optionally substituted naphthyl) (Cl-C8) alkylamino (C 1 -C 8) alkyl, (C 1 -C 8) alkylca-r-phenylamino (C1) -C8) alkyl, (optionally substituted phenyl or naphthyl) carbonylamino-o (Cl-Cd) alkyl, ((Cl-Cd) alkylcarbonyl) ((Cl-Cd) alkyl) amino (Cl-Cd) alkyl, (cycloalkyl (Cl -Cd) alkyl) ami or (Cl-Cd) alkyl, (Cl-Cd) alkoxycarbonylamino (C1-C6) alkyl,

(Cl-Cd) alkoxycarbonyl (Cl-Cd) alkylcarbonylamino (C 1 -C 8) alkyl, ((C 1 -C 8) alkoxycarbonyl) ((Cl-Cd) alkyl) amino (C 1 -C 8) alkyl, (C 1 -C 8) alkylsulfonylamino ( C1-C8) alkyl, ((C1-C8) alkylsul-fonyl) ((Cl-Cd) alkyl) amino (Cl-Cd) alkyl, (optionally substituted phenyl or naphthyl) sulfonylamino (Cl-Cd) alkyl, ((phenyl or optionally substituted naphthyl) sulfonyl) ((C 1 -C 8) alkyl) amino (C 1 -C 8) alkyl, (3 to 15 membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms selected from the nitrogen group, oxygen and sulfur) amino (C1-C8) alkyl, carboxy, (C1-C8) alkoxycarbonyl, (C1-C8) alkylcarbonyl, (hydroxy (Cl-Cd) alkoxy) carbonyl, aminocarbonyl, mono (Cl-C8) alkylaminocarbonyl, mono-phenyl or optionally substituted naphthyl) aminocarbonyl, ((C 1 -C 8) alkyl) aminocarbonyl amino ((C 1 -C 8) amino) aminocarbonyl (hydroxy (C 1 -C 8) alkyl) aminocarbonyl, di (Cl-Cd) alkylaminocarbonyl ( C1-C8) alkyl, hydrox iamidino, ureido, mono (C1-C8) alkylureido, mono (phenyl or optionally substituted naphthyl) ureido, mono or phenyl. optionally substituted naphthyl) (C1-C8) alkylureido, (mono (Cl-Cd) alkyl) (mono-phenyl or optionally-substituted naphthyl)) ureido, (halo (C1-C8) alkylcarbonyl) ureido, ureido (Cl-Cd) alkyl, mono (Cl-C8) alkylureido (C1-G8) alkyl, di (Cl-Cd) alkyl (C1-C8) alkyl, optionally substituted mono-phenyl or naphthyl) ureido (C1-C8-) alkyl, mono-phenyl or naphthyl optionally substituted) (C1-C8) alkylureido (C1-C8) alkyl, monohalo (Cl-Cd) alkylureido (C1-C8) alkyl, (halo (C1-C8) alkyl) ((C1-C8) alkyl) ureido (Cl- Cd) alkyl, ((Cl-Cd) alkoxycarbonyl (Cl-Cd) alkyl) ureido (Cl-Cd) alkyl, glycine-mido, mono (Cl-Cd) alkylglycinamide, aminocarbonyl-glycinamide, ((Cl-Cd) alkoxy ( C1-C8) alkylcarbonyl) glycinamide, (aminocarbonyl) ((Cl-Cd) alkyl) glycine-mido, ((C1-C8) alkoxycarbonyl (C1-C8) alkylcarbonyl ') ((Cl-Cd) alkyl) glycinamide, (( C1-C8) alkoxycarbonylamino (C1-C8) alkylcarbonyl) glycinamide, (phenyl or optionally substituted naphthyl) carbo N-glycinamide, ((optionally substituted phenyl or naphthyl) carbonyl) ((Cl-Cd) alkyl) glycinamide, (mono- phenyl or optionally substituted naphthyl) (Cl-Cd) alkylaminocarbonyl) glycinamide, (mono- phenyl or optionally substituted naphthyl) (Cl-) Cd) alkylaminocarbonyl) ((Cl-Cd) alkyl) glycinamide, (mono (optionally substituted phenylene or naphthyl) aminocarbonyl) glycinamide, (mono- phenyl or optionally substituted naphthyl) aminocarbonyl) ((Cl-Cd) alkyl) glycinamide, alaninamide, heterocyclyl 3 to 15 members consisting of carbon atoms and between one and five heteróatomos selected from the group of nitrogen, oxygen and sulfur, and (heterocyclyl of 3 to 15 members consisting of carbon atoms and between one and five heteróatomos selected from the group of nitrogen, oxygen and sulfur) (C1-C8) alkyl. 15. The compound of claim 14 in which; one or more substituents selected from the group consisting of (Cl-C8) alkyl, - (C3-Cl0) cycloalkyl, hydroxy (Cl-Cd) alkyl, hydroxy (C2-Cd) alkenyl, cyano (Cl-C) alkyl , (C1-C8) (C1-C8) alkoxy alkyl, mono (C1-C8) alkylamino (C1-C8) alkyl, azido (C1-C8) alkyl, mono (C1-C8) alkylureido (Cl-Cd) alkyl, (optionally substituted phenyl or naphthyl) oxy (Cl-Cd) alkylcarbonyloxy (Cl-Cd) alkyl, and (3 to 15 membered heterocyclyl consisting of carbon atoms and between one to five heteroatoms selected from the nitrogen group, oxygen and sulfur) (Cl-Cd) alkyl; R2 is one or more - substituents selected from the group consisting of hydrogen, chlorine or fluoro; R3 is phenyl substituted by one or more substituents selected from the group consisting of hydroxy, halo, (Cl-Cd) alkyl, (Cl-Cd) alkoxy, formyl, nitro, cyano, amino (Cl-Cd) alkoxy, ( C3-C10) cycloalkylamino (Cl-Cd) alkyl, hydroxy (C1-C8) alkyl, (mono (C1-C8) alkylamino) (phenyl or optionally substituted naphthyl) (cl-Cd) alkyl, (Cl- Cd) (C1-C8) alkoxy alkyl, amino, mono (C1-C8) alkylamino, di (C1-C8) alkylamino, mono (phenyl or optionally substituted naphthyl) (cl- C8) alkylamino,

(C1-C8) alkylcarbonylamino, (C2-C8) alkenyl-carbonylamino, (C3-C10) cycloalkylcarbonylamino, (optionally substituted phenyl or naphthyl) carbonylamino, (3- to 15-membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms selected from the group of nitrogen, oxygen and sulfur) carbonylamino, halo (Cl-Cd) alkylcarbonylamino, (C 1 -C 8) alkoxy (C 1 -C 8) alkylcarbonylamino, (C 1 -C 8) alkoxycarbonyl (C 1 -C 8) alkylcarbonylamino, (Cl-Cd) alkylsulfonylamino, amino (Cl-Cd) alkyl, mono (Cl- Cd) alkylamino (Cl-Cd) alkyl, di (Cl-Cd) alkylamino (Cl-Cd) alkyl, mono (phenyl- or naphthyl optionally substituted) (Cl-C8) alkylamino (C1-C8) alkyl, (C1-C8) alkylcar-bonylamino (Cl-Cd) alkyl, (optionally substituted phenyl or naphthyl) carbonylamino (Cl-Cd) alkyl, ((Cl-Cd) alkylcarbonyl) ((Cl-Cd) alkyl) amino (Cl-Cd) alkyl, (cycloalkyl (Cl-Cd) alkyl) amino (Cl-C8) alkyl, (C1-C8) alkoxycarbonyl (Cl-C8) alkylcarbonylamino (C1 -C8) alkyl, (C1-C8) alkylsulfonylamino (Cl-Cd) alkyl, ((Cl-C8) alkylsulfonyl) ((Cl-Cd) alkyl) amino (Cl-Cd) alkyl, - (optionally substituted phenyl or naphthyl) sulfonylamino (C1-) C8) alkyl, ((optionally substituted phenyl or naphthyl) sulfonyl) ((Cl-Cd) alkyl) amino (Cl-Cd) alkyl, carboxy, (Cl- Cd) alkoxycarbonyl, (Cl-Cd) alkylcarbonyl, (hydroxy) (C1-C8) alkoxycarbonyl, aminocarbonyl ,. mono (Cl-Cd) alkylaminocarbonyl, mono (optionally substituted phenyl or naphthyl) aminocarbonyl, (aminocarbonyl (Cl-Cd) alkyl) aminocarbonyl, (amino (C 1 -C 8) alkyl) aminocarbonyl, (hydroxy (C 1 -C 8) al quil) amino-carbonyl, hydroxyamidino, ureido, mono (Cl-C8) alkylureido, mono-phenyl or optionally substituted naphthyl) ureido, mono-phenyl or optionally substituted naphthyl) (Cl-Cd) alkylureido, (mono (Cl-Cd) alkyl) ( mono (phenyl or naphthyl optionally substituted)), (halo (C 1 -C 8) alkylcarbonyl) ureido, (C 1 -C 8) ureido alkyl, mono (C 1 -C 8) alkylureido (Cl-Cd) alkyl, di (Cl-) Cd) alkylureido (Cl-Cd) alkyl, mono (optionally substituted phenyl or naphthyl) ureido (Cl-Cd) alkyl, mono (phenyl or optionally substituted naphthyl) (C 1 -C 8) alkylureido (Cl-Cd) alkyl, monohalo (Cl) -Cd) alkylureido (C1-C8) alkyl, (halo (Cl- Cd) alkyl) ((Cl- Cd) alkyl) ureido (Cl-Cd) alkyl, ((Cl- C8) alkoxycarbonyl (C1-C8) alkyl) ureido (Cl-C8) alkyl, glycinamide, mono ( C1-C8) alkylglycinamide, aminocarbonylglycinamide, ((Cl-C8) alkoxy (C1-C8) alkylcarbonyl) glycinamide, (aminocarbonyl) ((C1-C8) alkyl) glycinamide, ((Cl-Cd) alkoxycarbonyl) (Cl-Cd) alkylcarbonyl) ((C 1 -C 8) alkyl) glycinamide, ((C 1 -C 8) alkoxycarbonylamino (Cl-Cd) alkylcarbonyl) glycinamide, (optionally substituted phenyl or naphthyl) carbonylglycinamide, ((fe-nyl or naphthyl optionally substituted) carbonyl) ((Cl-Cd) alkyl) glycinamide, (optionally substituted mono- phenyl or naphthyl) (cl-C8) alkylaminocarbonyl) ((Cl-C) alkyl) glycinamide, (mono- phenyl or optionally substituted naphthyl) aminocarbonyl) glycinamide , (mono (optionally substituted phenyl or naphthyl) aminocarbonyl) ((C 1 -C 8) alkyl) glycinamide, alaninamide, 3 to 15 membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms selected from the group of nitrogen, oxygen and sulfur, and (3- to 15-membered heterocyclyl consisting of carbon atoms and between a or and five heteróatomos selected from the group of nitrogen, oxygen and sulfur) (Cl-Cd) alkyl. 16. The compound of claim 15 wherein:

one or more substituents selected from the group consisting of (Cl-Cd) alkyl and hydroxy (Cl-Cd) alkyl; R 2 is one or more substituents selected from the group consisting of hydrogen, chloro or fluoro; R3 is phenyl substituted by one or more substituents selected from the group consisting of halo, (Cl-C8) alkyl, (Cl-Cd) alkoxy, formyl, nitro, (3C-CIO) cycloalkylamino (C1-C8) alkyl, hydroxy ( Cl- C8) alkyl, amino, (C1-C8) alkylcarbonylamino, halo (C1-C8) alkylcarbonylamino, (Cl-Cd) alkoxy (Cl-Cd) alkylcarbonylamino, (Cl-Cd) alkoxycarbonyl (Cl- - Cd) alkylcarbonylamino, (C1-C8) alkyl-sulfonylamino, amino (Cl-Cd) alkyl, mono (Cl-Cd) alkylamino (Cl-Cd) alkyl, di (Cl-Cd) alkylamino (Cl-Cd) alkyl ,. . . ((Cl-Cd) alkylsulfonyl) ((C 1 -C 8) alkyl) amino (Cl-5 Cd) alkyl,. (Cl-Cd) alkylcarbonyl, aminocarbonyl, mono (Cl-Cd) alkylaminocarbonyl, mono (optionally substituted phenyl or naphthyl) aminocarbonyl, ((C 1 -C 8) aminocarbonyl) aminocarbonyl, (amino (C 1 -C 8) alkyl) aminocarbonyl, hydroxyamidino , Ureido, (halo (C1-C8) alkylcarbonyl) ureido, ureido (Cl-Cd) alkyl, glycinamide, mono (Cl- Cd) alkylglycinamide, aminocarbonylglycinamide, ((Cl-Cd) alkoxy (Cl-Cd) alkylcarbonyl) glycinamide , (aminocarbonyl) ((Cl-Cd) alkyl) glycinamide, ((Cl-15 Cd) alkoxycarbonylamino (Cl- Cd) alkylcarbonyl) glycinamide, alaninamide, and- (3 to 15-membered heterocyclyl consisting of carbon atoms) and between one and five heteróatomos selected from the group of nitrogen, oxygen and sulfur) (C1-C8) alkyl. 17. The compound of claim 16 wherein R 2 is 4-fluoro and R 3 is phenyl substituted at the 4-position with chlorine and optionally substituted at the 2-position with aminocarbonyl, ureido, or glycinamide.

ld. The compound of claim 17 selected from the group consisting of the following compounds: (rans) -1- ((4-chlorophenylamino) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; 1- ((4-chloro-2- (aminocarbonyl) phenylamino) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; and 1- ((4-chlorophenylamino) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine. 19. The compound of claim 3 wherein: R4 is -C (R8) 2- r R5 is methylene; R 6 'is -C (O) -; and each R8 is selected from the group consisting of hydrogen, (Cl-Cd) alkyl, amino, mono (C1-C8) alkylamino, di (C1-C8) alkylamino, (C1-C8) alkylcarbonylamino, (C3-C10) cycloalkylcarbonylamino, - (C3-C10) cycloalkyl (C1-C8) alkylcarbonylamino, (C1-C8) alkoxycarbonylamino, (C1-C8) alkyl- -sulfonylamino, (phenyl or optionally substituted naphthyl) carbonylamino, ( C1-C8) alkoxycarbonyl (Cl- Cd) alkylcarbonylamino, (Cl-Cd) alkylcarbonylamino (Cl-Cd) alkyl, (C3-C10) cycloalkylcarbonylamino (Cl-Cd) alkyl, (Cl-Cd) alkoxycarbonylamino (Cl-Cd) ) alkyl, (3- to 15-membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylamino (Cl-Cd) alkyl, (optionally substituted phenyl or naphthyl) sulfonylamino, (Cl- Cd) alkylsulfonylamino (Cl-Cd) alkyl, ureido, mono (Cl-Cd) alkylureido, monohalo (Cl-Cd) alkylureido, ureido (C1-C8) alkyl, mo no (Cl-Cd) alkyl (C 1 -C 8) alkyl, monohalo (Cl-Cd) alkylureido (C 1 -C 8) alkyl, amino (Cl-Cd) alkyl, mono (C 1 -C 8) alkylamino (C 1 -C 8) alkyl, and di (Cl-Cd) alkylamino (Cl-C8) alkyl. 'twenty. The compound of claim 19 wherein: Rla is one or more substituents selected from the group consisting of halo, (Cl-Cd) alkyl, (C3-C10) cycloalkyl, (C3-C10) cycloalkylamino (C1-C8) ) alkyl, halo (Cl-Cd) alkyl, hydroxy (C1-C8) alkyl, hydroxy (C2-C8) alkenyl, hydroxy (C2-C8) alkynyl, (hydroxy) (phenyl or optionally substituted naphthyl) (Cl-) Cd) alkyl, cyano (C1-C8) alkyl, halo (Cl-Cd) alkylcarbonylamino (C1-C8) alkyl, (Cl-Cd) alkoxy (Cl-Cd) alkyl, (phenyl or optionally substituted naphthyl) (Cl-Cd) ) (C1-C8) alkoxy alkyl, (Cl-Cd) alkylthio (Cl-Cd) alkyl, hydroxy (Cl-C8) alkylthio (C1-C8) alkyl, amino (Cl-Cd) alkyl, mono (C1-C8) (C 1 -C 8) alkylamino, di (Cl-Cd) alkylamino (Cl-Cd) alkyl, mono-phenyl or optionally substituted naphthyl) amino (Cl-Cd) alkyl, mono-phenyl or optionally substituted naphthyl) (Cl-Cd) alkylamino (Cl) -Cd) alkyl, azido (C1-C8) alkyl, mono (Cl-Cd) alkylureido (Cl-Cd) alkyl, ((Cl- Cd) alkoxy) carbonyl (Cl-Cd) alkyl) ureido (Cl- Cd) alkyl, hydroxy (Cl- Cd) alkylamino (Cl- 'Cd) alkyl, (optionally substituted phenyl or naphthyl) oxy (Cl- Cd) alkylcarbonyloxy (C1-) C8) alkyl, (optionally substituted phenyl or naphthyl) (Cl- Cd) alkoxy (Cl-Cd) alkylcarbonyloxy (C1-C8) alkyl, (C1-C8) alkylcarbonyl (C1-C8) alkyl, (Cl-Cd) al- coxycarbonyl, (C1-C8) alkoxycarbonyl (Cl- Cd) alkyl, - and (3- to 15-membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms selected, from the group consisting of nitrogen, oxygen and sulfur) (Cl -Cd) alkyl; R 2 is one or more substituents selected from the group consisting of hydrogen and halo; R3 is phenyl which is optionally substituted by one or more substituents selected from the group consisting of hydrogen, hydroxy, halo, (Cl-Cd) alkyl, (Cl- Cd) alkoxy, hydroxy (C1-C8) alkoxy, halo (Cl-) Cd) alkyl, formyl, nitro, cyano, amino (Cl-Cd) alkoxy, (C3-C10) cycloalkyl, (C3-C10) cycloalkylamino (Cl-Cd) alkyl, (optionally substituted phenyl or naphthyl) (Cl-Cd) alkyl, hydroxy (C 1 -C 8) alkyl, (mono (Cl-Cd) alkylamino) (phenyl or optionally substituted naphthyl) (Cl-Cd) alkyl, (Cl-Cd) alkoxy (Cl-Cd) alkyl, amino, mono ( C1-C8) alkylamino, di (C1-C8) alkylamino, mono-phenyl or optionally substituted naphthyl) (Cl-Cd) alkylamino(C1-C8) alkylcarbonylamino, (C2-Cd) alkenylcarbonylamino, (C3-C10) cycloalkylcarbonylamino, (optionally substituted phenyl or naphthyl) carbonylamino, (3- to 15-membered heterocyclyl consisting of carbon atoms, and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylamino, halo (C1-C8) alkylcarbonylamino, (Cl- Cd) alkoxy (C1-C8) alkylcarbonylamino, (Cl-Cd) alkoxycarbonyl (C1-C8) alkylcarbonylamino, ((Cl-Cd) alkylcarbonyl) '((C 1 -C 8)' alkyl) amino, (Cl-Cd) alkylsulfonylamino, amino (Cl-Cd) alkyl, mono (Cl-Cd) alkylamino (C 1 -C 8) alkyl , di (Cl-Cd) alkylamino (Cl-Cd) alkyl, mono (phenyl or optionally substituted naphthyl) amino (Cl-Cd) alkyl, mono (optionally substituted phenyl or naphthyl) _ (Cl-Cd) alkylamino (Cl -Cd) alkyl, (Cl-Cd) alkylcarbonylamino (Cl-Cd) alkyl, (optionally substituted phenyl or naphthyl) carbonylamino (Cl-Cd) alkyl ,. ((Cl-Cd) alkylcarbonyl) ((C 1 -C 8) alkyl) amino (Cl-Cd) alkyl, (cycloalkyl (Cl-Cd) alkyl) amino (Cl-Cd) alkyl, (Cl-Cd) alkoxycarbonylamino (Cl-) C8) alkyl, - (C1-C8) alkoxycarbonyl (C1-C8) alkylcarbonylamino (Cl-Cd) alkyl, ((Cl-Cd) alkoxycarbonyl) ((C1-C8) alkyl) amino (Cl-Cd) alkyl, . (Cl-Cd) alkylsulfonylamino (Cl-Cd) alkyl, ((Cl-Cd) alkylsulfonyl) ((Cl-Cd) alkyl) amino (C 1 -C 8) alkyl, (optionally substituted phenyl or phthaphthyl) sulphonylamino (C 1 -) C8) alkyl, ((optionally substituted phenyl or naphthyl) sulfonyl) ((Cl-Cd) alkyl) amino (Cl-Cd) alkyl, (3 to 15 membered heterocyclyl consisting of carbon atoms and between one and 'five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) amino (Cl-Cd) alkyl, carboxy, (C1-C8) alkoxycarbonyl, (Cl-Cd) alkylcarbonyl, (hydroxy (Cl-Cd) alkoxy) carbonyl, aminocarbonyl, mono ( Cl-Cd) alkylaminocarbonyl, mono (optionally substituted phenyl or naphthyl) aminocarbonyl, (aminocarbonyl (Cl-Cd) alkyl) aminocarbonyl, (amino (Cl-Cd) alkyl) aminocarbonyl, (hydroxy (Cl-Cd) alkyl) aminocarbonyl, di (Cl-Cd) alkylaminocarbonyl (Cl-Cd) alkyl, hydroxyamidino, ureido, mono (Cl-C8) alkylureido, o-no (phenyl or optionally substituted naphthyl) ureido, mono (phenyl or naphthyl) optionally substituted) (Cl-Cd) alkylureido, (mono (Cl-Cd) alkyl) (mono (optionally substituted phenyl or naphthyl)) ureido, (halo (Cl- Cd) alkylcarbonyl) ureido, ureido (Cl-Cd) alkyl, mono (Cl-Cd) alkylureido (Cl-Cd) alkyl, di (Cl- Cd) alkylureido (C 1 -C 8) alkyl, mono- phenyl or optionally substituted naphthyl) ureido (C 1 -C 8) alkyl, monophenyl or optionally substituted naphthyl) (Cl- Cd) alkylureido (Cl-Cd) alkyl, monohalo (Cl- Cd) alkylureido (C1-C8) alkyl, '(halo (Cl- Cd) alkyl) ((Cl-Cd) alkyl) ureido (Cl-Cd) ) alkyl, ((Cl- Cd) alkoxycarbonyl (Cl-Cd) alkyl) ureido (C1-C8) alkyl, glycinamide, mono (C1-C8) alkylglycinate, aminocarbonylglycinamido, ((C1-C8) alkoxy (Cl-Cd) alkylcarbonyl) glycinamide, (aminocarbonyl) ((Cl-Cd) alkyl) glycinamide, ((C 1 -C 8) alkoxycarbonyl (Cl-Cd) alkylcarbonyl) ((C 1 -C 8) alkyl) glycinamide, ((Cl-Cd) alkoxycarbonylamirium ( Cl-Cd) alkylcarbonyl) glycine-- (optionally substituted phenyl or naphthyl) carbonate glycinamide, ((phenyl or optionally substituted naphthyl) carbonyl) ((Cl-Cd) alkyl) glycinamide, (mono- phenyl or optionally substituted naphthyl) (Cl- Cd) alkylaminocarbonyl) glycinamide, (mono- phenyl or optionally substituted naphthyl) (Cl- Cd) alkylaminocarbonyl) ((Cl-Cd) alkyl) glycinamide, (mono- phenyl or optionally substituted naphthyl) aminocarbonyl) glycinamide, (mono- phenyl or optionally substituted naphthyl) aminocarbonyl) ((Cl- Cd) alkyl) glycinamide, alaninamido, heterocyclyl 3 to 15 members consisting of carbon atoms and between one and five selected heteroatoms. from the group consisting of nitrogen, oxygen and sulfur and (3- 15membered heterocyclyl which consists of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (Cl- Cd) alkyl. twenty-one.' The compound of claim 20 wherein:

one or more substituents selected from the group. po formed by (Cl-Cd) alkyl, (C3-C10) cycloalkyl, hydroxy (Cl-Cd) alkyl, hydroxy (C2 ~ Cd) alkenyl, cyano (Cl-Cd) alkyl, (Cl- Cd) alkoxy (Cl-) Cd) alkyl, mono (Cl-Cd) alkylamino (Cl-Cd) alkyl, azido (Cl-Cd) alkyl, mono (Cl-Cd) alkyleneide (Cl-Cd) alkyl, (optionally substituted phenyl or naphthyl) oxy (Cl-Cd) alkylcarbonyloxy (Cl- Cd) alkyl, and (3- 15 membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (C 1 -C 8) alkyl; R2 is one or more substituents selected from the group consisting of hydrogen, chlorine or fluoro; R3 is phenyl substituted by one or more substituents selected from the group consisting of hydroxy, halo, (C1-C8) alkyl, (Cl-Cd) alkoxy, formyl, nitro, cyano, amino (Cl-Cd) alkoxy, (C3-C10) cycloalkylamino (Cl-Cd) alkyl, hydroxy (Cl-Cd) alkyl, (mono (Cl-Cd) alkylamino) (phenyl or optionally substituted naphtyl) (Cl-Cd) 'alkyl, (Cl-Cd) alkoxy (Cl- Cd) alkyl, amino, mono (Cl-Cd) alkylamino, di (Cl- 1.

5 Cd) alkylamino, mono (phenyl or optionally substituted naphthyl) (Cl-Cd) alkylamino, (Cl-Cd) alkylcarbonylamino, ( C2-C8) alkenylcarbonylanu.no, (C3-C10) cycloalkylcarbonylamino, (optionally substituted phenyl or naphthyl) carbonylamino, (3 to 15 membered heterocyclic group consisting of carbon atoms and between one and five heteroatoms selected from the group formed by nitrogen, oxygen and sulfur) carbonylamino, halo (Cl- C8) alkylcarbonylamino, (Cl-Cd) alkoxy (Cl- Cd) alkylcarbonylamino, (C 1 -C 8) alkoxycarbonyl (Cl- Cd) alkylcarbonylamino, (Cl-Cd) ) alkylsulfonylamino, amino (Cl-Cd) alkyl, mono (Cl-C8) alkyl-amino (Cl-Cd) alkyl, di (Cl-Cd) alkylamino (-C1- C8) alkyl, mono (phenyl or optionally substituted naphthyl) (C1-C8) (C1-C8) alkylamino alkyl, (Cl-Cd) alkylcarbonylamino (C1-C8) alkyl, (optionally substituted phenyl or naphthyl) carbonylamino (Cl-C8) alkyl, ((C1-C8) alkylcarbonyl) ( (Cl-C8) alkyl) amino (Cl-Cd) alkyl, (cycloalkyl (Cl-Cd) alkyl) amino (Cl-Cd) alkyl, (C1-C8) alkoxycarbonyl (Cl-Cd) alkylcarbonylamino (C1-C8) alkyl , (Cl-Cd) alkylsulfonylamino (C1-C8) alkyl, ((Cl-C8) alkylsulfonyl) '((C1-C8) alkyl) amino (Cl-Cd) alkyl, (optionally substituted phenyl or naphthyl) sulfonylamino (Cl-) Cd) alkyl, ((optionally substituted phenyl or naphthyl) sulfonyl) ((Cl-Cd) alkyl) amino (Cl-Cd) alkyl, carboxy, (Cl-Cd) alkoxycarbonyl, (C 1 -C 8) alkylcarbonyl, (hydroxy (Cl -Cd) alkoxycarbonyl, aminocarbonyl, mono (C1-C8) alkylaminocarbonyl, mono (phenyl or naphthyl optionally substituted) aminocarbonyl, (aminocarbonyl (Cl-Cd) alkyl) aminocarbonyl; (amino (Cl-Cd) alkyl) aminocarbonyl, (hydroxy (Cl-Cd) alkyl) aminocarbonyl, hydroxyamidino, ureido, mono (C1-C8) alkylureido, mono-phenyl or optionally substituted naphthyl) ureido, mono (phenyl or naphthyl optionally substituted) (Cl-Cd) alkylureido, (mono (Cl-Cd) alkyl) (mono (optionally substituted phenyl or naphthyl)) ureido, (halo (Cl-Cd) alkylcarbonyl) ureido, ureido (Cl-Cd) alkyl, mono (Cl-Cd) al-quilureido (Cl-Cd) alkyl, di (Cl-Cd) alkylureido (C 1 -C 8) alkyl, mono-phenyl or optionally substituted naphthyl) ureido (Cl-Cd) alkyl, mono (optionally substituted phenyl or naphthyl) (Cl-Cd) alkylureido (Cl-Cd) alkyl, "monohalo (Cl-Cd) alkylureido (Cl-Cd) alkyl, '(halo (Cl- Cd) alkyl) ((Cl-Cd) alkyl)" ureido ( Cl-Cd) alkyl, ((C1-C8) alkoxycarbonyl (C1-C8) alkyl) ureido (Cl-Cd) alkyl, glycinamide, mono (C1-C8) alkylglyc-namido, aminocarbonylglycinamido, ((Cl-C8) al- coxi (C1-C8) alkylcarbo-nyl) glycinamide, (aminocarbonyl) ((Cl-Cd) alkyl) glycine amido, ((Cl-Cd) alkoxycarbonyl (Cl-Cd) alkylcarbonyl) ((C 1 -C 8) alkyl) glycinamide, ((C 1 -C 8) alkoxycarbonylamino (Cl-Cd) alkylcarbonyl) glycinamide, (phenyl or optionally substituted naphthyl) ) carbonylglycinamide, ((optionally substituted phenyl or naphthyl) carbonyl) ((Cl- Cd) alkyl) glycinamide, (mono- phenyl or optionally substituted naphthyl) (Cl-Cd) alkylaminocarbonyl)

(. (Cl-Cd) alkyl) glycinamide, (mono (optionally substituted phenyl or naphthyl) aminocarbonyl) glycinamide, (mono (optionally substituted phenyl or naphthyl) aminocarbonyl) ((C 1 -C 8) alkyl) glycinamide, alaninamide, 3- to 15-membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and (3- to 15-membered heterocyclyl consisting of carbon atoms and between one and five heteroatoms) selected from the group consisting of nitrogen, oxygen and sulfur) (C1-C8) alkyl. 22. The compound of claim 21 wherein: Rla is one or more substituents selected from the group consisting of (C1-C8) alkyl and hydroxy (Cl-Cd) alkyl; R2 is one or more substituents selected from the group consisting of hydrogen, chloro or fluoro; R3 is. phenyl substituted by one or more substituents selected from the group consisting of halo, (Cl-Cd) alkyl, (Cl-Cd) alkoxy, formyl, nitro, (C3-C10) cycloalkylamino (Cl-Cd) alkyl, hydroxy ( Cl- Cd) alkyl, amino, (Cl-Cd) alkylcarbonylamino, halo (Cl-Cd) alkylcarbonylamino, (Cl-Cd) alkoxy (Cl- Cd) alkylcarbonylamino, (C 1 -C 8) alkoxycarbonyl (Cl- Cd) alkylcarbonylamino, - (Cl- Cd) alkylsulfonylamino, amino (Cl-Cd) alkyl, mono (Cl-Cd) alkylamino (Cl-Cd) alkyl, di (Cl- Cd) alkylamino (Cl-Cd) alkyl, ((Cl-Cd) alkylsulphonyl) ((Cl-Cd) alkyl) amino (Cl-Cd) alkyl, (Cl- Cd) alkylcarbonyl, aminocarbonyl, mono (Cl- Cd) alkylaminocarbonyl, mono- phenyl or optionally substituted naphthyl) aminocarbonyl, (aminocarbonyl (Cl- Cd) alkyl) aminocarbonyl, (amino (Cl- Cd) alkyl) aminocarbonyl, hydroxyamidino, ureido, (halo (C1-C8) alkylcarbonyl) ureido, ureido (C1-C8) alkyl, glycinamide, mono (C1-C8) alkylglycinamide, aminocarbonylglycinamide, ((Cl-Cd) alkoxy (Cl-C8) alkylcarbonyl) glycinamide, (aminocarbonyl) ((Cl-Cd) alkyl) glycinamide, ((Cl-Cd) alkoxycarbonylamino (C1-C8) alkylcarbonyl) glycinamide, alaninamide, and (heterocyclyl of 3 to 15 members which consists of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (C1-C8) alkyl. 23. The compound of claim 22 wherein: R2 is 4- fluoro; R3 is phenyl substituted at the 4-position with chlorine and optionally substituted at the 2-position by aminocarbonyl, ureido, or glycinamide; and one R8 is hydrogen and the other R8 is selected from the group consisting of amino, (C1-C8) alkylcarbonylamino, (C3-C10) cycloalkylcarbonylamino, (C3-C10) cycloalkyl (Cl-Cd) alkylcarbonylamino, (C1-C8) alkoxycarbonylamino, (C 1 -C 8) alkylsulfonylamino, (optionally substituted phenyl or naphthyl) carbonylamino, (C 1 -C 8) lcoxycarbonyl (Cl-Cd) alkylcarbonylamino, (C 1 -C 8) alkylcarbonylamino (C 1 -C 8) alkyl, (C 3 -) C10) cycloalkylcarbonylamino (C1-C8) alkyl, (Cl-Cd) alkoxycarbonylamino (C1-C8) alkyl, (heterocyclyl of 3 to 15 members consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylamino (C1-C8) alkyl, (phenyl or optionally substituted naphthale) sulfonylamino, (Cl-Cd) alkylsulfonylamino (C1-C8) alkyl, ureido, mono (C1-C8) alkylureido, monohalo (Cl- Cd) alkylureide, ureido (Cl-Cd) alkyl, mono (Cl-Cd) alkylureido (C 1 -C 8) alkyl, monohalo (Cl-Cd) alkylureido (Cl-Cd) a alkyl, and amino (Cl-Cd) alkyl. 24. The compound of claim 23 selected from the group consisting of the following compounds: (trans) -1- (2- (4-chlorophenyl) -3- (methylsulfonylamino) propyl) carbonyl-2, 5-dimethyl-4 - (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -3- (acetylamino) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -2- (methylsulphonylamino) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; . (trans) -1- (2- (4-chlorophenyl) -2- (acetylamino) ethyl) carbonane-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -2- (amino) ethyl) carbonyl-2, 5-dirnethyl-4- (4-fluorobenzyl) piperazine; . (trans) -1- (2- (4-chloro-enyl) -2- (ureido) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -3- (ureido) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -3-amino) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -3- (t-butoxycarbonylamino) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -2- ((ethoxycarbonylmethylcarbonylamino) ethyl) carbonyl-2, 5-dimethyl-4- (4-fluo-robenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -2- (N'-iso-propyl-ureido) ethyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- ( 4-chlorophenyl) -2- (N r- (2-chloroethyl) ureido) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; - (trans) -1- (2- ( 4-chlorophenyl) -2- ((2-nitrophenyl) carbonylamino) ethyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -2 - ((4-methoxyphenylmethyl) carbonylamino) ethyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -2- ((2,4 - dinitrophenyl) sulfonylamino) ethyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -2- (cyclopropylcarbonylamino) ethyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -2- ((2-cyclopropylethyl) carbonamino) ethyl) ca rbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -3- ((2-methylpropyl) carbonylamino) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -3- (cyclopentylcarbonylamino) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -3- (Nf- (t-butyl) ureido) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -i- (2- (4-chlorophenyl) -3- (N '- (ethyl) ureido) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; -. (trans) -1- (2- (4-chlorophenyl) -3- (N '- (3-choropropyl) ureido) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; and (trans) -1- (2- (4-chlorophenyl) -3- ((morpholin-4-yl) carbonylamino) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine. 25. The compound of claim 1 wherein: RJ is a heterocyclic ring system substituted by one or more substituents selected from the group consisting of hydrogen, hydroxy, halo, (C1-C8) alkyl, (Cl-Cd) alkylsulfonyl , (phenyl or optionally substituted naphthyl) sulfonyl, (Cl-Cd) alkoxy, hydroxy (C1-C8) alkoxy, halo (Cl-Cd) alkyl, formyl, nitro, cyano, halo (Cl-Cd) alkoxy, (C2-) C8) alkenyl, (C2-C8) alkynyl, optionally substituted phenyl or naphthyl, (optionally substituted phenyl or naphthyl) (Cl-Cd) alkyl, amino, mono (Cl-Cd) alkylamino, di (C1-C8) alkylamino , mono (optionally substituted phenyl or naphthyl) amino, mono (optionally substituted phenyl or naphthyl) (Cl-Cd) alkylamino, (Cl-Cd) alkylcarbonylamino, (Cl-Cd) alkoxycarbonylamino, (C2-Cd) alkenylcarbonylamino, (C3-) C10) cycloalkylcarboniland.no, (optionally substituted phenyl or naphthyl) carbonylamino, halo (Cl-Cd) alkylcarbonylamino, (Cl-Cd) alkoxy (Cl-Cd) alkylcarbonylamino, (Cl-Cd) alkoxycarbonyl (Cl-Cd) alkylcarbonylamino, ((C 1 -C 8) alkylcarbonyl) ((C 1 -C 8) alkyl) amino, ((C 1 -C 8) alkoxycarbonyl) ((Cl-Cd) alkyl) amino, ( C1-C8) alkylsulfonylamino, amino (Cl-Cd) alkyl, mono (Cl-Cd) alkylamino (Cl- -Cd) alkyl, di (Cl-Cd) alkylamino (Cl-Cd) alkyl, (Cl-Cd) alkylcarbonylamino (C1-C8) alkyl, (optionally substituted phenyl or naphthyl) carbonylamino (Cl-Cd) alkyl, ((C1-C8) alkylcarbonyl) ((Cl-Cd) alkyl) amino (Cl-Cd) alkyl, (C1-C8) ) alkoxycarbonylamino (C1-C8) -alkyl, carboxy, (Cl-Cd) alkoxycarbonyl, (optionally substituted phenyl or naphthyl) (Cl-Cd) alkoxycarbonyl, (Cl-Cd) alkylcarbonyl, (optionally substituted phenyl or naphthyl) carbonyl, (optionally substituted phenyl or naphthyl) (Cl-Cd) alkylcarbonyl, aminocarbonyl, mono (Cl-Cd) alkylaminocarbonyl, di (Cl- Cd) alkylaminocarbonyl , mono (optionally substituted phenyl or naphthyl) aminocarbonyl, amino (C 1 -C 8) alkylcarbonyl, mono (C 1 -C 8) alkylaminocarbonyl (C 1 -C 8) alkyl, di (C 1 -C 8) alkylaminocarbonyl (C 1 -C 8) alkyl, mono (phenyl or optionally substituted naphthyl) aminocarbonyl (Cl-Cd) alkyl, guanidino, ureido, mono (Cl-Cd) alkylureido, ureido (Cl-Cd) alkyl, mono (Cl-Cd) alkylureido (Cl-C8) alkyl, and glycinamide. 26. The compound of claim 25 wherein: R4 is -O-, - N (R7) - or -C (R8) -; - R5 is a (C1-C8) alkylene chain; R7 is selected from the group consisting of hydrogen, (Cl-Cd) alkyl, phenyl or optionally substituted naphthyl, (optionally substituted phenyl or naphthyl) (C1-C8) alkyl, (C1-C8) alkylcarbonyl, (Cl- Cd) alkylcarbonyl ( Cl-Cd) alkyl, (optionally substituted phenyl or naphthyl) (Cl-Cd) alkylcarbonyl, (optionally substituted phenyl or naphthyl) (Cl- Cd) alkylcarbonyl (Cl-Cd) alkyl, aminocarbonyl, mono (Cl-Cd) alkylaminocarbonyl, di (Cl-Cd) alkylaminocarbonyl, and (Cl-Cd) alkoxycarbonyl; and each R8 is selected from the group consisting of hydrogen, (Cl-Cd) alkyl, phenyl or optionally substituted naphthyl, (optionally substituted phenyl or naphthyl) (C1-C8) alkyl, hydroxy, (Cl-Cd) alkoxy, hydroxy ( C1-C8) alkyl, (C1-C8) alkoxy (Cl-Cd) alkyl, amino, mono (C1-C8) alkylamino, di (. C1-Cd) alkylamino ,. (Cl-Cd) alkylcarbonylamino, (C3-C10) cycloalkylcarboniland.no, (C3-C10) cycloalkyl (Cl-Cd) alkylcarbonylamino, - (C1-C8) alkoxycarboniland.no, (C1-C8) alkylsulfonylamino, (phenyl) or optionally substituted naphthyl) carbonylamino, (Cl-Cd) alkoxycarbonyl (Cl-Cd) alkylcarbonylamino, ((Cl-Cd) alkylcarbonyl) ((Cl-Cd) alkyl) amino, (optionally substituted phenyl or naphthyl) (C 1 -C 8) alkylcarbonylamino, ((phenyl or optionally substituted naphthyl) (Cl-Cd) alkylcarbonyl) ((Cl-Cd) alkyl) amino, (Cl-Cd) alkylcarbonylamino (Cl-Cd) alkyl, (C3-C10) cycloalkylcarboniland.no (Cl -Cd) alkyl, (Cl-Cd) alkoxycarbonylamino (C1-C8) alkyl, ((Cl-Cd) alkylcarbonyl) ((Cl-Cd) alkyl) amino (Cl-Cd) alkyl, (optionally substituted phenyl or naphthyl) ( Cl-Cd) alkylcarbonylamino (Cl-Cd) alkyl, (heterocyclyl of 3 to 15 members consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylamino ( Cl-Cd) alkyl, ((optionally substituted phenyl or naphthyl) (Cl-Cd) alkylcarbonyl) ((Cl-Cd) alkyl) amino (Cl-Cd) alkyl, (optionally substituted phenyl or naphthyl) sulfonylamino, ( C1-C8) alkylsulfonylamino (Cl-Cd) alkyl, ureido, mono (Cl-Cd) alkylureido, monohalo (Cl- Cd) alkylureido, di (C1-C8) alkylureido, ureido (Cl- Cd) alkyl, mono (Cl-) Cd) alkylureido (Cl-Cd) alkyl, di (C 1 -C 8) alkylureido (C 1 -C 8) alkyl, monohalo (Cl-Cd) alkylureido (Cl-Cd) alkyl, amino (Cl-Cd) alkyl, mono (Cl-) Cd) alkylamino (Cl-Cd) alkyl, di (Cl-Cd) alkylamino (Cl-Cd) alkyl, carboxy (C 1 -C 8) alkyl, (C 1 -C 8) alkoxycarbonyl (Cl-Cd) alkyl, aminocarbonyl (Cl-Cd) alkyl, mono (Cl-Cd) alkylaminocarbonyl (C1-C8) alkyl, and di (Cl-Cd) alkylaminocarbonyl (Cl-Cd) alkyl. 27. The compound of claim 26 wherein: R4 is -0-; R5 is methylene; and R 6 is -C (0) -. 28. The compound of claim 26 wherein: R1 is one or more substituents selected from the group consisting of halo, (C1-C8) alkyl, (C3-C10) cycloalkyl, (C3-C10) cycloalkylamino (C1- C8) alkyl, halo (C1-C8) alkyl, hydroxy (Cl-Cd) alkyl, hydroxy (C2-C8) alkenyl, hydroxy (C2-C8) alkynyl,

(hydroxy) (optionally substituted phenyl or naphthyl) (Cl-Cd) alkyl, cyano (Cl-Cd) alkyl, halo (Cl- Cd) alkylcarbonylamino (Cl-C) alkyl, (Cl-Cd) alkoxy (Cl-Cd) alkyl, (optionally substituted phenyl or naphthyl) (Cl-Cd) alkoxy (Cl-Cd) alkyl, (Cl-Cd) alkylthio (Cl-Cd) alkyl, hydroxy (C 1 -C 8) alkylthio (Cl-Cd) alkyl, amino (Cl-Cd) alkyl, mono (Cl-C8) alkylamino (Cl-Cd) alkyl, di (C1-C8) alkylamino (Cl-Cd) alkyl, mono (phenyl or optionally substituted naphthyl) amino (Cl-) Cd) alkyl, mono-phenyl or optionally substituted naphthyl) (Cl-Cd) alkylamino (C 1 -C 8). alkyl, azido (Cl-Cd) alkyl, • mono (Cl-Cd) alkylureido (Cl-Cd) alkyl, ((Cl-Cd) alkoxycarbonyl (Cl-Cd) alkyl) ureido (Cl-Cd) alkyl, hydroxy (Cl-Cd) alkylamino (Cl-Cd) alkyl, (optionally substituted phenyl or naphthyl) oxy (Cl-Cd) alkylcarbonyloxy (Cl-Cd) alkyl, (phenyl or optionally substituted phenyl) (C1-C8) alkoxy (Cl- Cd) alkylcarbonyloxy (C 1 -C 8) alkyl, (C 1 -C 8) alkylcarbonyl (C 1 -C 8) alkyl, (C 1 -C 8) alkoxycarbonyl, (C 1 -C 8) alkoxycarbonyl (C 1 -C 8) alkyl, and (heterocyclyl from 3 to 15 members consisting of carbon atoms and between one and five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (Cl-Cd) alkyl; and R2 is one or more substituents selected from the group consisting of hydrogen and halo. 29. The compound of claim 2d R3 selected from the group consisting of azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl, carbazolyl, cinnolinyl, decahydroisoquinolyl, dioxolanyl, furyl, isothiazolyl, quinuclidinyl, imidazolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, indole, isoindolyl, indolinyl, isoindolinyl, indanyl, indolizinyl, isoxazolyl, isoxazolidinyl-, morpholinyl, naphthyridinyl, oxadiazolyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl , 2 ~ oxoazepinyl, oxazolyl, oxazolidinyl, piperazinyl, 4- piperidonyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyrazolidinyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl thiazolyl, thiazolidinyl, thiadiazolyl, triazolyl, tetrazolyl, tetrahydrofuryl, tetrahydropyranyl, thienyl, thiamorpholinyl, thiamorpholinyl sulfoxide, and thiamorpholinyl sulfone. 30. The compound of claim 29 wherein R3 is benzopyranyl, benzopyranonyl, benzfuranyl, benzofuranonyl-, quinolinyl, indolyl, indolinyl, oxazolyl, imidazolyl, or benzothienyl. 31. The compound of claim 30, namely: (trans) -1- (- (benzo [b] pyran-2-on-7-yloxy) methyl) carbonyl-2, 5-dimethyl-4- ( 4-fluorobenzyl) piperazine. 32. The compounds (5-Chloro-2- [- (E) -3- [(R) -4- (4-fluorobenzyl) -2-methylpi- perazin-1-yl] -3-oX-propenyl] -phenyl) -urea, N- (5-Chloro-2- [(E) -3- [(R) -4- (4-fluorobenzyl) -2-methylpiperazin-1-yl] -3-oxo-propenyl] -phenyl) - methanesulfonamide, (5-Chloro-2- [(E) -3- [(2R, 5S) -4- (4-fluorobenzyl) -2,5-di-methyl-piperazin-1-yl] -3-oxo-propenyl] -phenyl ) -urea, N- (5-Chloro-2- [(E) -3- [(2R, 5S) -4- (4-fluorobenzyl) -2,5-dimethylpiperazin-1-yl] -3-sxopropenyl] phenyl) - methanesulfonamide, (5-Chloro-2. {(E) -3- [4- (4-fluoro-benzyl) -2-methyl-piperazin-1-yl] -3-oxo-methyl ester -propenyl.}. - phenyl) -acetic, • 5-chloro-2- acid. { (E) -3- [(R) -4- (4-Fluoro-benzyl) -2-methyl-piperazin-1-yl] -3-oxo-propenyl} - benzoic, (5-chloro-2- {. (E) -3- [(R) -4- (4-fluoro-benzyl) -2-methyl-pi- perazin-1-yl] -3-oxo -propenyl.} -4-methoxy-phenyl) -urea, (5-Chloro-2- { (E) -3- [(R) -4- (4-fluoro-benzyl) -2-methyl- piperazin-1-yl] -3-oxo-propenyl} -4-trifluoromethoxy-phenyl) -urea, 5-chloro-2-methyl methylester. { (E) -3- [(R) -4- (4-Fluorobenzyl) -2-methyl-piperazin-1-yl] -3-oX-propenyl} -4- methoxy-benzoic acid (5-Chloro-2- { 2- [4- (4-fluoro-benzyl) - (2R) -2-methyl-piperazin-1-yl] -2-oxo-ethoxy .}.-phenyl) - acetic, (5-Bromo-2- { 2- [4- (4-fluoro-benzyl) - (2R, 5S) -2,5-dimethyl-piperazin-1-yl] -2-oxo-ethoxy}-phenyl) -acetic acid. (5-Bromo-2- { 2- [4- (4-fluoro-benzyl) .- (2R) -2-methyl-piperazin-1-yl] -2-oxo-ethoxy.} - phenyl) - acetic, - 3- (5-Chloro-2 ~ {2 - '[4- (4-fluoro-benzyl) - (2R) -2-methyl-piperazin-1-yl] -2- oxo-ethoxy.]. phenyl) -propionic acid (5-Chloro-2 ~ { 2- [4- (3,4-difluoro-benzyl) - (2R, 5S) -2,5-dimethyl- piperazin-1-yl] -2-oxo-ethoxy.] - phenyl) -acetic acid (5-Chloro-2- { 2- [4- (4-chloro-benzyl) - (2R, 5S) -2,5-di-methyl-piperazin-1-yl] -2-oxo-ethoxy.} - phenyl) -acetic acid (5-Chloro-2- { 2- [(2R) -2- ethyl-4- (4-fluoro-benzyl) -piperazin-1-yl] -2-oxo-ethoxy.} - phenyl) -acetic acid (5-Bromo-2-. {2- [(2R)] -2-ethyl-4- (4-fluoro-benzyl) -. Piperazin-1-yl] -2-oxo-ethoxy.} - phenyl) -acetic acid (5-Chloro-2-. {2- [4- (4-chloro-benzyl) - (2R) -2-methyl-piperazin-1-yl] -2-oxo-ethoxy.] -phenyl) -acetic acid (5-Chloro-2-. { 2- [4- (3, '4-difluoro-benzyl) - (2R) -2-methyl-piperazin-1-yl] -2-oxo-ethoxy.] -phenyl) -acetic acid - (5-Chloro-2- { 2- [4- (4-fluoro-be ncil) - (2R, 5S) -2,5-dimethyl-piperazin-1-yl] -2-oxo-ethoxy} phenyl) - acrylic, N - [(5-Chloro-2- { 2- [4- (4-fluoro-benzyl) - (2R, 5S) -2,5-diraethyl-piperazin-1-yl] -2-oxo-ethoxy.}.-Phenyl) -acetyl] -methanesulfonamide, N- (5-Chloro-2- { 2- [4- (4-fioro-benzyl) - (2R, 5S) -2 , 5- dimethyl-piperazin-1-yl] -2-oxo-ethoxy.}. -benzoyl) -methanesulfonamide, N - [(5-Chloro-2- { 2- [4- (4-fluoro-benzyl ) - (2R, 5S) -2,5-di-methyl-piperazin-1-yl] -2-oxo-ethoxy.} - phenyl) -acetyl] - C, C, C-trifluoromethanesulfonamide, acid ( 5-Chloro-2- {2 ~ [4- (4-fluoro-benzyl) - (2R, 5S) -2,5- dimethyl-piperazin-1-yl] -2-o'xo-ethoxy. .-phenyl) -oxo-acetic acid (5-Chloro-2- { 2- [4- (4-fluoro-benzyl) - (2R, 5S) -2,5- dimethyl-piperazin-1-yl) ] -2-oxo-ethoxy.}. -phenoxy) -acetic acid 2- (5-Chloro-2- { 2- [4- (4-fluoro-benzyl) - (2R, 5S) -2, 5- diraethyl-piperazin-1-yl-2-oxo-ethoxy.] -phenoxy) -2- ethyl-propionic acid (5-Chloro-2-. {2- [4- (4-fluoro-benzyl) ) - (2R, 5S) -2,5- dimethyl-piperazin-1-yl] -2-oxo-ethoxy.} - phenoxy) -difluoroacetic acid (5-chloro ~ 2- { 2- [4- (4-Fluoro-benzyl) - (2R) -2-methyl-piperazin-1-yl] -2-oxo-ethoxy} phenyl) -methanesulfonamide

5 N- [5-chloro-2- [2- [(2R, 5S) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] phenyltrifluoromethanesulfonamide, 5-chloro-2- [2- [(2R, 5S) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] -benzenesulfonamide. 10 (5-Chloro-2- { 2- [4- (4-fluoro-benzyl) - (2R, 5S) -2,5-dimethyl-piperazin-1-yl] -2-oxo-ethoxy}-phenyl) -methanesulfonic acid (5-Chloro-2- { 2- [4- (4-fluoro-benzyl) - (2R) -2-methyl-piperazin-1-yl] -2-oxo -ethoxy.}. -phenyl) -methanesulfonyl-5-co, (5-Brpmo-2- { 2- [4- (4-fluoro-benzyl) - (2R, 5S) -2,5- • ' dimethyl-? iperazin-1-yl] -2-oxo-ethoxy.} - phenyl) -methanesulfonic acid (5- Bromo -2- { 2- [4- (4-fluoro-benzyl) - (2R ) -2-0 methyl-piperazin-1-yl] -2-oxo-ethoxy.} - phenyl) -methanesulfonic acid (5-Chloro-2- { 2- [4- (4-fluoro-benzyl) ) - (2R, 5S) -2,5-Dimethyl-piperazin-1-yl] -2-oxo-ethoxy.} - phenyl) -ethanesulfonic acid (5-Chloro-2- { 2 ~ [4 - (4-fluoro-benzyl) - (2R, 5S) -2,5-dimethyl-pipera? In-1-yl] -2-oxo-ethoxy}. -benzyl) -phosphonic acid monoethyl ester (5- Chloro-2- {2- [4- (4-fluorobenzyl) - (2R, 5S) -2,5-dimethyl-piperazin-1-yl] -2-oxo-ethoxy} -benzyl) phosphonic acid, 5-Chloro-2- acid. { 2- [4- (4-Fluoro-benzyl) - (2R5S) -2,5-dimethyl-piperazin-1-yl] -2-oxo-ethoxy} -benzyl) - phosphonamide 5-chloro-2- [2- [(2R, 5S) -4 - [(4-fluorophenyl) methyl] -2,5-diraethylpiperazinyl] -2-oxoethoxy] benzoic acid methyl ester 5-bromo-2- [2- [(21? 55) -4- [(4-fluoro-phenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzeneacetic; 5-bromo-2- [2- [(21?) -4- [(4-fluorophenyl) methyl] -2-methylpiperazinyl] -2-oxoethoxy] benzeneacetic acid methyl ester 5-bromo-2- [2-methyl] acid ester - ['(21? 55) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzoic acid methyl ester 5-bromo-2- [2- [(21? 5S) -4- [(4-fluoro-phenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] -4-methoxybenzoic acid methyl ester 5-chloro-2- [2- [(21? 55) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] -4-methoxybenzoic acid methyl ester 5-chloro-2- [2- [(21? 5S) -4- [ (4-fluoro-phenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] -4-methylbenzoic acid; 4,5-dichloro-2- [2- [(21?, 55) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzoic acid methyl ester; 5-chloro-2- [2- [(21?, 55) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2- oxoethoxy] -4- (trifluoromethyl) benzoic acid methyl ester; 5-chloro-2- [2- [(2 £, 5S) -2,5-diethyl-4- [(4-fluorophenyl) methyl] piperazinyl] -2-oxoethoxy] enzoic acid methyl ester; 5-bromo-2- [2- [(21? 55) -2,5-diethyl-4- [(4-fluorophenyl) methyl] piperazinyl] -2-oxoethoxy] -4-methoxybenzoic acid methyl ester of 5-bromo-2- [2- [(21?) -4- [(5-chloro-2-thienyl) methyl] -2-methylpiperazinyl] -2-oxo-ethoxy] benzeneacetic acid 5-chloro-2 acid - [2- [(2l?, 5S) -4- [(4-fluorophenyl) methyl '] -2-, 5-dimethylpiperazinyl] -2-oxoethoxy] benzenesulfonic acid; 5-chloro-2- [2- [(21?) -4- [(4-fluorophenyl) methyl] -2-methylpiperazinyl] -2-oxoethoxy] benzenesulfonic acid; 5-chloro-4- (dimethylamino) -2- [2- [(2R, 5S) -4- [(4-fluorophenyl) butyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzoic acid 5-chloro -2- [2- [(21? 55) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzoic acid; 5-bromo-2- [2- [(21? 55) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzeneacetic acid 5-bromo-2- [2 -p'21?) - 4- [(4-fluorophenyl) methyl] -2-butylpiperazinyl] -2-oxoethoxy] benzene acetic acid; 5-bromo-2- [2- [(21? 55) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzoic acid; acid-5-bromo-2- [2- [(2R, 55) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] -4-methoxybenzoic acid 5-chloro-2 - [2- [(21? 5S) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] -4-methoxy benzoic; 5-Chloro-2- [2- [(2l?, 5S) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] -4-methyl-benzoic acid 4, 5 -dichloro-2- [2- [(21? 55) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzoic acid, 5-chloro-2- [ 2- [(21? 5S) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] -A- (trifluoromethyl) benzoic; 5-chloro-2- [2 - [(2 £, 5S) -2,5-diethyl-4 - [(4-fluorophenyl) methyl] piperazinyl] -2-oxoethoxy] benzoic acid; 5-bromo-2- [2- [(21? 55) -2,5-diethyl-4- [(4-fluorophenyl) methyl] piperazinyl] -2-oxoethoxy] -4-methoxy-benzoic acid; 5-chloro-4-ethoxy-2- [2- [(21? 55) -4- [(4-fluoro-phenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzoic acid; 4-amino-5-chloro-2- [2- [(21? 55) -4- [(4-fluorophenyl) methyl] -2,5-dimethyl-iperazinyl] -2-oxoethoxy] benzoic acid; 5-chloro-2- [2- [(21? 5S) -5-ethyl-4- [(4-fluorophenyl) methyl] -2-methylpiperazinyl] -2-oxoethoxy] benzoic acid; 5-chloro-2- [2- [(21? 5S) -5-ethyl-4- [(4-fluorophenyl) methyl] -2-methylpiperazinyl] -2-oxoethoxy] -4-methoxy benzoic acid; 5-chloro-2- [2- [(21? 5S) -2,5-diethyl-4- [(4-fluorophenyl) methyl] piperazinyl] -2-oxoethoxy] -4-methoxy benzoic acid; 4-chloro-2- [2- [(21?, 55) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzoic acid;

2- [2- [(2R, 5S) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] -5-methyl benzoic acid in the production of a medicament for treatment and prevention of endometrosis in humans 33. A pharmaceutical composition useful for the treatment of endometrosis in a female human needing such treatment, comprising a therapeutic effective amount of a compound according to claim 1 34. Compounds that respond to the formulas: 5-bromo-2- [2- [(2R, 5S) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] methyl ester] -2- oxoethoxy] benzenacetic acid - 5-bromo-2- [2- [(2R, 5S) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzeneacetic acid methyl ester 5-bromo -2- [2- [(2R) -4- [(4-fluorophenyl) methyl] -2-methylpiperazinyl] -2-oxoethoxy] benzeneacetic acid 5-bromo-2- [2- [(2R) -4- [ (.4-fluorophenyl) methyl] -2- methylpiperazinyl] -2-oxoethoxy] bencenacé methyl '5-bromo-2- [2- [(2R, 5S) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzoic acid methyl ester 5-bromo acid -2- [2- [(2R, 5S) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] -4-methoxybenzoic acid 5-bromo-2- [2- [ (2R, 5S) -4- [(4-fluorophenyl) methyl] -2,5-diraethylpiperazinyl] -2-oxoethoxy] -4-methoxybenzoic acid methyl ester 5-chloro-2- [2- [(2R, 5S)] -4- [(4- fluorophenyl) methyl] -2,5-dimethyl-iperazinyl] -2-oxoethoxy] -4-methoxybenzoic acid 5-chloro-2- [2- [(-2R, 5S) -4- [ (4-fluorophenyl) methyl] -. 2,5-dimethylpiperazinyl] -2-oxoethoxy] -4-methoxybe zoic acid 5-chloro-4-ethoxy-2- [2- [(2R, 5S) -4- [(4-fluorophenyl) methyl] -2, 5-dimethylpiperazinyl] -2-oxoethoxy] benzoic acid 4-amino-5-chloro-2- [2- [(2R, 5S) -4- [(4-fluoro-phenyl) methyl] -2,5-dimethylpiperazinyl] -2- oxoethoxy] benzoic acid 5-chloro-4- (dimethylamino) -2- [2- [(2R, 5S) -4- [(4-fluorophenyl), methyl] -2,5-dimethylpiperazinyl] -2- oxoethoxy] benzoic acid methyl ester 5-chloro-2- [2- [(2R, 5S) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] -4-methylbenzoic acid '5-chloro-2- [2- [(2R, 5S) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] -4-methylbenzoic acid methyl ester, 5-dichloro -2- [2- [(2R, 5S) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzoic acid 4,5-dichloro-2- [2- [( 2R, 5S) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoetbxy] benzoic acid-5-chloro-2- [2- [(2R, 5S) -4- [(4- fluorophenyl) methyl] -2, 5-dimethylpiperazinyl] -2-oxoethoxy] -4- (tri'fluoromethyl) benzoic acid 5-chloro-2- [2- [(2R, 5S) -4- [(4-fluorophenyl) methyl] -2, 5- dimethylpiperazinyl] -2-oxoethoxy] -4- (trifluoromethyl) benzoic acid 5-chloro-2- [2- [(2R, 5S) -5-ethyl-4- [(4-fluoro-phenyl) methyl] -2- methylpiperazinyl] -2-oxoethoxy] benzoic acid 5-chloro-2- [2- [(2R, 5S) -5-ethyl-4- [(4-fluoro-phenyl) methyl] -2-methylpiperazinyl] -2-oxoethoxy ] -4- methoxybenzoic acid methyl ester 5-chloro-2- [2- [(2R, 5S) -2,5-diethyl-4- [(4-fluorophenyl) methyl] piperazinyl] -2-oxoethoxy] benzoic acid -chloro-2- [2- [(2R, 5S) -2,5-diethyl-4- [(4-fluorophenyl) methyl] piperazinyl] -2-oxoethoxy] benzoic acid methyl ester 5-bromo-2- [2 - [(2R, 5S) -2,5-diethyl-4- [(4-fluorophenyl) methyl] piperazinyl] -2-oxoethoxy] -4-methoxybenzoic acid 5-bromo-2- [2- [(2R, 5S -2, 5-diethyl-4- [(4-fluorophenyl) methyl] piperazinyl] -2-oxoethoxy] -4-methoxybenzoic acid 5-chloro-2- [2- [(2R, 5S) -2, 5- diethyl-4- [(4-fluorophenyl) methyl] piper azinyl] -2-oxoethoxy] -4-methoxybenzoic acid 5-chloro-2- [2- [(2R, 5S) -4- [(4-fluorophenyl) methyl] -2,5-dimethylpiperazinyl] -2-oxoethoxy] benzenesulfonic acid 5-chloro-2- [2- [(2R) -4- [(4-fluorophenyl) methyl] -2-methylpiperazinyl] -2-oxoethoxy] benzenesulfonic acid