MXPA99011506A

MXPA99011506A - Piperazine derivatives and their use as anti-inflammatory agents

Info

Publication number: MXPA99011506A
Application number: MXPA/A/1999/011506A
Authority: MX
Inventors: G Bauman John; O Buckman Brad; F Ghannam Ameen; E Hesselgesser Joseph; Horuk Richard; Islam Imadul; Liang Meina; B May Karen; D Monahan Sean
Original assignee: Bayer Schering Pharma Aktiengesellschaft
Priority date: 1997-06-12
Filing date: 1999-12-10
Publication date: 2000-09-04

Abstract

This invention is directed to acyl piperazine derivatives which are useful as anti-inflammatory agents. This invention is also directed to pharmaceutical compositions containing the compounds of the invention, and methods of using the compounds to treat inflammatory disorders in humans.

Description

ES $ DERIVATIVES OF PIPERAZINE AND Sü USE AS ANTI-INFLAMMATORY AGENTS FIELD OF THE INVENTION The present invention is directed to piperazine derivatives and their pharmaceutically acceptable salts, which inhibit the activity of chemokines, MlP-la and RANTES, so they are useful as anti-inflammatory agents. It also relates to pharmaceutical compositions containing the pharmaceutically acceptable derivatives or salts, and methods of their use.

BACKGROUND OF THE INVENTION An important component of the inflammatory process involves the migration and activation of selected populations of leukocytes from the circulation and their accumulation in the affected tissue. Although the idea of leukocyte trafficking is not new, it has enjoyed a revival recently after the discovery and characterization of the selectin and integrin families of adhesion molecules and a large family of selective cytokine-like kytokines known as chemokines. The chemokine receptors are expressed in leukocytes and process signals after chemokine binding, so that such signals eventually transduce into migration or activation of the leukocytes towards the source of the chemokines. Therefore, by regulating the migration and activation of leukocytes from peripheral blood to extravascular sites in organs, skin, joints or connective tissue, chemokines play a critical role in maintaining host defense as well as in the development of the immune response. Originally, the family of chemokine molecules was divided into two groups: the subfamily "C-X-C" and the subfamily "C-'C". The characteristic feature of both subfamilies is the presence of four cysteine residues in highly conserved positions in the molecules. In the "C-C" chemokine subfamily, the first two residues are adjacent to one another, while in the "C-X-C" subfamily, the cysteine residues are separated by a single amino acid residue. A recent description of a chemokine "-C-". it seems to represent a new family of chemokines where the chemokine "-C" lacks two of the four cysteine residues present in the subfamily "C-C" or in the subfamily "C-X-C". A member of the "CC" subfamily of chemokine is the macrophage-inflammatory protein ("MlP-la)." It is expressed by cells such as macrophages, T and B lymphocytes, neutrophils and fibroblasts.A recent study (see Karpus, WJ et al., J. Immunol. (1995), Vol. 155, pp. 5003-5010) provides strong validation of the in vivo concept for a role of MlP-la in a model of experimental autoimmune encephalomyelitis (EAE) in multiple sclerosis, multiple sclerosis is an autoimmune disease mediated by T and B lymphocytes as well as by macrophages, resulting in extensive inflammation and demyelination of white matter in the central nervous system. antibodies to MlP-la prevent the development of both the initial and reminder disease and at the same time prevent the infiltration of mononuclear cells into the central nervous system. with the antibodies is also able to decrease the severity of the clinical disease in process. These results lead researchers to conclude that MlP-la plays an important role in the etiology of multiple sclerosis. In addition, another study (see Godis a, R. et al., J. Neuroi munology (1995), Vol. 58, p. 167-176) demonstrates an up-regulation of mRNA for many guimiocins, including MlP-la in the lesions and in the spinal cord of SJL mice (a strain of mice susceptible to Th._ diseases such as EAE) during the course of acute EAE. RANTES is another member of the chemokine subfamily C-C (the name RANTES is an acronym derived from some of the original observed and predicted characteristics of a protein and its gene: Regulated before activation of normal T cells supposedly secreted). A wide variety of tissues have been found that express RANTES in a similar pattern to MlP-la. There is strong evidence linking RANTES to the rejection of organ transplants, particularly of the kidney. The infiltration of mononuclear cells into the interstitium of transplanted organs organ transplants is the hallmark of acute cellular rejection. This cellular infiltrate consists mainly of T cells, macrophages and eosinophils. In a study of RANTES expression during acute renal allograft rejection, it has been found that the expression of RANTES mRNA in infiltrating mononuclear cells and in renal tubular epithelial cells and RANTES itself is found to be bound to the endothelial surface by the microvasculature with the rejection graft (see Pattison, J. et al., Lanc (1994), Vol. 343, pp. 209-1 and Wiedermann, CJ et al., Curr. Biol. (1993), Vol. 3, p. 735-739). There is also evidence from numerous studies involving the abnormal production of RANTES in the progression of rheumatoid arthritis (see Rathanaswami, P. et al., J. Biol. Chem (1993), Vol. 268, pp. 5834-5839 and Sno den. , N. et al., Lancet (1994), Vol. 343, pp. 547-548). Rheumatoid arthritis is a chronic inflammatory disease characterized in part by a memory T lymphocyte and infiltration of monocytes, which are considered to be mediated by chemotactic factors released by inflamed tissues. In addition, there is strong evidence from other studies involving RANTES in the pathophysiology of rheumatoid arthritis (see Barnes, DA et al., J. Clin. Invest. (1998, in press) and Plaster-Zyberk, CA et al., Immunol Lett. (1997), Vol 57, pp. 117-120). For example, in a model of adjuvant-induced arthritis (AIA) in rats, antibodies to RANTES greatly reduce the development of the disease in rats, induced by AIA. These studies and others provide strong evidence that MlP-la concentrations are increased in multiple sclerosis EAE models and that RANTES levels are increased in rheumatoid arthritis and in kidney transplant rejection (see, for example, Glabinski, AR et al., Am, J. Pathol. (1997), Vol. 150, pp. 617-630, Glabisnki, AR et al., Methods Enzymol. (1997), Vol. 288, 182-190; and Miyagishi, RS et al., J. Neuroimmunol. (1997), Vol. 77. pp. 17-26). Furthermore, as described above, these chemokines are chemoattractants for T cells and monocytes which are the main cell types that are involved in the pathophysiology of these diseases. Therefore, any molecule that inhibits the activity of any of these chemokines may be beneficial in treating these diseases and therefore may be useful as an anti-inflammatory agent.

RELATED DESCRIPTIONS Piperazine derivatives of the type similar to the compounds of the invention are known in the literature and are useful for various pharmaceutical indications, particularly as cardiotonic, neurotrophic or anti-inflammatory agents. For example, published European patent application 0 702 010 (Adir) discloses certain piperazine derivatives which are useful as central nervous system depressants in the treatment of Alzheimer's disease and other diseases of immunological origin, such as arthritis and intestinal peristalsis. Published European Patent Application 0 655 442 (Fujisawa) discloses similar piperazine derivatives as tachykinin antagonists useful in the treatment of inflammatory diseases such as rheumatoid arthritis and in osteoarthritis. A published Czech patent application, 260089 and a related article, Valenta, V. et al., Collection Czechoslovak Chem. Commun. (1987), Vol. 52, pp. 3013-3023, describe piperazine derivatives as potential neurotrophic and cardiovascular agents. The published European patent application 0 252 422 (Mitsubishi) and the published German patent application number 3614363 (Hoechst) describe piperazine derivatives useful as cardiotonic agents. The published European patent application 0 190 685 (G.D. Searle) describes piperazine derivatives which block the 5-lipoxygenase pathway of the arachidonic acid cascade, so they are useful in the treatment of allergic reactions and hypersensitivity and inflammation. The published patent application PCT 096/34864 (Schering Plow) describes piperazine derivatives useful as neurokinin antagonists.

All references mentioned above are incorporated herein by reference. None of the above references describe the piperazine derivatives described herein or their usefulness in the treatment of inflammatory disorders in humans by inhibiting the activity of chemokines, MlP-la and RANTES.

BRIEF DESCRIPTION OF THE INVENTION This invention is directed to compounds or their pharmaceutically acceptable salts which inhibit the activity of chemokines, MlP-la and RANTES and are therefore useful as pharmacological agents for the treatment of inflammatory disorders in humans. Accordingly, in one aspect, this invention provides compounds of the following formula (la): (the) wherein: Rla is one or 'more substituents independently selected 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, haloalkylcarbonyl-aminoalkyl, (alkoxy) aralkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthioalkyl, alkylsulphonylalkyl, alkyl su fonyl alkyl , hydroxyalkylthioalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, monoalkylaminoalkyl, monoaralkylaminoalkyl, alkylcarbonylaminoalkyl, (alkylcarbonyl) - (alkyl) aminoalkyl, azidoalkyl, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, (alkoxycarbonylalkyl) ureidoalkyl, alkoxycarbonylaminoalkyl, hydroxyalkylamino alkylaminoalkyl, ariloxialquilcarboniloxialquilo, alkylcarbonyloxyalkyl alkoxy-, aralcoxialquilcarboniloxi- alkyl, alkylcarbonyl, alkylcarbonylalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, aralkylcarbonyl, aminocarbonyl, aminocarbonyl monoalkyl, dialkylaminocarbonyl, monoaryl-aminocarbonyl, monoaralquilaminocarbonilo, carboxy-alkyl, alkoxycarbonylalkyl, aralkoxycarbonyl-alkyl, aminocarbonyl, monoalkylaminocarbonyl-alkyl, dialkylaminocarbonylalkyl, monoarylaminocarbonylalkyl, monoaralkylaminocarbonylalkyl, arylsulfonyl, heterocyclyl and heterocyclylalkyl, plus substituents 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, (hydr oxy) cycloalkylalkyl, cicloalquiloamino, c i cloalquil aminoalkyl, (cycloalkylalkyl) amino, (cycloalkylalkyl) -aminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy) aralkyl, thioalkyl hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (Alkoxy) aralkyl, aryloxyalkyl, aralkoxyalkyl, amino, monoalkylamino, dialkylamino, monoarylamino, monoaralquilamino, aminoalkyl, monoalkylamino-alkyl, dialkylaminoalkyl, alkyl hidroxialquiloamino-, monoarilaminoalquilo, monoaralquilamino- alkyl, alkylcarbonylamino, (alkylcarbonyl) - (alkyl) amino, carbonylaminoalkyl , (Alquilocarbonil) (alkyl) aminoalkyl, alkoxy- carbonylamino, (alkoxycarbonyl) (alkyl) mino, alkoxycarbonylaminoalkyl, (alkoxycarbonyl) - (alkyl) aminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, alkylcarbonyl - alkyl, arylcarbonyl, arylcarbonylalkyl, aralkylcarbonyl , aralkyl carbonylalkyl, carboxyalkyl, alkoxycarbonylalkyl, aral coxycarbonyl to chyle, coxy alkylcarbonyloxyalkyl, aminocarbonyl, monoalkylaminocarbonyl, di-alkylaminocarbonyl, monoarylaminocarbonyl, monoaralkylaminocarbonyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoalkylaminocarbonylalkyl, monoaralkylaminocarbonylalkyl , amidino, guanidino. ureido, monoalquilureido, dialkylureido, u r e i do 1 qu i 1 or Monoa 1 qu i 1 u r e i do 1 qu i 1 or dialk yl our e idoalquil or I t Eroc i cl yl or and heterocyclylalkyl; R3 is a carboxylic ring system substituted by one or more substituents that are independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfyl, alkylsuf onyl, arylsuf onyl, alkyl thioalkyl , alkylsulphonylalkyl, alkylsulphonylalkyl, alkoxy, hydroxyalkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, aminoalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy) cycloalkylalkyl, cycloalkylamino, cycloalkylamino to chyle, Cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy) aralkyl, (monoalkylamino) aralkyl, (hydroxyalkyl) halkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy) aralkyl, aryloxyalkyl, aralkoxyalkyl, amino, monoalkylamino, dialkylamino, monoarylamino, monoaralkylamino, aminoalkylamino, heterocyclylamino, (cycloalkylalkyl) amino, alkylcarbonylamino, coxi lamino carboni, alkenyl lamino carboni, cycloalkylcarbonylamino, arilocarbonilamino, h e t e r o c i c l i l c a r b o n i l a m i n o, h to l or l q u i l c a r b o n i l a m i n or at carbonylamino coxialquil, the alquil¬ coxicarbonil alkylcarbonylamino, (alkylcarbonyl) amino (alkyl), (the coxicarbonil) (alkyl) amino, alquilsulf Onila ino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, hydroxyalkylaminoalkyl, monoarilaminoalquilo, monoaralquiloaminoalq Uilo, the qu Iloca rb or not l ami not to qu yl, arilcarbonilaminoalqu yl, (alkylcarbonyl) (alkyl) aminoalkyl, (cicloalquialquil) aminoalkyl, alkoxycarbonyl - 10 aminoalkyl, carbonylaminoalkyl alcoxicarbonilalquil-, (alkoxycarbonyl) - (alkyl) aminoalkyl, onilaminoalquilo alquilsulf, (alkylsulfonyl) (alkyl) aminoalkyl, arylsulfonyl - aminoalkyl, (arylsulf onyl) (alkyl) aminoalkyl, heterocyclylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, (hydroxyalkoxy) carbonyl, carboxyalkyl, to the coxycarbonyl alkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, dialkylaminocarbonyloxyalkyl, alkylcarbonyl-alkyl, aryl carbonyl alkyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, monoalkylaminocarbonyl, monoalkyl aralkyl aminocarbonyl (aminocarbonylalkyl) aminocarbonyl (monoalkylaminocarbonylalkyl) aminocarbonyl (carboxyalkyl) aminocarbonyl (alkoxycarbonylalkyl) -aminocarbonyl (aminoalkyl) ami no ca rb oni lo (hydroxyalkyl) aminocarbonyl aminocarbonylalkyl, monoalkyl a m i n o c a r b o n i l a l i l a l i i o di di ali l amino c arboni l al mono or alkylaminocarbonyl alkyl, monoaralkyl aminocarbonylalkyl, amidino, hydroxyamidino guanidino, ureido, monoalkylureido monoalkylureide, monoaralkylureide m or n or h a l a l i u u i e (monoalkyl) (monoaryl) ureido, dialkylureide diarylureido, (hal or alkylcarbonyl) ureido ureidoalkyl, monoalkylureidoalkyl dialquilureidoalquilo, monoariloureidoalquilo m or n or r to l q u i l u r e i d or l q u i l or monoha l or l qu i l u re i d or l qu i l or (haloalkyl) (alkyl) ureidoalkyl (alkoxycarbonylalkyl) ureidoalkyl, glycinamido manoalquilglicinamido I aminocarbonilglicinamido (alcoxialquilcarbonil) gl icinamido, (aminocarbonyl) (alkyl) glycinamido, (alcoxicarbonilalquilcarbonil) (alkyl) glycinamido, (alcoxicarbonilaminoalguilcarbonil) glycinamido, r i l c a r b o n i l o g l i c i n a m i d or, (arylcarbonyl) (alkyl) glycinamide, (monoaralkylaminocarbonyl) glycinamide, (monoaralkylaminocarbonyl) (alkyl) glycinamide, (monoarylaminocarbonyl) glycinamide, (monoarylaminocarbonyl) (alkyl) glycinamide, glycamideaminoalkyl, alaninamide, monoalkyl 1 to aninamido, alaninamide chyl, heterocyclyl and heterocyclylalkyl; heterocyclic ring system substituted by one or more substituents selected from the group consieten hydrogen, hydroxy, halo, alkyl, onyl alquilsuf, onyl arilsulf, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, haloalkoxy, alkenyl, alkynyl, aryl, aralkyl, amino, monoalkylamino, dialkylamino, monoarylamino, monoaralkylamino, alkylcarbonylamino, coxy carboni lamino, alkenyl carboni lamino, cycloalkyl carbonyl or ami no, aryl carbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbonyl) - (alkyl) amino, (alkoxycarbonyl) (alkyl) amino, alkyl sulphonylamino, aminoalkyl or, monoalkylaminoalkyl, dialkylaminoalkyl, alkylcarbonylaminoalkyl, arylocarbonylaminoalkyl, (alkylcarbonyl- (alkyl) aminoalkyl, alkoxycarbonylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, monoarylaminocarbonyl, aminocarbonylalkyl, monoalkylaminocarbonyl, alkyl dialkylaminocarbonyl, monoarylaminocarbonylalkyl, guanidino, ureido, monoalkylurethane , ureidoal quilo, monoalkylureidoalkyl and glycinamide; R4 is -0-, -N (R7) -, -C (R8) 2- or a bond; Rs is an "alkylene chain or an alkylidene chain, or if R4 is a bond, Rs is an alkylidene chain optionally substituted by aryl or -N (R7) 2; Rs 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, alkylcarbonyl, 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, cycloalkylcarbonylamino, cycloalkylalkylcarbonylamino, alkoxycarbonylaminoalkylsulfonylamino, arylcarbonylamino, and the oxycarbonyl ether il ami no (alkylcarbonyl) (alkyl) amino, aralkylcarbonylamino (aral qu ilca rb onil) (al qu il) am ino alquilcarbonilaminoal quilocicloal qu ILCA rb onyl am inoal qu iloalcoxicarbonilamin O- (alkylcarbonyl) (alkyl) aminoalkyl aralkylcarbonylamino alquiloheterociclilca onyl rb NOAL ami qu yl (aralkylcarbonyl) (alkyl) aminoalkyl onilamino arilsulf, onilaminoalquilo alquilsulf, ureido monoalquilureido, monohaloalquilureido, dialkylureido ureidoalkyl, monoalquilureidoalquilo dialquilureidoalquilo, monohaloalkylureidoalkyl aminoalkyl, monoalkylaminoalkyl dialkylaminoalkyl, carboxy 1 -alkyl or coxycarbonylalkyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl and diacylaminocarbonylalkyl; with the proviso that when R4 is -N (R7) -, Rs is an alkylene chain and R6 is -C (O) -, -C (S) - or -CH2-, R3 can not be a monocyclic ring system or saturated heterocyclic forming a bridge, comprising 4-8 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 heterocyclic ring system forming a bridge containing 4-6 members consisting of carbon atoms and two nitrogen atoms, and as a single stereoisomer or a mixture thereof; or a pharmaceutically acceptable salt thereof. The condition is set to exclude compounds described in the prior art documents. In another aspect, this invention provides pharmaceutical compositions useful for treating an inflammatory disorder - in a human in need of such treatment, which composition comprises a therapeutically effective amount of a compound of formula (Ia) as described above, and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method for treating an inflammatory disorder in a human, which method comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (la) as described above. In another aspect, this invention provides pharmaceutical compositions useful for treating an inflammatory disorder in a human in need of such treatment, which composition comprises a therapeutically effective amount of a compound of formula (Ib): wherein R2, R3, R4, R5 and R6 are the same as those described above for compounds of formula (la); and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method for treating an inflammatory disorder in a human, which method comprises administering to a human in need of such treatment, a therapeutically effective amount of a compound of formula (Ib) as described above. In another aspect, this invention provides compounds of the following formula (le): wherein R2, R3, R4, Rs and Rs are the same as those described above for compounds of formula (la); Y is a pharmaceutically acceptable counterion: RLB is one or more substituents independently selected from the group consisting of hydrogen, oxo, halo, alkyl, cycloalkyl, cycloalkylalkyl, cycloalkylaminoalkyl, (cycloalkylalkyl) amino alkyl, haloalkyl, alkenyl, alkynyl, aryl aralkyl, aralkenyl, formyl, formylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy) aralkyl, (hydroxy) cycloalkylalkyl, mercaptoalkyl, cyanoalkyl, haloalkylcarbonylaminoalkyl, (alkoxy) aralkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkylthioalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, monoarilaminoalquilo, monoaralquilaminoalquilo, alkylcarbonylaminoalkyl, (alkylcarbonyl) (alkyl) aminoalkyl, azidoalkyl, ureidoalkyl, monoalquilureidoalquilo, dialquilureido- alkyl, (alkoxycarbonylalkyl) ureidoalkyl, alcoxicarbo nilaminoalquilo, hydroxyalkylaminoalkyl, ariloxialquilcarboniloxialquilo, oxyalkyl alcoxialquilcarbonil-, aralcoxialquilcarboniloxialquilo, alkylcarbonyl, alkylcarbonylalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, aralkylcarbonyl, amino carbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, monoarilaminocarbonilo, monoaralkyl aminocarbonyl, or carboxy, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylaminocarbonyl-alkyl, onoaralkyl-aminocarbonyl-1-a, arylsulfonyl, heterocyclyl and heterocyclylalkyl; Y R9 is alkyl, aralkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkylcarbonylalkyl, alkylcarbonylaminoalkyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, heterocyclylalkyl or cycloalkylalkyl; as a single stereoisomer or a mixture thereof; or a pharmaceutically acceptable salt thereof.

In another aspect, this invention provides a pharmaceutical composition useful for treating an inflammatory disorder, which composition comprises a therapeutically effective amount of a compound of formula (le) as described above, and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method for treating an inflammatory disorder in a human, which method comprises administering to a human in need of such treatment, a therapeutically effective amount of a compound of formula (le) as described above. . In another aspect, this invention provides compounds of the following formula (Id): wherein: R3, R4, Rs and Rs are the same as those described above for compounds of formula (la); RLB is one or more substituents independently selected from the group consisting of oxo, halo, alkyl or cycloalkyl, cycl oalqui l alkyl or, cycloalkylaminoalkyl, (cycloalkylalkyl) aminoalkyl, haloalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, formyl , f-orm-alkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (Hydroxy) aralkyl, (hydroxy) cycloalkylalkyl, mercaptoalkyl, cyanoalkyl, haloalkylcarbonylamino-alkyl, (alkoxy) aralkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthioalkyl, ynyl the chyle alquilsulf, onyl alquilsulf alkyl or hydroxyalkyl thioalkyl, aminoalkyl, monoalkylamino-alkyl, dialkylaminoalkyl, monoarylaminoalkyl, monoaralkylaminoalkyl, alkylcarbonylaminoalkyl, (Alkylcarbonyl) (alkyl) aminoalkyl, azidoalkyl, ureidoalkyl, monoalquilureidoalquilo, dialkylureido-alkyl, (alkoxycarbonylalkyl) ureidoalkyl, alkoxycarbonylaminoalkyl, hydroxyalkylaminoalkyl, ariloxialquilcarboniloxialquilo, alcoxialquilcarbonil-oxyalkyl, lcoxialquilcarboniloxialquilo ar, alkylcarbonyl, alkylcarbonylalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylaminocarbonyl, dialkyl aminocarbonyl, monoarylaminocarbonyl or, monoaralkyl aminocarbonyl or, carboxy alkyl or, alkoxycarbonylalkyl, ar coxycarbonyl to chyle, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylaminocarbonyl-alkyl or, monoaralkyl aminocarbonyl alkyl, arylsulfonyl, heterocyclyl and heterocyclylalkyl; and R10 is a heterocyclyl optionally substituted by one or more substituents that are 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, monophenylalkylamino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, monophenylaminoalkyl, monophenylalkylaminoalkyl, carboxy, alkoxycarbonyl, phenylcarbonyl, benzylcarbonyl, alkylcarbonyl, carboxyalkyl , alkoxycarbonylalkyl, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, phenylaminocarbonyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylaguyl, ureido, monoalkylureido, monophenylureido and monobenzylureido, - as a single stereoisomer or a mixture thereof; or a pharmaceutically acceptable salt thereof. In another aspect, this invention provides a pharmaceutical composition useful in the treatment of an inflammatory disorder in a human in need of such treatment, which composition comprises a therapeutically effective amount of a compound of formula (Id) as described above, and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method for treating an inflammatory disorder in a human, which method comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (Id) as described above.

DETAILED DESCRIPTION OF THE INVENTION Definitions Unless specified otherwise, as used in the specification and appended claims, the following terms have the indicated meaning: "Alkyl" refers to a monovalent or divalent linear or branched radical consisting solely of carbon and hydrogen, which it contains no unsaturations and has from one to eight carbon atoms, for example, methyl, ethyl, n-propyl, 1-methylethyl, (iso-propyl), 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 wherein Ra is an alkyl radical as defined above, for example acetyl, ethylcarbonyl, n-propylcarbonyl, and the like. "Alkylcarbonylalkyl" refers to a radical of the formula -Ra-C (0) -Ra wherein each Ra is independently an alkyl radical as defined above, 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 wherein Ra is an alkyl radical as defined above, for example acetylamino, ethylcarbonylamino, n-propylcarbonylamino and the like. "(Alkylcarbonyl) (alkyl) amino" refers to a radical of the formula -N (Ra) -C (0) -Ra wherein each Ra is independently an alkyl radical as defined above, 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 (O) -Ra. Wherein each Ra is independently an alkyl radical as defined above, for example acetylaminomethyl, 2- (acetylamino) ethyl, 4- (ethylcarbonolamino) butyl and the like. "(Alkylcarbonyl) (alkyl) aminoalkyl" refers to a radical of the formula -Ra-N (Ra) -C (0) -Ra wherein each Ra is independently an alkyl radical as defined above, for example ( N-methyl-N-acetylamino) methyl, 2- (N-ethyl-N- (ethylcarbonyl) amino) propyl, and the like. "Alkylthio" refers to a radical of the formula -S-Ra wherein Ra is an alkyl radical as defined above, for example methylthio, ethylthio, N-propylthio and the like. "Alkylsulfinyl" refers to a radical of the formula -S (0) Ra wherein Ra is an alkyl radical as defined above, for example methylsulfinyl, ethylsulfinyl, n-propylsulfinyl and the like. "Alkylsulfonyl" refers to a radical of the formula -S (0) 2Ra wherein Ra is an alkyl radical as defined above, for example methylsulfonyl, ethylsulfonyl, n-propylsulfonyl and the like. "Alkylthioalkyl" refers to a radical of the formula -Ra-S-Ra wherein each Ra is independently an alkyl radical as defined above, for example methylthiomethyl, 2-methylthioethyl, 2-ethylthiopropy, and the like. "Alkylsulfinylalkyl" refers to a radical of the formula -Ra-S (0) -Ra wherein each Ra is independently an alkyl radical as defined above, for example, methylsulfinylmethyl, 2-methylsulfinylethyl, 2-ethyl-sulfinylpropyl and the like. "Alkylsulfonylalkyl" refers to a radical of the formula -Ra-S (0) 2-Ra wherein each Ra is independently an alkyl radical as defined above, for example, methylsulfonylmethyl, 2-methylsulfonylethyl, 2-ethylsulfonylpropyl and the like. "Alkylsulfonylamino" refers to a radical of the formula -N (H) -S (0) 2-Ra wherein each Ra is an alkyl radical as defined above, for example methylsulfonylamino, ethylsulfonylamino, iso-propylsulfonylamino and the like. "Alkylsulfonylaminoalkyl" refers to a radical of the formula -R »-N (H) -S (0) 2-R. wherein each R. is independently an alkyl radical as defined above, for example methylsulfonylaminomethyl, 2- (ethylsulfonylamino) ethyl, 3- (iso-propylsulfonylamino) propyl and the like. "(Alkylsulfonyl) (alkyl) minoalkyl" refers to a radical of the formula -RaN (Ra) -S (O) 2Ra wherein each Ra is independently an alkyl radical as defined above, for example (me i 1 su 1 fon) 1) (me i 1) ami n orne i 1, 2- ((ethylsulfonyl) (methyl) amino) ethyl, 3 - ((iso-propylsulfonyl) (ethyl) amino) propyl and the like. "Alkenyl" refers to a linear or branched monovalent or divalent radical consisting solely of carbon and hydrogen, containing at least one double bond and having from two to eight carbon atoms, for example, ethenyl, propyl- enyl, but-1-enyl, pent-1-enyl, penta-1,4-dienyl and the like. "Alkenylcarbonylamino" refers to a radical of the formula -N (H) -C (0) -Rc wherein Rc is an alkenyl radical as defined above, for example, ethenylcarbonylamino, prop-2-enylcarbonylamino, but-2- enylcarbonylamino and the like. "Alkynyl" refers to a straight or branched chain monovalent or divalent radical consisting solely of carbon and hydrogen, containing at least one triple bond and having two to eight carbon atoms, for example ethynyl, prop-1 -inyl, but-1-ynyl, pent-1-ynyl, pent-3-ynyl and the like. "Alkoxy" refers to a radical of the formula -0Ra where Ra is an alkyl radical as defined above, 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 (O) 0Ra wherein Ra is an alkyl radical as defined above, for example methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl and the like. "Alkoxycarbonylalkyl" refers to a radical of the formula -Ra-C (0) ORa wherein each Ra is independently an alkyl radical as defined above, for example methoxycarbonylmethyl, 2- (ethoxycarbonyl) ethyl, 2- (methoxycarbonyl) - propyl, and the like. "Alkoxyalkylcarbonyloxyalkyl" refers to a radical of the formula -Ra-OC (0) -Ra-ORa wherein each Ra is independently an alkyl radical as defined above, for example me t oxime ti 1 carboni 1 oxime ti 1 o, 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 -N (H) -C (O) -0Ra wherein Ra is an alkyl radical as defined above, for example methoxycarbonylamino, ethoxycarbonylamino, isopropoxycarbonylamino and the like. "(Alkoxycarbonyl) (alkyl) amino" refers to a radical of the formula -N (Ra) (C (O) ORa) wherein each Ra is independently an alkyl radical as defined above, for example N-met il-N-met oxycarbonylamino, N-ethyl-N-ethoxycarbonylamino and the like. "Alkoxycarbonylaminoalkyl" refers to a radical of the formula -Ra-N (H) -C (O) -ORa wherein each Ra is independently an alkyl radical as defined above, for example methoxycarbonylaminoyl, 2- (ethoxycarbonylamino) ethyl , isopropoxycarbonylaminomethyl and the like. "(Alkoxycarbonyl) (alkyl) aminoalkyl" refers to a radical of the formula -Ra-N (Ra) (C (O) OR wherein each Ra is independently an alkyl radical as defined above, for example, N-methyl -N-methoxycarbonylaminomethyl, 2- (N-ethyl) -N-ethoxycarbonylamino) ethyl and the like. "(Alkoxy) aralkyl" refers to an aralkyl radical in which the alkyl group therein is substituted by an alkoxy radical as defined above, for example, 2-phenyl-1-methoxyethyl, phenyl (methoxy) methyl, and similar.

"Alkoxyalkylcarbonylamino" refers to a radical of the formula -N (H) -C (0) -Ra-0-Ra wherein each Ra is an alkyl radical as defined above, for example methoxymethylcarbonyl amino, ethoxyethylcarbonylamino, methoxyethylcarbonylamino, and the like. "Alkoxycarbonylalkylcarbonylamino" refers to a radical of the formula -N (H) -C (O) -Ra-C (0) ORa wherein each Ra is independently an alkyl radical as defined above, for example, ethoxycarbonylmethylcarbonylamino, methoxycarbonylmethyl- carbonylamino, (2-ethoxycarbonylethyl) carbonylamino, (2-methoxycarbonylethyl) carbonylamino and the like. "Alkoxycarbonylalkylcarbonylaminoalkyl" refers to a radical of the formula -Ra-N (H) -C (O) -Ra-C (O) ORa wherein each Ra is independently an alkyl radical as defined above, for example, ethoxycarbonyl ethylcarbonylaminomethyl , 2- (methoxycarbonylmethylcarbonylamino) ethyl, 1- ((2-ethoxycarbonyl-ethyl) carbonylamino) ethyl, (2-methoxycarbonylethyl) carbonylaminomethyl and the like. "(Alkoxycarbonylalkyl) aminocarbonyl" refers to a radical of the formula -C (0) -N (H) -RaC (O) -ORa wherein each Ra is independently an alkyl radical as defined above, 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-N (H) -C (0) -N (H) -Ra-C (O) -0Ra wherein each Ra is independently an alkyl radical as defined above and wherein the nitrogen to which it binds -Ra-C (0) -0Ra is indicated as "N", for example (ethoxycarbonylmethyl) ureidometyl, (2- (ethoxycarbonyl) ethyl) Ureidomethyl, 2- ((2- (ethoxycarbonyl) ethyl) -ureido) ethyl and the like. "(Alkoxycarbonylalkylcarbonyl) (alkyl) glycinamide" refers to a radical of the formula -N (H) -C (0) -CH2-N (Ra) -C (O) -Ra-C (0) -0Ra wherein each Ra is independently an alkyl radical as defined above, for example (methoxycarbonylmethylcarbonyl) - (methyl) glycinamide, ((2-ethoxycarbonylethyl) carbonyl) (ethyl) -glycinamide and the like. "(Alkoxyalkylcarbonyl) glycinamide" refers to a radical of the formula -N (H) -C (O) -CH2-N (H) -C (0) -Ra-0-Ra wherein each Ra is independently a radical alkyl as defined above, for example, me t oxi ace i 1) gly icamido, (ethoxyacetyl) glycinamide, and the like. "Alkylene chain" refers to a branched or straight chain divalent radical consisting solely of carbonyl and hydrogen, which does not contain unsaturations and having from 1 to 8 carbon atoms, for example, methylene, ethylene, propylene, n-butylene and similar. "Alkylidene chain" refers to a branched or straight chain unsaturated divalent radical consisting solely of carbon and hydrogen atoms, having from one to eight carbon atoms, wherein the unsaturation is present only ^ Gt. as double bonds and wherein a double bond can exist between the first carbon in the chain and the rest of the molecule, for example, ethylidene, propylidene, n-butylidene and the like. "Amino" refers to the radical -NH2- "Aminoalkyl" refers to a radical of the formula -RaNH2 wherein Ra is an alkyl radical as defined above, for example aminomethyl, 2-aminoethyl, 3-aminopropyl, 2- ^ ^ 10 aminopropyl, and the like. "^ - '" Aminoalkylamino "refers to a radical of the formula -N (H) -Ra-NH2 wherein Ra is an alkyl radical as defined above, for example, aminomethylamino, (2-aminoethyl) amino, ( 2-aminopropyl) amino, and the like 15"Aminoalkoxy" refers to a radical of a formula -ORa-NH2 wherein Ra is an alkyl radical as defined above, for example aminomethoxy, 2-aminoethoxy, 3-aminopropoxy, 2- * aminopropoxy, 4-aminobutoxy and the like. "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) -NH2. "(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 define before and where the nitrogen With the substituent Ra is designated as "N", for example (aminocarbonyl) (N '-methyl) glycinamide, (aminocarbonyl) (N 1 -ethyl) glycinamide and the like. "Aminocarbonylalguilo" refers to a radical of the formula -Ra-C (0) NH2 wherein Ra is an alkyl radical as defined above, for example aminocarbonylmethyl, 2- (aminocarbonyl) ethyl, 2- (aminocarbonyl) propyl and the like . "(Aminocarbonylalkyl) aminocarbonyl" refers to a radical of the formula -C (0) -N (H) -Ra-C (0) -NH2 wherein Ra is an alkyl radical as defined above, for example, (aminocarbonylmethyl) aminocarbonyl, (2-aminocarbonylethyl) -aminocarbonyl, (1-aminocarbonylethyl) aminocarbonyl and the like. "(Aminoalkyl) aminocarbonyl" refers to a radical of the formula -C (0) -N (H) -Ra-NH2 wherein Ra is an alkyl radical as defined above, for example, (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 stated otherwise specifically herein, the term "aryl" or the prefix "ar-" (such as in "aralkyl") means to include aryl radicals optionally substituted by one or more substituents selected from the group which consists 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, monophenylalkylamino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, monophenylaminoalkyl, monofenilalquil-aminoalkyl, alkylcarbonyl, carboxy, alkoxycarbonyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonillo, monoalkylaminocarbonyl, dialkylaminocarbonyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonyl-alkyl, as defined in I presented. "Arylcarbonyl" refers to a radical of the formula -C (0) Rb wherein Rb is an aryl radical as defined above, for example, phenylcarbonyl and naphthalene-2-ylcarbonyl, and the like. "Arylcarbonylalkyl" refers to a radical of the formula -RaC (0) Rb wherein Ra is an alkyl radical as defined above, and Rb is an aryl radical as defined above, for example, phenylcarbonyl ethyl, 2- (phenylcarbonyl ) ethyl, 3- (naphthalen-2-ylcarbonyl) propyl and the like. "Arylcarbonylaminoalkyl" refers to a radical of the formula -Ra-N (H) -C (O) -Rb wherein Ra is an alkyl radical as defined above and Rb is an aryl radical as defined above, for example, (4-methoxyphenyl) carbonylaminomethyl, 2- ((4-fluorophenyl) -carbonylamino) ethyl, 1- ((4-chlorophenyl) carbonylamino) ethyl, and the like.

"Arylsulfonyl" refers to a radical of the formula -S (0) 2 -Rb wherein Rb is an aryl radical as defined above, for example, phenylsulfonyl, (4-chlorophenyl) sulfonyl, (3-nitrophenyl) sulfonyl and Similar. "Arylsulfonylamino" refers to a radical of the formula -N (H) -S (0) 2-Rb wherein Rb is an aryl radical as defined above, for example phenylsulfonylamino, (4-chlorophenyl) sulfonylamino, (4- fluorophenyl) sulfonylamino, (3-nitrophenyl) sulfonylamino) and the like. "Arylsulfonylaminoalkyl" refers to a radical of the formula -Ra-N (H) -S (0) 2 -Rb wherein Ra is an alkyl radical as defined above and Rb is an aryl radical as defined above, for example , phenylsulfonylaminomethyl, (4-chlorophenyl) sulfonylamino-methyl, 2- ((4-fluorophenyl) sulfonylamino) ethyl, 1- ((3-nitrophenyl) -sulfonylamino) ethyl and the like. "(Arylsulfonyl) (alkyl) aminoalkyl" refers to a radical of the formula -Ra-N (Ra) -S (0) 2 -Rb wherein each Ra is independently an alkyl radical as defined above and Rb is a radical aryl as defined above, for example, (phenylsulfonyl) (methyl) aminomethyl, ((4-chlorophenyl) sulfonyl) - (ethyl) aminomethyl, 2- (((4-fluorophenyl) sulfonyl) (methyl) amino) -ethyl, 1- (((3-nitrophenyl) sulfonyl) (ethyl) amino) ethyl and the like. "(Alkoxycarbonylaminoalkylcarbonyl) glycinamide" refers to a radical of the formula -N (H) -C (0) -CH2-N (H) -C (0) N (H) -C (0) -0Ra wherein Ra is an alkyl radical as defined above, 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 wherein Rb is an aryl radical as defined above, for example phenylcarbonylglycinamide , (4-fluoro-3-trifluoromethylphenyl) carbonylglycinamido, (4-fluorophenyl) carbonylglycinamide and the like. "(Arylcarbonyl) (alkyl) glycinamide" refers to a radical of the formula -N (H) -C (0) -CH2-N (Ra) -C (0) -Rb wherein Ra is an alkyl radical as defined above and Rb is an aryl radical as defined above, and the nitrogen which is attached to the radical Ra is designated as "N '", for example (phenylcarbonyl) (N'-methylglycinamide, ((4-fluoro-3-) trifluoromethylphenyl) carbonyl) - (N '-ethyl) glycinamide, ((4-fluorophenyl) carbonyl) (N * -methyl) glycinamide and the like. "Aralkyl" refers to a radical of the formula -RaRb wherein Ra is a radical alkyl as defined above and Rb is an aryl radical as defined above, for example benzyl and the like. "Aralkylcarbonyl" refers to a radical of the formula -C (0) -Rd wherein Rd is an aralkyl radical as defined before, for example benzylcarbonyl, 1- (phenyl) ethylcarbonyl and the like. "Aralkylcarbonylalkyl" refers to a radical of the formula -RaC (0) Rd wherein Ra is an alkyl radical as defined above and Rd is an aralkyl radical as defined in the foregoing, for example, benzylcarbonylmethyl, 2- (1- (phenyl) ethylcarbonyl) ethyl and the like. "Aralkenyl" refers to a radical of the formula -RcR wherein Rb is an aryl radical as defined above and Rc is an alkenyl radical as defined above, for example, 3-phenylpropyl-1-enyl and the like. "Aryloxy" refers to a radical of the formula -0Rb wherein Rb is an aryl radical as defined above, for example, phenoxy and naphthoxy, and the like. "Aralkoxycarbonyl" refers to a radical of the formula -C (0) 0Rd wherein Rd is an aralkyl radical as defined above, for example, benzyloxycarbonyl and the like. "Aralkoxycarbonylalkyl" refers to a radical of the formula -RaC (0) 0Rd wherein Ra is an alkyl radical as defined above and Rd is an aralkyl radical as defined above, for example, benzyloxycarbonylmethyl, 2- (benzyloxycarbonyl) ethyl, 3- ((naphthalen-2-yl) oxy) carbonyl) propyl and the like. "Aryloxyalkyl" refers to a radical of the formula -Ra-ORb wherein Ra is an alkyl radical as defined above and Rb is an aryl radical as defined above, for example, phenoxymethyl, 2- (phenoxy) ethyl, - (phenoxy) ropyl and the like. "Aryloxyalkylcarbonyloxyalkyl" refers to a radical of the formula -Ra-0C (0) -Ra-0Rb wherein each Ra is independently an alkyl radical as defined above and Rb is an aryl radical as defined above, for example, phenoxymethylcarbonyloxymethyl , (2-phenoxyethyl) carbonyloxymethyl, 3- ((2-phenoxyethyl) carbonyloxy) propyl and the like. "Aralkoxy" refers to a radical of the formula -0Rd wherein Rd is an aralkyl radical as defined above, for example benzyloxy and the like. "Aralkoxyalkyl" refers to a radical of the formula -Ra-0Rd wherein Ra is an alkyl radical as defined above and Rd is an aralkyl radical as defined above, for example benzyloxymethyl, 2-phenylethoxymethyl, and the like. "Aralkoxyalkylcarbonyloxyalkyl" refers to a radical of the formula -Ra-OC (O) -Ra-ORd wherein each Ra is independently an alkyl radical as defined above, and Rd is an aralkyl radical as defined above, for example, benzyloxy and ylcarbonyloxymethyl, (2- (phenyl) ethoxymethyl) -carbonyloxymethyl, 2- ((2-phenyl) ethoxymethyl) carbonyloxy) ethyl and the like. "Alkoxyalkyl" refers to a radical of the formula -RaORa wherein each Ra is independently an alkyl radical as defined above, for example methoxyethyl, ethoxymethyl, propoxymethyl, propoxyethyl, and the like. "Alaninamido" refers to a radical of the formula -N (H) -C (O) -C (CH3) H-NH2. "Alaninamidoalkyl" refers to a radical of the formula -Ra-N (H) -C (O) -C (CH 3) H-NH 2 wherein Ra is an alkyl radical as defined above, for example, alaninamidomethyl, 2- (alaninamido) ethyl, 1- (alaninamido) ethyl, 3- (alaninamido) propyl and the like. "Azidoalkyl" refers to a radical of the formula -Ra-N3 wherein Ra is an alkyl radical as defined above, for example 2-azidoethyl, 3-azidopropyl, 2-azidopropyl, 4-azidobutyl, and the like. "Benzyl" refers to a radical of the formula -CH2-Rh wherein Rh is a phenyl radical optionally substituted by one or more substituents that are 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 (O) -CH2-Rh wherein Rh is a phenyl radical as defined above, for example (4-methoxybenzyl) carbonyl, (3-fluorobenzyl) carbonyl and the like. "Carboxy" refers to a radical -C (0) OH. "Carboxyalkyl" refers to the radical of the formula -Ra-C (0) OH wherein Ra is an alkyl radical as defined above, 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 wherein Ra is an alkyl radical as defined above, for example, (carboxymethyl) aminocarbonyl, (2-carboxyethyl) aminocarbonyl, (1-carboxyethyl) aminocarbonyl and the like. "Carbicyclic ring system" refers to a stable 3- to 15-membered ring radical consisting solely of carbon and hydrogen atoms. For purposes of this invention, the radical of the carbocyclic ring system may be a monocyclic, bicyclic or tricyclic ring system and may include fused or bridged ring systems, and the ring system may be partially or fully saturated or aromatic, and the carbon atoms in the ring system optionally may be oxidized. Examples of such carbocyclic ring system radicals include, but are not limited to 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 3- to 10-membered monocyclic or bicyclic radical which is saturated and which consists solely of carbon and hydrogen atoms, for example cyclopropyl, cyclobutyl, cyclobutyl, cyclohexyl, decalinyl, and the like. Unless stated otherwise specifically in the specification, the term "cycloalkyl" means to include cycloalkyl radicals which are optionally substituted by one or more substituents independently selected 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 wherein Ra is an alkyl radical as defined above and Re is a cycloalkyl radical as defined above, for example cyclopropylmethyl, 2-cyclobutylethyl, 3-cyclohexylpropyl and Similar. "Cycloalkylamino" refers to a radical of the formula N (H) -Rβ in which Re is a cycloalkyl radical as defined above, for example, cyclopropylamino, cyclobutylamino, cyclohexylamino, and the like. "Cycloalkylamino.noalkyl" refers to a radical of the formula -Ra-N (H) -Re wherein Ra is an alkyl radical as defined above and Re is a cycloalkyl radical as defined above, for example cyclopropylaminomethyl, 2- (cyclobutylane) ethyl, cyclohexylaminomethyl and the like. "(Cycloalkylalkyl) amino" refers to a radical of the formula -N (H) -Ra-Re wherein Ra is an alkyl radical as defined above and Re is a cycloalkyl radical as defined above, for example, (cyclopropylmethyl) amino, (2-cyclobutylethyl) amino, 3- (cyclohexylpropyl) amino and the like. "(Cycloalkylalkyl) aminoalkyl" refers to a radical of the formula -Ra-N (H) -Ra-Re in which each Ra is independently an alkyl radical as defined above and Re is a cycloalkyl radical as defined above , for example, (cyclopropylmethyl) aminomethyl, 2- ((2-cyclobutylethyl) amino) ethyl, (3-cyclohexylpropyl) aminomethyl and the like. "Cycloalkylcarbonylamino" refers to a radical of the formula -C (0) -N (H) -Re in which Re is a cycloalkyl radical as defined above, for example, cyclopropylcarbonylamino, (2-phenylcyclopropyl) carbonylamino, cyclohexylcarbonylamino, 4-cyanodecalkylcarbonylamino, cyclopentylcarbonylamino and the like. "Cycloalkylcarbonylaminoalkyl" refers to a radical of the formula -Ra-C (0) -N (H) -Re wherein Ra is an alkyl radical as defined above and Re is a cycloalkyl radical as defined above, for example , cyclopropylcarbonylaminomeyl, 2- ((2-phenylcyclopropyl) carbonylamino) ethyl, 1- (cyclohexylcarbonyl-amino) ethyl, (3-phenylcyclopentyl) carbonylaminomethyl and the like. "Cycloalkylcarbonylamino" refers to a radical of the formula -C (0) -N (H) -Ra-Re wherein Ra is an alkyl radical as defined above and Re is a cycloalkyl radical as defined above, by example, (cyclopropylmethyl) carbonylamino, ((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 wherein Ra is an alkyl radical as defined above, for example cyanomethyl, 2- (cyano) ethyl, 3- (cyano) ropyl, and the like.

"DMF" refers to N, N-dimethylformamide. "DMSO" refers to dimethylsulfoxide. "Dialkylamino" refers to a radical of the formula -N (Ra) Ra wherein each Ra is independently an alkyl radical as defined above, for example, dimethylamino, methylethylamino, diethylamino, dipropylamino, ethylpropylamino and the like. "Dialkylaminoalkyl" refers to a radical of the formula -Ra-N (Ra) Ra wherein each Ra is independently an alkyl radical as defined above, for example, dimethylaminomethyl, methylethylaminomeyl, 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 above, for example, dimethylaminocarbonyl, methylethylaminocarbonyl, diethylaminocarbonyl, dipropylaminocarbonyl, ethylpropylaminocarbonyl and Similar . "Dialkylaminocarbonylalkyl" refers to a radical of the formula -Ra-C (O) N (Ra) Ra wherein each Ra is independently an alkyl radical as defined above, for example, dimethylaminocarbonylmethyl, 2- (methylethylaminocarbonyl) -ethyl, 3- (diethylaminocarbonyl) propyl, 2- (dipropylaminocarbonyl) -propyl and the like. "Dialkylaminocarbonyloxyalkyl" refers to a radical of the formula -Ra-0-C (O) -N (Ra) Ra wherein each Ra is independently an alkyl radical as defined above, for example, dimethylaminocarbonyloxymethyl, 2- ( 2- (dipropylaminocarbonyloxy) propyl, and the like, methylethylaminocarbonyloxy) ethyl, 3- (diethylaminocarbonyloxy) propyl, and the like. "Dialquilureido" refers to a radical of the formula -N (H) -C (0) -N (Ra) (Ra) or a radical of the formula -N (Ra) -C (0) -N (Ra) H wherein each Ra is independently an alkyl radical such as is defined above, and the bound 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 -N (H) -C (O) -N (Rb) (Rb) or a radical of the formula -N (Rb) -C (0) '- N (Rb) ) H wherein each Rb is independently an aryl radical as defined above, and the attached nitrogen is designated as "N", and the other nitrogen is designated as "N", for example, N ', N'-di (phenyl) ) ureido, N '-phenyl-N' - (3-nitro) phenylureido, N ', N'-di (4-methoxyphenyl) ureido, N', N '-di (4-chlorophenyl) ureido, N-4- chlorophenyl-N '- (3-chlorophenyl) ureido and the like. "Dialkylureidoalkyl" refers to a radical of the formula -Ra-N (H) -C (0) -N (Ra) (Ra) or a radical of the formula -Ra-N (Ra) -C (0) - N (Ra) H wherein each Ra is independently an alkyl radical as defined above 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 1 -methyl-N'-ethylideido) ethyl, 1- (N 1, N '-di (ethyl) ureido) ethyl, 3- (N', N'-di (propyl) ureido) propyl , 2- (N-methyl-N'-ethylureido) ethyl and the like. "Formyl" refers to a radical -C (0) H. "Formylalkyl" refers to the radical -Ra-C (0) H wherein Ra is an alkyl radical as defined above, 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 (O) -CH 2 -NH 2 wherein Ra is an alkyl radical as defined above, for example glycinemidomethyl, 2- (glycinamide) ethyl, 1- (glycinamide) ethyl, 3- (glycinamide) ropyl and the like. - "Guanidino" refers to the radical -N (H) -C (NH) -NH2. "Halo" refers to bromine, chlorine, iodine or fluorine. "Haloalkyl" refers to an alkyl radical as defined above, which is substituted by one or more halo radicals, as defined above, for example, trifluoromethyl, difluoromethyl, trichloromethyl, 2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, 3-bromo-2-fluoropropyl, 1-bromomethyl-2-bromoethyl and the like. "Haloalkoxy" refers to a radical of the formula 0Rf wherein Rf is a haloalkyl radical as defined above, for example, trifluoromethoxy, difluoromethoxy, trichloromethoxy, 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 wherein Rf is a haloalkyl radical as defined above, for example, trifluoromethylcarbonylamino, trifluoromethylcarbonylamino, 2-bromoethylcarbonylamino and the like. "(Haloalkylcarbonyl) ureido" refers to a radical of the formula -N (H) -C (0) -N (H) -C (0) -Rf wherein Rf is a haloalkyl radical as defined above, for example , (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 a radical of the formula -Ra-N (Rf) - C (O) -N (H) -Ra or a radical of the formula -Ra-N (H) -C (0) -N (Ra) Rf wherein each Ra is independently an alkyl radical as defined above and Rf is a haloalkyl radical as defined above, and the terminal nitrogen is referred to as "N, p, and the other nitrogen is designated" N ", for example, 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 -Ra-N (H) -C (0) -Rf in where Ra is an alkyl radical as defined above and Rf is a haloalkyl radical as defined above, for example, trifluoromethylcarbonylaminomethyl, 2- (trifluoromethylcarbonylamino) ethyl and the like. "Hydroxy" refers to the -OH radical. "Hydroxyalkyl" refers to to an alkyl radical as defined above which is substituted by a radical hydroxy, for 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 (O) -N (H) -Ra-OH wherein Ra is an alkyl radical as defined above, for example, hydroxymethylaminocarbonyl, (2-hydroxyethyl) aminocarbonyl, (1-hydroxyethyl) aminocarbonyl and the like. "Hydroxyalkoxy" refers to a radical of the formula -ORa-OH where Ra is an alkyl radical as defined above, for example, 2-hydroxyethoxy, 2-hydroxypropoxy, 4-hydroxybutoxy, 3-hydroxybutoxy and the like. "(Hydroxyalkoxy) carbonyl" refers to a radical of the formula -C (0) 0H -0Ra-where Ra is an alkyl radical as defined above, 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 above 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 alkylthioalguyl radical as defined above which is substituted by a hydroxy radical, for example, 2-hydroxyethylthiometyl, 2- (hydroxymethylthio) ethyl, and the like. "Hydroxyalkenyl" refers to an alkenyl radical as defined above which is substituted by a hydroxy radical, e.g., 3-hydroxyprop-l-enyl, 4-hydroxybut-l-enyl, 4-hydroxypent-1-enyl, 5- hydroxypenta-l, 3-dienyl and the like. "Hydroxyalkynyl" refers to an alkynyl radical as defined above which is substituted by a hydroxy radical, for example, 3-hydroxypropyl, 4-hydroxypent-2-ynyl, 1-hydroxybut-3-ynyl and the like. "(Hydroxy) cycloalkylalkyl" refers to a radical of the formula -Ra (0H) -Re wherein Ra is an alkyl radical as defined above and Re is a cycloalkyl radical as defined above, and wherein the OH radical is a substituent on any carbon of the radical Ra, for example, 2-cyclopropyl-l-hydroxyethyl, (4-hydroxycyclohexyl) methyl and the like .. "Hydroxyalkylaminoalkyl" refers to a monoalkylaminoalkyl radical as defined above which is substituted by a hydroxy radical , for example, 2-hydroxyethylaminomethyl, 2- (3-hydroxypropylamino) ethyl and the like.

"Hydroxyamidino" refers to a radical of the formula -C (NH2) = NOH. "Heterocyclic ring system" refers to a stable 3- to 15-membered ring radical, which consists of carbon atoms and 1 to 5 heteroatoms that are selected from the group consisting of nitrogen, oxygen and sulfur. For purposes of this invention, the heterocyclic ring system radical can be a monocyclic, bicyclic or tricyclic ring system, which can include fused or bridged ring systems; and the nitrogen, carbon or sulfur atoms in the heterocyclic ring system radical optionally may be oxidized; the nitrogen atom may optionally be quaternized; and the heterocyclic ring system may be partially or completely saturated or aromatic. The heterocyclic ring system can be attached to the main structure at any heteroatom or carbon atom which results in the creation of a stable compound. Examples of such heterocyclic radicals include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl, carbazolyl, cinolinyl, decahydroisoquinolyl, dioxolanyl, furanyl, isothiazolyl, quinuclidinyl, imidazolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, indolyl, insoindolyl, 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, quinazolinyl, quinoxalinyl, Quinolinyl, quinuclidinyl, isoquinolinyl, triazolyl, thiazolidinyl, thiadiazolyl, thiazolyl, tetrazolyl, tetrahydrofuryl, triazinyl, tetrahydropyranyl, thienyl, thiamorpholinyl, thiamorpholinyl sulfoxide thiamorpholinyl sulfone. "Heterocyclyl" refers to a heterocyclic ring system as defined above. Unless stated otherwise specifically the specification, the term "heterocyclyl" means include a heterocyclic ring system as defined above which is optionally substituted by one or more .sustituyentes 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 , monofenilalquil-amino, aminoalkyl, mon or 1 qu i 1 ami noa 1 qu i 1 or dialkylaminoalkyl, monophenylaminoalkyl, monofenilalquil-aminoalkyl, carboxy, alkylcarbonyl, phenylcarbonyl, benci 1 carbonyl, alkylcarbonyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonyl, monoalquilcarbonilo, dialkylaminocarbonyl , phenylaminocarbonyl, aminocarbonylalkyl, monoalkylamino carbonylalkyl, dialkylaminocrbonyl-alkyl, ureido, onoalkylureido, monophenylureido, monobenzylureido, as defined herein. "Heterocyclylalkyl" refers to a radical of the formula -RaRg where Ra is an alkyl as defined above and Rg is a heterocyclyl radical radical as defined above, eg, indolinylmethyl or imidazolylmethyl, and the like. "Heterocyclylamino" refers to a radical of the formula -N (H) -Rg wherein Rg is a heterocyclyl radical as defined above, for example, oxazol-2-ylamino; piperidin-4-ylamino and the like. "Heterocyclylaminoalkyl" refers to a radical of the formula Ra-N (H) -Rg where Ra is an alkyl radical as defined above and Rg is a heterocyclyl radical as defined above, for example oxazol-2-ylaminomethyl, - (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 wherein Rg is a heterocyclyl radical as defined above, for example, piperidin-4-ylcarbonylamino, furan-2-ylcarbonylamino; morpholin-4-ylcarbonylamino; and similar. "Heterocycliccarbonylaminoalkyl" refers to a radical of the formula -Ra-N (H) -C (0) -Rg wherein Ra is an alkyl radical as defined above and Rg is a heterocyclyl radical as defined above, for example, piperidin-4-ylcarbonylaminomethyl, 2- (furan-2-ylcarbonylamino) ethyl, 1- (morpholin-4-ylcarbonylamino) -ethyl and the like. _ "Mercapto" refers to the radical -SH. "Mercaptoalkyl" refers to a radical of the formula -Ra-SH wherein Ra is an alkyl radical as defined above, for example mercaptomethyl, 2-mercaptoethyl, 3-mercaptopropyl, 2-mercaptobutyl and the like. "Monoalkylamino" refers to a radical of the formula -N (H) Ra wherein Ra is an alkyl radical as defined above, for example, methylamino, ethylamino, propylamino and the like. "Monoalkylaminoalkyl" refers to a radical of the formula Ra-N (H) Ra wherein each Ra is independently an alkyl radical as defined above, for example, methylaminomethyl, ethylaminomethyl, 2- (propylamino) ethyl and the like. "(Monoalkylamino) aralkyl" refers to a radical of the formula -Rd-N (H) Ra wherein Ra is an alkyl radical as defined above and Rd is an aralkyl radical as defined above, 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) Rb wherein Rb is an aryl radical as defined above, for example phenylamino, (4-methoxyphenyl) amino, (3,4,5-trimethoxyphenyl) - amino and similar. "Monoarylaminoalkyl" refers to a radical of the formula -Ra-N (H) Rb wherein Ra is an alkyl radical as defined above and Rb is an aryl radical as defined above, 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 wherein Rd is an aralkyl radical as defined above, for example, benzylamino, (3, 4, 5-trimethoxybenzyl) amino, 4- (chlorobenzyl) amino and similar. "Monoaralkylaminoalkyl" refers to a radical of the formula -Ra-N (H) Rd where Ra is an alkyl radical as defined above and Rd is an aralkyl radical as defined above, for example, benzylaminomethyl, (3-phenylpropyl) aminomethyl, 2- (benzylamino) ethyl and the like. "Monoalkylaminocarbonyl" refers to a radical of the formula -C (0) N (H) Ra wherein Ra is an alkyl radical as defined above, for example methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl and the like.

"Monoalkylaminocarbonylalkyl" refers to a radical of the formula -Ra-C (O) N (H) Ra wherein each Ra is independently an alkyl radical as defined above, for example methylaminocarbonylmethyl, 2- (ethylaminocarbonyl) ethyl, 3- (propylaminocarbonyl) propyl and the like. "Monoarylaminocarbonyl" refers to a radical of the formula -C (0) N (H) Rb wherein Rb is an aryl radical as defined above, for example, phenylaminocarbonyl, (3,4,5-tris (trifluoromethoxy) phenyl aminocarbonyl, (4-chlorophenyl) -aminocarbonyl and the like. "Monoarylaminocarbonylalkyl" refers to a radical of the formula -Ra-C (O) N (H) Rb wherein Ra is an alkyl radical as defined above and Rb is an aryl radical as defined above, for example, phenylaminocarbonylmethyl, 2- ((4-chlorophenyl) amino-carbonyl) ethyl, 3- ((3,4,5-trimethoxyphenyl) aminocarbonul) ropyl and the like. "Monoaralkylaminocarbonyl" refers to a radical of the formula -C (0) N (H) Rd wherein Rd is an aralkyl radical as defined above, for example benzylaminocarbonyl, (3,4,5-tris (triforor orne t oxy) benz i 1) amino c arboni 1 or, (4-chlorobenzyl) aminocarbonyl and the like. "Monoaralkylaminocarbonylalkyl" refers to a radical of the formula -Ra-C (O) N (H) Rd wherein Ra is an alkyl radical as defined above, and Rd is an aralkyl radical as defined above, for example, benzylaminocarbonylmethyl , 2- ((4-chlorobenzyl) aminocarbonyl) ethyl, 3- ((3,4,5-trimethoxybenzyl) -aminocarbonyl) propyl and the like. "(Monoalkylaminocarbonylalkyl) aminocarbonyl" refers to a radical of the formula -C (0) -N (H) -Ra-C (O) -N (H) Ra wherein each Ra is independently an alkyl radical as defined above , for example (methylaminocarbonylmethyl) -aminocarbonyl, (2- (me-ylaminocarbonyl) ethyl) aminocarbonyl, (1- (ethylaminocarbonyl) tyl) aminocarbonyl and the like. "Monoalkylalaninamide" refers to a radical of the formula -N (H) -C (0) -C (CH 3) HN (H) Ra wherein Ra is an alkyl radical as defined above and the attached nitrogen is designated as " N "and the other nitrogen (which has the substituent Ra) is designated as" N '", for example N '-methylalanimido, N' -ethylalanimido and the like. "Monoalkylglycinamido" refers to a radical of the formula -N (H) -C (0) -CH2-N (H) Ra wherein Ra is an alkyl radical as defined above and the attached nitrogen is designated as "N" and the other nitrogen (which has the subsent Ra) is designated as "N '", for example N' -methylglycinamide, N'-ethylglycinamide and the like. "(Monoarylaminocarbonyl) glycinamide" refers to a radical of the formula -N (H) -C (0) -CH2-N (H) -C (0) -N (H) Rb wherein Rb is an aryl radical such as is defined above, for example, ((4-phenoxyphenyl) aminocarbonyl) glycinamide, ((4-chlorophenyl) amidocarbonyl) glycinamide, (phenylaminocarbonyl) glycinamide and the like. "(Monoarylaminocrbonyl) (alkyl) glycinamide" refers to a radical of the formula -N (H) -C (0) -CH2-N (Ra) -C (0) -N (H) Rb wherein Ra is a alkyl radical as defined above and Rb is an aryl radical as defined above, and the nitrogen to which Ra is attached is designated as "N '", for example ((4-phenoxyphenyl) -aminocarbonyl) (N 1 -methyl) glycinamide , ((4-chlorophenyl) aminocarbonyl) (N * -ethyl) glycinamide, (phenylaminocarbonyl) (N'-methyl) glycinamide and the like. "(Monoaralkylaminocarbonyl) glycinamide" refers to a radical of the formula -N (H) -C (0) -CH2-N (H) -C (0) -N (H) Rd wherein Rd is an aralkyl radical such as is defined above, 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 (0) -N (H) Rd wherein Ra is a alkyl radical as defined above and Rd is an aralkyl radical as defined above, and the nitrogen to which Ra is attached is referred to as "N '", for example, ((4-phenoxybenzyl) aminocarbonyl) (N' -met ) glycinamide, ((4-chlorobenzyl) minocarbonyl) (N 1 -ethyl) glycinamide, (benzylaminocarbonyl) (N 1 -methyl) glycinamide and the like.

"Monoalkylureido" refers to a radical of the formula -N (H) -C (0) -N (H) Ra or a radical of the formula -N (Ra) -C (0) -NH2 where Ra is a radical alkyl as defined above and the bound nitrogen is designated as "N", and the other nitrogen is designated "N '", for example, N' - ethylureudo, N1 -ethylureido, N '-propylureido, N-methylureido, N -ethylurid, N-propylureido and the like. "Monofenilureido" refers to a radical of the formula -N (H) -C (O) -N (H) Rh wherein Rh is a phenyl radical as defined above, and the nitrogen to which it is attached is designated as "N", and the other nitrogen is designated as " N '", for example, N' -phenylureido, N '- (4-nitrophenyl) ureido, N 1 - (3-chlorophenyl) ureido and the like. "Monobenzylureide" refers to a radical of the formula -N (H) -C (O) -N (H) -CH2-Rh wherein Rh is a phenyl radical as defined above, and the nitrogen to which it is attached is designates as "N", and the other nitrogen is designated "N '", for example, N' -benzylureide, N '- (4 - nor t robenzyl) ureido, N' - (3-chlorobenzyl) ureido and the like . "Monohaloalkylureido" refers to a radical of the formula -N (H) -C (0) -N (H) Rf or a radical of the formula -N (Rf) -C (0) -NH2 wherein Rf is a haloalkyl radical as defined above, and the attached nitrogen is designated as "N, p, and the other nitrogen is designated as" N1", for example, N '-chloromethylureide, N' - (2,2-difluoroethyl) ureido, N '- (3-chloropropyl) ureido, N- (t-fluoromethyl) 1-ureido, N- (pentafluoroethyl) ureido, N- (3-iodopropyl) ureido and the like. "Mono-arylureide" refers to a radical of the formula -N (H) -C (0) -N (H) Rb or a radical of the formula -N (Rb) -C (O) -NH2 wherein Rb is an aryl radical as defined above, and the nitrogen attached is designated as "N" and the other nitrogen is designated as "N '", for example, N' -phenylureido, N '- (4-methoxyphenyl) ureido, N' - (3-chlorophenyl) ureido, N-phenylureido, N- (2-trifluoromethylphenyl) -ureido, N- ( 4-chlorophenyl) ureido and the like. "Monoaralguilureido" refers to a radical of the formula -N (H) -C (O) -N (H) Rd a radical of the formula -N (Rd) -C (O) -NH2 wherein Rd is an aralkyl radical as defined above, and the attached nitrogen is designated "N" "and the other nitrogen is designated" 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 -N (Ra) -C (0) -N (Rb) H, or a radical of the formula -N (Rb) -C (0) -N (Ra) H, or a radical of the formula -N (H) -C (O) -N (Ra) (Rb) wherein Ra is an alkyl radical as defined above, and Rb is an aryl radical such as defined above, and wherein the bound nitrogen is designated "N", and the other nitrogen is designated "N '", for example, N-methyl-N1-phenylureido, N-phenyl-N' -ethylureido, N- methyl-N '- (4-fluorophenyl) ureido, N 1 -ethyl-N' - (3-cyanophenyl) ureido and the like. "Monoalkylureidoalkyl" refers to a radical of the formula -Ra-N (H) -C (O ) -N (H) to a radical of l to formula -Ra-N (Ra) -C (0) -NH2 wherein Ra is an alkyl radical as defined above, and the nitrogen to which it is attached is designated as "N" and the other nitrogen is designated as "N" '", for example, N' -methylureidomethyl, 2 - (N '- et illure) et il or, 1- (N'-propylureido) ethyl, N-methylureidomethyl, 2- (Ne.ethylureido) ethyl , 1- (N-propylureido) ethyl and the like. "Monohaloalkylureidoalkyl" refers to a radical of the formula -Ra-N (H) -C (O) -N (H) Rf or a radical of the formula -Ra-N (Rf) -C (0) -NH2 wherein Ra is an alkyl radical as defined above, and Rf is a haloalkyl radical as defined above, and the attached nitrogen is designated as "N", and the another nitrogen is designated as "N, M, for example 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-iodopropyl) ureido) ethyl and the like. "Monoarylureidoalkyl" refers to a radical of the formula -Ra-N ( H) -C (O) -N (H) Rb or a radical of the formula -Ra-N (Rb) -C (0) -NH2 wherein Ra is an alkyl radical as defined above and Rb is an aryl radical as defined above, and the attached nitrogen is designated as "N" and the other nitrogen is designated as "N, M, for example, N '-phenylureidomethyl, 2- (N' - (4-methoxyphenyl) ureido) ethyl, 1- (N '- (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-N (H) -C (O) -N (H) Rd or a radical of the formula -Ra-N (Rd) -C (O) -NH2 wherein Ra is an alkyl radical as defined above and Rd is an aralkyl radical as defined above , and the bound nitrogen is designated "N", and the other nitrogen is designated "N1", for example, 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 simi lares. "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 example benzylamino, 2- (benzyl) butylamino and the like. "Monophenylanoalkyl" refers to an alkyl radical as defined above substituted by a monophenylamino group as defined above, for example (phenylamino) methyl, 2- (1- (phenyl) ethylamino) ethyl and the like. "Monophenylalkylaminoalkyl" refers to an alkyl radical as defined above substituted by a monophenylalkylamino group as defined above, for example, (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 event of circumstances described subsequently may or may not occur, and that the description includes cases in which the event or circumstance occurs and cases in which this does not occur. For example, "optionally substituted aryl" means that the aryl radical may or may not be substituted and that the description includes substituted aryl radicals and aryl radicals without substitution. "Phenyl" refers to the benzene radical optionally substituted by one or more substituents that are selected from the group consisting of hydroxy, halo, alkyl, haloalkyl, alkoxy, alkenyl, nitro, cyano, amino, aminoalkylamino, dialkylamino, alkylcarbonyl, carboxy, alkoxycarbonyl and aminocarbonyl. "Phenoxy" refers to the radical of the formula -0Rh where Rh is phenyl as defined above. "Phenylalkyl" refers to an alkyl radical as defined above substituted by a phenyl radical, for example, benzyl, and the like.

"Phenylalkenyl" refers to an alkenyl radical as defined above substituted by a phenyl radical, for example, 3-phenylprop-2-enyl and the like. "Phenylalkoxy" refers to a radical of the formula -ORÍ wherein R ± is a phenylalkyl radical as defined above, for example, benzyloxy, and the like. "Phenylalkoxyalkyl" refers to an alkyl radical as defined above substituted by a phenylalkoxy radical as defined above, for example, benzyloxymethyl, and the like. "Phenylcarbonyl" refers to a radical of the formula -C (0) -Rh wherein Rh is a phenyl radical as defined above, for example, (4-chlorophenyl) carbonyl, (4-fluorophenyl) carbonyl and the like. "Phenylaminocarbonyl" refers to a radical of the formula -C (O) -N (H) -Rh wherein Rh is a phenyl radical as defined above, for example, (4-chlorophenyl) aminocarbonyl, (4-methoxyphenyl) aminocarbonyl and the like. "Pharmaceutically acceptable counterion" refers to those anions which retain the biological effectiveness and properties of the original compound, which are not biologically or otherwise undesirable. Examples of such anions can be found in Berge, S.M. et al., Journal of Pharmaceuticals Sciences (1977), Vol. 66, No. 1, pp. 1-19.

"Pharmaceutically acceptable salt" includes addition salts of both acid and base. "Pharmaceutically acceptable acid addition salt" refers to those salts which retain the biological effectiveness and properties of the free bases, which are not biologically or otherwise undesirable, and which are formed with inorganic acids such as acid hydrochloric, hydrobromic 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. "Pharmaceutically acceptable base addition salt" refers to those salts which retain their biological effectiveness and properties of the free acids, which are not biologically undesirable or in some other way. These salts are prepared from the addition of an inorganic base or an organic base to a free acid. Salts derived from inorganic bases include, but are not limited to, the sodium, potassium, lithium, ammonium, calcium, magnesium, zinc, aluminum and the like salts. The preferred inorganic salts are the ammonium, sodium, potassium, calcium and magnesium salts. Salts derived from organic bases include, but are not limited to, primary, secondary and tertiary amine salts, substituted amines including naturally occurring substituted amines, 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 -ethyl-piperidine, polyamine resins and the like. Particularly preferred are the organic bases of isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline and caffeine. "THF" refers to tetrahydrofuran. "Therapeutically effective amount" refers to a quantity of a compound of formula (I) which, when administered to a human in need of such administration, is sufficient to carry out the treatment as defined below, for inflammatory disorders the which are alleviated by the inhibition of the activity of the chemokines, in particular MlP-la and RANTES, for inflammatory disorders characterized by migration, accumulation and activation of leukocytes to the affected tissue. The amount of a compound of formula (I) which constitutes a "therapeutically effective amount" will vary depending on the compound, the disorder and its severity, and the age of the human, which is treated, but can be determined systematically by a person usually familiar with the technique when considering their own knowledge and based on this description. "Treat" or "treatment" as used herein encompasses the treatment of an inflammatory disorder in a human, and includes: (i) preventing the disorder from occurring in a human, particularly when such a human is predisposed to the disorder but He has not yet been diagnosed as suffering from it; (ii) inhibit the disorder, that is, suppress its development; or (iii) alleviating the disorder, that is, causing the regression of the disorder. "Ureido" refers to a radical of the formula -N (H) -C (O) -NH2. "Ureidoalkyl" refers to a radical of the formula -Ra-N (H) C (O) NH 2 wherein Ra is an alkyl radical as defined above, for example ureidomethyl, 2- (ureido) ethyl, 3- (ureido) ) ropilo and the like. It is understood from the above definitions and examples that for radicals containing a substituted alkyl group, any substitution therein can occur on any carbon of the alkenyl group. The compounds of the invention or their pharmaceutically acceptable salts, they may have an asymmetric carbon in their structure. The compounds of the invention and their pharmaceutically acceptable salts can therefore exist as single stereoisomers, racemates and as mixtures of enantiomers and diastereomers. All of such stereoisomers, racemates and mixtures thereof are intended to be within the scope of this invention. The absolute configuration of certain carbon atoms within the compounds, if known, is indicated by the appropriate absolute description R or S. The term "trans" is used to indicate that the Rla or Rlb substituents are on opposite sides of the piperazine plane. The term "cis" is used to indicate that the Rla or Rlb substituents are on the same side of the piperazine plane. The nomenclature used herein is a modified form of the I.U.P.A.C. system. wherein the compounds of the invention are named as piperazine derivatives. For example, a compound of formula (la) wherein R6 is -C (O) -, R5 is ethylene, R4 is -O-, Rla is in the 2-position to the piperazine ring and is ethoxycarbonyl, R2 is 2- (ethylamino) ethyl at the 4-position of the phenyl ring and R3 is naphthalene-1-yl substituted at the 4-position by methoxy, ie, the compound of the following formula: it is referred to herein as 1- (2- ((4-methoxynaphthalen-1-yl) oxy) ethyl) carbonyl-2-ethoxycarbonyl-4 - (4 - (2 - (ethylamino) ethyl) benzyl) piperazine.

Utility and Administration Utility The compounds of the invention inhibit the activity of the MlP-la and RANTES chemokines and are therefore useful as anti-inflammatory agents. In particular, the compounds are useful for treating inflammatory disorders such as multiple sclerosis, leukoencephalopathy, encephalomyelitis, Alzheimer's disease, Guilian-Barre syndrome, acute rejection of cell-mediated renal transplantation, allograft rejection, rheumatoid arthritis, atherosclerosis, urticaria, angioderma, allergic conjunctivitis, atopic dermatitis, allergic contact dermatitis, drug allergy or insect bite or systemic anaphylaxis. Of particular interest for the invention is the use of the compounds to treat multiple sclerosis.

B. Tests To demonstrate that the compounds inhibit the activity of MlP-la or RANTES, various assays can be used. One trial uses a microphysiometer, which uses a patented, silicon-based, light-addressable potentiometric sensor to continuously monitor underlying changes at extracellular pH levels. These changes result from the generation of acid metabolites excreted by living cells to their immediate microenvironment during basal and stimulated conditions. It has been previously demonstrated by microphysiometry that THP-1 cells, which have been shown to express the chemokine receptors CCR1 and CCR2, respond in a dose-related manner to their respective chemokines, which include MlP-la, RANTES and MCP -1 (a ligand for CCR2). See, for example Hirst, M. et al., "Chemokine receptors" Journal of NIH Research (1995) Vol. 80. Another assay which can be used to demonstrate the ability of the compounds to inhibit MlP-la activity and RANTES is based on the measurement of intracellular Ca2 + concentrations and / or increases in the release of intracellular [3H] inositol phosphatase from cells stimulated with MlP-la and RANTES. The binding of ligand to the CCR1 receptor results in activation induced by G protein of phospholipase C, which leads to the conversion of phosphatidylinositol phosphate to inositophosphate and diacylglycerol. In turn, inositol phosphate binds to a receptor located at intracellular sites to release Ca2 + in the cytoplasm. In addition to the increases in Ca + concentration due to the release of intracellular stores, the binding of inositol phosphate to its receptor leads to an increased flow of extracellular calcium through the membrane and into the cell. Therefore, activation of the CCR1 receptor by MlP-la and RANTES and, subsequently, inhibition of activation by the compounds of the invention can be determined by testing an increase in free intracellular Ca2 + concentrations. Typically this can be accomplished by the use of calcium-sensitive fluorescent probes such as quin-2, fura-2- and indo-1. Alternatively, activation or functional inhibition of CCR1 receptor activation can be measured by quantitation of [3 H] inositol phosphate release from cells previously 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-la and RANTES by competitive binding to the receptor). See, for example, Neote, K. et al., Cell (1993), Vol. 72. pp. 415-425. A particular assay employs the use of HEK293 cells which have been stably transfected to express the human CCR1 receptor. The standard in vivo assays which can be used to demonstrate the usefulness of the compounds as anti-inflammatory agents are the animal model for the experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis and the adjuvant-induced arthritis (AIA) model for arthritis. rheumatoid 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 accepted modes of administration or agents to provide similar utility. Therefore, the administration can be, for example, orally, nasally, parenterally, topically, transdermally or rectally, sublingually, intramuscularly, subcutaneously or intravenously, in the form of a solid, semi-solid, lyophilized powder or in forms of Liguid dosage, such as for example tablets, suppositories, pills, elastic and hard soft gelatin capsules, powders, solutions, suspensions or aerosols, or the like, preferably in unit dosage forms suitable for simple administration of precise dosages. The compositions will include a conventional pharmaceutical carrier or excipient and a compound of the invention as the active agent, and may also include other medicinal agents, pharmaceutical agents, carriers, adjuvants, etc. Generally, based on the mode of administration proposed, the pharmaceutically acceptable composition will contain about 1% to about 99% by weight of the compound or compounds of the invention, or a pharmaceutically acceptable salt thereof, and 99% to 1% by weight of one or more pharmaceutically suitable excipients. Preferably, the composition will constitute about 5% to 75% by weight of the compound or compounds of the invention, or a pharmaceutically acceptable salt thereof, the remainder consisting of suitable pharmaceutical excipients. The preferred route of administration is oral, through the use of a convenient daily dosage regimen which can be adjusted according to the degree of severity of the disease state in question. For such oral administration, a pharmaceutically acceptable composition containing the compound or compounds of the invention, or a pharmaceutically acceptable salt thereof, is constituted by the incorporation of any of the commonly used excipients. Such excipients include non-toxic, chemically compatible fillers, binders, disintegrants, preservatives, preservatives, antioxidants, lubricants, flavors, thickeners, coloring agents, emulsifiers and the like, for example, pharmaceutical grades of mannitol, lactose, starch, pregelatinized starch, magnesium stearate, sodium saccharin, talc, cellulose ether derivatives, glucose, gelatin, sucrose, citrate, cyclodextrin, propyl gallate and the like. Such compositions take the form of solutions, suspensions, tablets, pills, capsules, powders, sustained release formulations and the like. Preferably such compositions will take the form of capsules, caplet (capsule-shaped) or tablet and will therefore also contain a diluent such as lactose, sucrose, dicalcium phosphate and the like; a disintegrant such as sodium croscamellose or derivatives thereof, a lubricant such as magnesium stearate and the like, and a binder such as starch, acacia gum, polyvinyl pyrrolidone, gelatin, cellulose ether derivatives and the like. The compounds of the invention, or their pharmaceutically acceptable salts, can also be formulated in a suppository using, for example, about 0.5% to about 50% active ingredient placed in a carrier that dissolves slowly within the body, for example polyoxyethylene glycols and polyethylene glycols (PEG), for example PEG 1000 (96%) and PEG 4000 (4%) and propylene glycol.

The pharmaceutically administrable liquid compositions can be prepared, for example, by dissolving, dispersing, etc., a compound or compounds of the invention (about 0.5% to about 20%) or a pharmaceutically acceptable salt thereof, and optional pharmaceutical adjuvants in a carrier, such as, for example, water, saline, aqueous dextrose, aqueous cyclodextrin, glycerol, ethanol and the like, to thereby form a solution or suspension. If desired, a pharmaceutical composition of the invention may also contain minor amounts of auxiliary substances, such as wetting agents or emulsifiers, pH buffering agents, antioxidants and the like, such as, for example, citric acid, sorbitan monolaurate, oleate triethanolamine, butylated hydroxytoluene, etc. Current methods for preparing such dosage forms are known, or will be apparent to those familiar in this art, - for example, see Remington's Pharmaceutical Sciences, 18th Ed., (Mack Publishing Company, Easton, Pennsylvania, 1990). The composition to be administered, in any case, will contain a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof, for treatment of an inflammatory disorder alleviated by the inhibition of chemokine activity, MIP. -la and RANTES.

The compounds of the invention, or their pharmaceutically acceptable salts, are administered in a therapeutically effective amount which will vary based on various factors including the activity of the specific compound used, metabolic stability and duration of action of the compound, age, body weight, general health, sex, diet, mode and time of administration, speed of excretion, combination with other medications, the severity of the particular disease states and the therapy under which the host is. Generally, a therapeutically effective daily dose 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 pharmaceutically acceptable salt thereof, - preferably, from about 0.14 mg to about 10.0 mg / kg of body weight per day, more preferably, from about 1.4 mg to about 7.0 mg / kg of body weight per day. For example, for administration to a 70 kg person, the dosage range will be from about 1.0 mg to about 1.0 grams per day of a compound of the invention, or a pharmaceutically acceptable salt thereof, preferably from about 10 mg to about 700 mg per day, and more preferably from about 100 mg to about 500 mg per day.

Preferred Modalities One aspect of the invention are compounds of formula (Ia) as defined in the above in the Brief Description of the Invention. Of these compounds, a preferred group of compounds of formula (a) "" is that group of compounds wherein: R3 is a carbocyclic ring system substituted by one or more substituents that are independently selected from the group consisting of hydrogen, hydroxy , hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, arylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, hydroxyalkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, aminoalkoxy, cycloalkyl , cycloalkylalkyl, (hydroxy) cycloalkylalkyl, cycloalkylamino, inoalquilo cycloalkylated, "cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy) aralkyl, (monoalkylamino) aralkyl, (hydroxyalkyl) hyalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy) aralkyl, aryloxyalkyl, aralkoxyalkyl, amino, monoalkylamino, dialkylamino, monoarylamino, monoaralkylamino, aminoalkylamino, heterocyclylamino, (cycloalkylalkyl) amino, alkylcarbonylamino, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonyl-amino, haloalkylcarbonylamino, alkoxyalkylcarbonyl- amino, to the carbonyl to the 1-carbonyl amino, (Alkylcarbonyl) (alkyl) amino, (alkoxycarbonyl) - (alkyl) amino, onilamino alquilsulf, aminoalkyl, monoalkyl aminoalkyl, dialkylaminoalkyl, hydroxyalkyl aminoalkyl, monoaryl aminoalkyl, monoaralquilaminoalquilo, alkylcarbonylaminoalkyl, ar yl carbonylaminoalkyl, (alkylcarbonyl) - (alkyl) aminoalkyl, (cycloalkyalkyl) aminoalkyl, coxy carbonyl aminoalkyl, coxycarbonyl alkylcarbonylaminoalkyl, (alkoxycarbonyl) (alkyl) -aminoalkyl, alkylsulfonyl aminoalkyl, (Onil alquilsuf) (alkyl) aminoalkyl, onilaminoalquilo arilsulf, (onil arilsuf) (alkyl) aminoalkyl, heterocyclylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, (hydroxyalkoxy) carbonyl, carboxyalkyl, alkoxycarbonylalkyl, to ral coxi carbonyl alkyl or at coxi carb onyl alkyl -oxy the chyle, dialquilaminocarboniloxialquilo, alkylcarbonylalkyl, arylcarbonylalkyl, aralquilcarbonilalquilo, aminocarbonyl, mono alkylaminocarbonyl, dialkylaminocarbonyl, monoarilaminocarbonilo, monoaralkylaminocarbonyl, (aminocarbonylalkyl) aminocarbonyl, (monoalkyl-aminocarbonylalkyl) aminocarbonyl, (carboxyalkyl) -aminocarbonyl, (alkoxycarbonylalkyl) aminocarbonyl, (aminoalkyl) aminocarbonyl, (hydroxyalkyl) aminocarbonyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylaminocarbonylalkyl, monoaralkylaminocarbonylalkyl, amidino, hydroxyamidino, guanidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, monohaloalkylureido, (Monoalkyl) (monoaryl) ureido, dialkylureido, diar i lur eido, (hal oalqu yl carboni 1) ure gone, ureidoalkyl, monoalquilureidoalquilo, dialquilureidoalquilo, monoarilureidoalquilo, monoaralquiiureidoalquilo, monohaloalquilureidoalquilo, (hal oal qu yl) (to qu yl) ure i the alkyl, (alkoxycarbonylalkyl) ureidoalkyl, glycinamide, monoalkylglycinamido, aminocarbonylglycinamido, (Oxi c to qu ilc arb oni l) gl ic Inami do, (amino c Arboni l) (alkyl) gl ic inamido, (alcoxicarbonilalquilcarbonil) (alkyl) glycinamido, (alcoxicarbonilaminoalquilcarbonil) glycinamido, arilcarbonilglicinami do, (ar yl carb oni l) (al qu il) gl ici nami do, (monoaralkylaminocarbonyl) glycinamide, (monoaralkylaminocarbonyl) (alkyl) glycinamide, (monoari l aminocarboni l) gl icamido, (monoaryl aminocarbonyl) (alkyl) glycinamide, glycinamidoalkyl, alaninamide, monoalkylalaninamide, 1 to 1 ammonium, heterocyclyl and heterocyclylalkyl. Of this group of compounds, a preferred subgroup of compounds is that group of compounds wherein: R4 is -0-, -N (R7) - or -C (R8) -; Rs is an alkylene chain; R7 is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralquilcarbonilalquilo, 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 alkyl, ino cicloalquilcarbonilam, cicloalquilalquilcarbonilamino, alkoxycarbonylamino, alquilsufonilamino, arylcarbonylamino, the c oxy carboni lal qu ilca rb on il ami no, (alkylcarbonyl) (alkyl) amino, aralkylcarbonylamino, (R to l qu i l c a rb o n i l) (a l qu i l) am i n o, a l q u i l c a r b o n i l a m i n or l q u i l o, c i c l o a l qu i l c a r b o n i l am i n or l qu i l o, a l c or x i c a r b o n i l a m i n or l q u i l o, (alkylcarbonyl) (alkyl) aminoalkyl, a r a l i c a c a r b o n i l a m a n i a l a l a l, h e t e r o c i c l i i i i i i i i i i i i i i i i i i o (aralkylcarbonyl) (alkyl) aminoalkyl, arylsulphonylamino, alkylsulphonylaminoalkyl, ureido, monoalkylureido, monohaloalkylureido, dialkylureido. ureidoalkyl, monoalquilureidoalquilo, dialquilureidoalquilo, monohaloalquilureidoalquilo, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, carboxyalkyl, to coxicarbonilalquilo, aminocarbonyl, amino carboni monoal qui l l to qu i l o, and dialkylaminocarbonylalkyl. From this subgroup of compounds a preferred class of compounds is that group of compounds wherein: R4 is -O-; R5 is methylene, and Rs is -C (O) -.

Of this class of compounds, a preferred subclass of compounds is that group of compounds wherein: R1 is one or more substituents that are independently selected from the group consisting of halo, alkyl, cycloalkyl, cycloalkylaminoalkyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl , (hydroxy) aralkyl, cyanoalkyl, hal or alkylcarbonylaminoalkyl, alkoxyalkyl, aralkoxyalkyl, alkylthioalkyl, hydroxy-1-one-1-one, aminoalkyl, mono-alkyl-amino-chyl, dialkylamino-alkyl. monoarylaminoalkyl, monoaralkylaminoalkyl, azidoalkyl, monoalkylureidoalkyl, (Alkoxycarbonylalkyl) ureidoalkyl, h i d r o x i a l q u i l a m i n or l q u i l or oxyalkyl aryl carboni l oxy to qui l or coxialquil aral carbonyloxyalkyl, alkylcarbonylalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, and heterocyclylalkyl; R2 is one or more substituents that are independently selected from the group consisting of hydrogen and halo; R3 is phenyl optionally substituted by one or more substituents that are independently selected from the group consisting of hydroxy hydrogenhalo, alkyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano aminoalkoxy, cycloalkyl, cycloalkylaminoalkyl aralkyl, hydroxyalkyl, (monoalkylamino) aralkyl alkoxyalkyl, amino, monoalkylamino, dialkylamino monoa r 1 qui 1 ami no, 1 qu i 1 ca rb on i 1 ami nonalkenyl carboni lamino, cycloalkylcarbonylamino arylcarbonylamino, heterocarbonylamino haloalkylcarbonylamino, alkoxyalkylcarbonylaminoalkoxycarbonylalkylcarbonylamino, (alkylcarbonyl) (alkyl) amino, alkylsulfonyl amino, monoalkylaminoalkyl aminoalkyl, dialkylaminoalkyl monoarylaminoalkyl, monoaralkyl aminoalkyl alkylcarbonylaminoalkyl, arylcarbonylaminoalkyl (alkylcarbonyl) (alkyl) aminoalkyl (cycloalkyalkyl) aminoalkyl alkoxycarbonylaminoalkyl alkoxycarbonylalkylcarbonylaminoalkyl (alkoxycarbonyl) (alkyl) aminoalkyl alkylsulfonylaminoalkyl (alkylsulfonyl) (alkyl) aminoalkyl arylsulphonylaminoalkyl (alkylsulfonyl) (alkyl) aminoalkyl or heterocyclylaminoalkyl, carboxy, alkoxycarbonyl alkylcarbonyl, (hydroxyalkoxy) carbonyl aminocarbonyl, monoalkyl amino carbonyl omonoarylaminocarbonyl (aminocarbonylalkyl) aminocarbonyl (aminoalkyl) aminocarbonyl (hydroxyalkyl) aminocarbonyl dialkylaminocarbonylalkyl, hydroxyamidino, ureido monoalkylureido, monoarylureido, monoaralkylureido (monoalkyl) (monoaryl) ureido (hal or alkylcarbonyl) ureido, ureidoalkyl monoalkylureidoalkyl, dialqui lureidoalkyl monoalkylureidoalkyl, monoaralkylureidoalkyl m o n o h a l o a l q u i l i l a l i l u o l (hal oal qui l) (al qui l) ure i do al qui l o (alkoxycarbonylalkyl) ureidoalkyl, glycinamide monoalkyl glycinamide, amino carbonyl glycinamide (alkoxycarbonylcoxylated) aminocarbonyl (alkoxycarbonyl) alkyl (alkylammonium) glycoamido (alkoxycarbonylalguylcarbonyl) (alkyl) glycinamide (alkoxycarbonylaminoalkylcarbonyl) glycinamide, arylcarbonylglycinate (arylcarbonyl) ( (a) monoalkylaminocarbonyl glycinamide (monoaralkylaminocarbonyl) (alkyl) glycineamido (monoarylaminocarbonyl) glycolamino (monoarylaminocarbonyl) (alkyl) glycinamide alaninamide, heterocyclyl and heterocycloalkyl.

Preferred compounds within this subclass of compounds are selected from the group consisting of the following compounds: (2 S) -1- (4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-f-luorobenzyl) piperazine; 1- (phenoxy) methyl) carbonyl-2-ethyl-4- (4-f luorobenzyl) piperazine, 4- (4-fluorobenzyl) -1- (4-chlorophenoxy) methyl) carbonyl-2-ylpiperazine, 4- (4-fluorobenzyl) -1- (4-chlorophenoxy) methyl) carbonyl-2- (methoxymethyl) piperazine; 4- (4-fluorobenzyl) -1- (4-chlorophenoxy) methyl) carbonyl-2- (acetylamino) methyl) iperazine; 1- (4-chloro-enoxy) methyl) carbonyl-2- (2- (4-f luorobenzyl) amino) ethyl) -4- (4-f luorobenzyl) piperazine; 1- (4-chloro-enoxy) methyl) carbonyl -2- (2- (methyl) amino) ethyl) -4- (4-f luorobenzyl) piperazine; 1- (4-chloro-enoxy) methyl) carbonyl-2- (2- (2-hydroxyethyl) amino) ethyl) -4- (4-f luorobenzyl) piperazine; 4- (4-f-luorobenzyl) -1- (4-chloro-enoxy) -methyl) -carbonyl-3- ((4-chloro-enoxy) -methyl) -carbonyl) -oxi) -methyl-5-methyl-piperazine; 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) met yl) carbonyl-3 - (methoxy) methyl) piperazine; 4- (4-fluorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl -3 - (2 - (methoxy) ethyl) piperazine; 4- (4-f luorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl-3- (2-hydroxy-2- (4-methylphenyl) -ethyl) piperazine; 4 - (4-f luorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl-3- (2-hydroxypropyl) piperazine; 4- (4-fluorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl-3 - (2-hydroxybut-4-ynyl) piperazine; 4- (4-f luorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl-5- (2-hydroxy-2-methylpropyl) piperazine; 4- (4-fluorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl-3- (2-hydroxyethyl) piperazine; 1- (4-chloro-enoxy) methyl) carbonyl-3- (2- (2-hydroxyethyl) amino) ethyl) -4- (4-f luorobenzyl) piperazine; (cis) -4- (4-f luorobenzyl) -1- (4-chlorofenoxyl) methyl) carbonyl -2,3-dimethylpiperazine; (2S, 5R) -1- (4-chloro-3,5-dimethoxyphenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (2S, 5S) -4- (4-f luorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl -2,5-dimethylpiperazine; (2R, 5S) -4- (4-f luorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl-2-methyl-5- (2-methylthio) ethylpiperazine, - (2R, 5R) -4- ( 4-f luorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl-2-methyl-5- (benzyloxy) methyl-piperazine; (2R, 5R) -1- (4-chlorophenoxy) methyl) carbonyl-2-methyl-4 - (4-f-luorobenzyl) -5- ((2-hydroxyethyl) thio) methyl) piperazine: 4- (4-fluorobenzyl) ) -1- (4-chlorophenoxy) methyl) carbonyl-2 - (N- (ethoxycarbonylmethyl) ureido) methyl) piperazine, - (2R, 5S) -1- (4-chlorophenoxy) methyl) carbonyl-2-methyl-5 - (amino) carbonyloxy) methyl -4- (4-f luorobenzyl) piperazine; 4- (4-fluorobenzyl) -1- (4-chlorophenoxy) methyl) carbonyl-3- (acetyl) methyl) piperazine; (2 ~ R, 5R) -4- (4-fluorobenzyl) -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, 5S) -1- (4-chlorophenoxy) methyl) carbonyl-2-methyl-4 - (4-f-luorobenzyl) -5- (diethylamino) methyl) piperazine; (2R, 5S) -1- (4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-f-luorobenzyl) -5- (dimethylamino) methyl) piperazine; (2.5 S) -1- (4-chlorophenoxy) methyl) carbonyl-2-methyl-4 - (4-f-luorobenzyl) -5- ((cyclopropyl) amino) methyl) piperazine; (2R, 5S) -1- (4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-f luorobenzyl) -5- (morpholin-4-yl) methyl) piperazine; (2R, 5R) -1- (4-chlorophenoxy) methyl) carbonyl -2-methyl-4 - (4-f-luorobenzyl) -5- (piperazin-1-yl) methyl) piperazine; (cis) -1- (3,4,5-trimethoxyphenoxy) methyl) carbonyl-2,6-dimethyl-4- (4-f luorobenzyl) piperazine; (cis) -4- (4-f luorobenzyl) -1- (4-chloro-enoxy) ethyl) carbonyl -2,6-dimethylpiperazine, -1- (phenoxy) methyl) carbonyl-2-methyl-4- (4- f luorobenzyl) iperazine, 1- (2 - (acetylamino) phenoxy) methyl) carbonyl-2-methyl-4 - (4-f luorobenzyl) iperazine; 1- (4-chlorophenoxy) methyl) carbonyl-2- (2-hydroxybutyl) propyl (4-fluorobenzyl) piperazine; 1- (4-chloro-enoxy) methyl) carbonyl -2- (2-hydroxybut-3) -enyl) -4- (4-f luorobenzyl) piperazine; 1 (4-chlorophenoxy) -me il) carbonyl-3-trifluoromethyl-4- (4-f-luorobenzyl) piperazine; and (trans) -1- (4-chloro-2- (4- (2,5-di (trifluoromethyl) f enylcarbonyl) -piperazin-1-yl) methyl) phenoxy) methyl) carbonyl -2,5-dimethyl -4- (4-f luorobenzyl) piperazine. Of this subclass of compounds, a preferred group of compounds is that group of compounds wherein: Rla is one or more substituents that are independently selected from the group consisting of alkyl, cycloalkyl, hydroxyalkyl, hydroxyalkenyl, cyanoalkyl, alkoxyalkyl, monoalkylaminoalkyl, azidoalkyl , monoalkylureidoalkyl, aryloxyalkylcarbonyloxyalkyl, and heterocyclylalkyl; R2 is one or more substituents that are independently selected from the group consisting of hydrogen, chloro or fluoro; R3 is phenyl substituted by one or more substituents which are independently selected from the group consisting of hydroxy, halo, alkyl, alkoxy, formyl, nitro cyano, aminoalkoxy, cycloalkylaminoalkyl hydroxyalkyl, (monoalkylamino) aralkyl alkoxyalkyl, amino, monoalkylamino, dialkylamino mono ar 1 qui 1 mi no, al qui 1 ca rb on i 1 ami no alkenyl carboni lamino, cycloalkylcarbonylamino aryl carbon onylamino, heterocyclylcarbonylamino haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, alkylsulfonyl aminoalkyl, moxa 1 qui 1 am inoa 1 qu i 1 or dialkylaminoalkyl, monoaralkylaminoalkyl alkylcarbonylaminoalkyl, arylcarbonylaminoalkyl (alkylcarbonyl) (alkyl) aminoalkyl (cycloalkyl qu) aminoalkyl alkoxycarbonylalkylcarbonylaminoalkyl alkylsulfonylaminoalkyl (alkyl su onyl) (alkyl) aminoalkyl arylsulfonylamine or a l q u i l (arylsul fonyl) (alkyl) aminoalkyl, carboxy to coxi carbonyl, to which carbonyl (hydroxyalkoxy) carbonyl, aminocarbonyl monoalkylaminocarbonyl, monoarylaminocarbonyl (Aminocarbonyl) aminocarbonyl (aminoalkyl) aminocarbonyl (hydroxyalkyl) aminocarbonyl, hydroxyamidino, ureido monoalquilureido, monoarilureido, monoaralquilureido (mo ñ OC) (monoaryl) ureido (hal carbonyl OC) ureido, monoalquilureidoalquilo ureidoalkyl, monoarilureidoalquilo dialquilureidoalquilo, monoaralquilureidoalquilo lquilo monohaloalquilureidoa (hal oalqui l ) (alkyl) ureidoalkyl (alkoxycarbonylalkyl) ureidoalkyl, glycinamide monoalkylglycinamido, aminocarbonyl glycinamide (to the oxy to the qui lca rb on il) gl ici nami do (amino carboni) (al qui l) gl icamido (alkoxycarbonylalkylcarbonyl) (alkyl) glycinamide (to the coxi carbonyl aminoalkyl carbonyl) glycinamide arylcarbonyl 'glycinamide (a carbonyl) (to the which) ammonium glycolate (monoaralkylaminocarbonyl) (alkyl) glycinamide (monoaryl aminocarbonyl) gly icamido (monoarylaminocarbonyl) (alkyl) glycinamide alaninamide, heterocyclyl and heterocyclylalkyl.

Preferred compounds within this group of compounds in this subclass of the group of compounds are selected from the group consisting of the following compounds: 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-2-methyl (4-f luorobenzyl) iperazine; 1- ((4-chlorophenoxy) methyl) carbonyl -2-methyl-4 - (4-f-luorobenzyl) piperazine; 4- (4-Fluorobenzyl) -1- (4-chlorophenoxy) methyl) carbonyl-2-ethylpiperazine, - (2R) -4- (4-f luorobenzyl) -1- (4-chlorofenoxi) methyl) carbonyl-2-propylpiperazine, - (2S) -4- (4-f luorobenzyl) -1- (4 - chlorofenoxi) methyl) carbonyl-2-propylpiperaz ina, 4- ((4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl) -spiro [cyclopropane-1, 2'-piperazine], - ((4-chlorophenoxy) methyl) carbonyl-2-hydroxymethyl-4- (4-f luorobenzyl) piperaz ina, - 4- (4-f luorobenzyl) -1- (4-chlorofenoxi) and il) carbonyl -2 - (2 - (methoxy) ethyl) piperazine; 1- (4-chloro-enoxy) methyl) carbonyl-2- (2- (2-methylpropyl) amino) ethyl) -4- (4-f luorobenzyl) piperazine; 1- (4-chloro-enoxy) methyl) carbonyl-3-methyl-4- (4-f-luorobenzyl) piperazine; 1- (4-chlorophenoxy) methyl) carbonyl-4- (4-fluorobenzyl) -5-methylpiperazine; (2R) -1- (4-chlorophenoxy) methyl) carbonyl-3-methyl-4- (4-f-luorobenzyl) piperazine; (2S) -1- (4-chlorophenoxy) methyl) carbonyl-3-methyl-4- (4-f-luorobenzyl) 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-f luorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl-2,3-dimethylpiperazine; (cis) -1- (4-chloro-oxo) -me il) -car onyl -3,5-dime-il-4 - (4-f-luorobenzyl) -perazine; 4- (4-f luorobenzyl) -1- (4-chlorofenoxi) methyl) carbonyl -2 - (2 - ((4-chloro-enoxy) -methyl) carbonyl) oxy) ethyl-5-methylpiperazine, (2R, 5R ) -1- (4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-f luorobenzyl) -5- (hydroxy) methyl) piperazine; (2R, 5R) - (4-f luorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl-2-methyl-5- (methoxy) -methyl) -perazine; (2R, 5S) -4- (4-f luorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl-2-methyl-5- (1-methylethyl) piperazine; (2R, 5R) - (4-f luorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl-2-methyl-5- (1-hydroxyethyl) piperazine; (2R, 5R) -4- (4-f luorobenzyl) -1- (4-chlorofenoxy) methyl) carbonyl -2-methyl-5- (1-hydroxyprop-3-enyl) piperazine; (2R, 5S) -1- (4-chlorophenoxy) methyl) c-rbonyl-2-methyl-4- (4-f-luorobenzyl) -5- (cyano) methyl) piperazine; (2R, 5R) -1- (4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-f-luorobenzyl) -5- (1, 2,4-triazol-2-yl) methyl) iperazine; (2R, 5R) -1- (4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-f-luorobenzyl) -5- (tetrazolyl) methyl) piperazine; (3S, 5S) -4- (4-f luorobenzyl) -1- (4-chloro-enoxy) 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) iperazine; (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-aminofenoxi) me-il) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; l- (4-Chloro-3-nitrophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (4-chloro-2- (benzylamino) phenoxy) methyl) carbonyl -2,5-dimethyl-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) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (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 1 - (4-nitrophenyl) ureido) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (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) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (4-Chloro-2- (cyclopropylmethyl) aminomethyl) phenoxy) ethyl) -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) aminoethyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine: (trans) - 1- (4-chloro-2- (1-acetyl) (methyl) aminoethyl) phenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- (4-chloro-2- (1- (N-methyl-N'-ethylureido) -ethyl) f-enoxy) methyl) -carbonyl-2,5-dimethyl-4 - (4-f-luorobenzyl) ) piperazine; (trans) -1- (4-chloro-2- (1- (methyl) (ethyl) amino) ethyl) phenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- (4-chloro-2- (1- (dimethylamino) ethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (2R) -1- (4-Chloro-2- (4-t-butoxycarbonylpiperazin-1-yl) methyl) f-enoxy) methyl) carbonyl-2-methyl-4 - (4-f luorobenzyl) piperaz ina, - (trans ) -1- (4-chloro-2- (piperazin-l-yl) methyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (t r a n s) - 1 - (4-c l or r o-2 - (or x a z or l-2-yl inome t yl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; 1- (4-chloro-2- (morpholin-4-ylmethyl) phenoxy) methyl) carbonyl -2-methyl-4- (4-f luorobenzyl) piperazine; (trans) -1- (4-bromo-2-formyl phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- (4-f luoro-3-chlorofenoxi) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; 1- (4-chloro-2-methoxycarbonylphenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) iperazine; (trans) -1- (4-Chloro-2-methoxycarbonylphenoxy) methyl) carbonyl-2,5-dimethyl- (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) -1- (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, - (trans) -1- (3-formylphenoxy) methyl) carbonyl- 2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (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) and yl) 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) iperazine; (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) me il) carbonyl -2,5-dimethyl-4 - (4-fluorobenzyl) piperazine; (trans) -1- (4-methoxy-2-acetylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (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) iperazine; (trans) -1- (2- (2-hydroxyethoxy) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2-Acetyl-4,5-dimethyl-enoxy) -ethyl) -carbonyl-2,5-dimethyl-4- (4-f-luorobenzyl) -piperazine; (trans) -1- (5-methoxy-2- (methoxycarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; 4- (4-fluorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl -2 - (N '-methylureido) -amino) methyl) piperazine, (trans) -1- (4-methyl-2-f ormilf enoxi) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- (3-chloro-5-methoxy phenoxy) methyl) -2,5-dimethyl-4- (4-f luorobenzyl) piperazine, - (trans) -1- (2-methoxy- 5-nor rofenoxi) me il) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazin; (trans) -1- (2- (hydroxymethyl) phenoxy) ethyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazin, - (trans) -1- (2-methylfenoxy) methyl ) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; 1- (4-chlorophenoxy) methyl) carbonyl-2- (2-azidoethyl) -4- (4-chlorobenzyl) piperazine, - (trans) -1- ((4-chloro-2- (f-imido) phenoxy) methyl) carboni 1-2-, 5-dimethyl-4 - (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (maleimido) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((4- (benzylcarbonyl) piperazin-1 i) eti 1) phenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-f) luorobenzyl) iperazine; (trans) -1- ((4-chloro-2- ((4- ((2,3,4-trifluorophenyl) aminocarbonyl) -piperazin-1-yl) methyl) phenoxy) ethyl) carbonyl -2,5-dimethyl -4- (4-fluorobenzyl) iperazine; (trans) - 1 - ((4-chloro-2 - ((4 - ((2-f-luoofenyl) aminocarbonyl) piperazin-1-yl) ethyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- ( 4-Fluorobenzyl) iperazine; (trans) - 1 - ((4-chloro-2 - (N '- ((2,6-difluorophenyl) ureido) phenoxy) methyl) -carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (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) iperazine; (trans) -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; ) -1- ((4-chloro-2- (N 1 - (methoxycarbonylmethylcarbonyl) -N '- (me il) glycinamide) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((N1 - (2-methoxycarbonylethyl) carbonyl-N '- (methyl) glycinamide) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4- f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((N '- (3-methylbenzyl) aminocarbonyl-N' - (methyl) glycinamide) phenoxy) methyl) carbonyl-2,5-dimethyl -4- (4-f luorobenzyl) piperazine, - (trans) -1- ((4-chloro-2- (N- (3-trif luoromethyl-4-f luorofenyl) carbonyl-N '- (methyl) glycinamide ) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((N '- (4-methylbenzyl) aminocarbonyl-N '- (methyl) glycinamide) phenoxy) methyl) carbonyl -2,5 -dimethyl-4 - (4-chlorobenzyl) iperazine; (trans) -1- ((4-chloro-2- ((N1 - (3- chlorophenyl) carbonyl-N- (methyl) glycinamide) phenoxy) methyl) carbonyl -2,5-dimethyl -4- (4-chlorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((N '- (4-f luorobenzyl) aminocarbonyl-N' - (methyl) glycinamide) phenoxy) methyl) carbonyl -2,5-dimethyl-4 - (4 -f luorobenzyl) piperazine; trans) -1- ((4-chloro-2- (N '- (2-yodofenylcarbonyl) glycinamide) -phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- (4-chloro-2- (N '- (2,3-dif luorofenylcarbonyl) glycinamide) -phenoxy) -methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N1 - (4-phenoxy phenyl) aminocarbonyl) -glycinamido) -phenoxy) -methyl) carbonyl-2,5-dimethyl-4 - (4-f-luorobenzyl) piperazine; (trans) -1- (4-chloro-2- (N * - (2,4-difluorylcarbonyl) glycinamide) -phenoxy) methyl) -carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- (4-chloro-2- (2-iodobennylcarbonyl) aminomethyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((ethoxycarbonylmethylcarbonyl) aminomethyl) -phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N '- (3-chloropropyl) ureido ethyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N 1 - (2-fluoro-6-trifluoromethylphenyl) -ureidomethyl) phenoxy) -methyl) carbonyl-2, 5-dimethyl-4- (4-f) luorobenzyl) iperazine, (trans) -1- ((4-chloro-2- ((3-f luorofenyl) carbonylaminomethyl) phenoxy) -methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine , - (trans) -1- ((4-chloro-2- (N '- (2- (ethoxycarbonyl) ethyl) ureidomethyl) -phenoxy) -methyl) carbonyl-2, 5-dimethyl-4- (4-f) luorobenzyl) piperazine; (2S) -1- ((4-chloro-2- (ureido) phenoxy) ethyl) carbonyl-2-methyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (2,5-di (trifluoromethyl) phenyl) carbonyl-aminomethyl) -phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f-luorobenzyl) ) piperazine; and (trans) -1- ((4-chloro-2- (N1 -2- (phenyl) cyclopropyl) ureidomethyl) -phenoxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine. A more preferred group of these compounds in this subclass of groups of compounds are those compounds in which: R1 is one plus substituents that are independently selected from the group consisting of alkyl and hydroxyalkyl; R2 is one or more substituents that are independently selected from the group consisting of hydrogen, chloro or fluoro; R3 is phenyl substituted by one or more substituents independently selected from the group consisting of halo, alkyl, alkoxy, formyl, nitro, cycloalkylaminoalkyl, hydroxyalkyl, amino, alkylcarbonylamino, hal or alkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, alkylsulphonylamino , aminoalkyl, monoalkylaminoalkyl or, dialkylaminoalkyl, (alkylsulfonyl) (alkyl) aminoalkyl, alkylcarbonyl, aminocarbonyl or, monoalkylaminocarbonyl, monoarylaminocarbonyl or, (aminocarbonylalkyl) aminocarbonyl, (aminoalkyl) aminocarbonyl, hydroxyamidino, ureido, (haloalkylcarbonyl) ureido, ureidoalkyl, glycinamide, monoalkylglycinamido, aminocarbonylglycine gone, (a l c i i i i i i i i i c i i i i i i i i i i i i (amino c arboni l) (alky l) gl i c imamido, (to coxy carbonyl aminoalkyl carbonyl) glycinamide, alaninamide, and heterocyclylalkyl.

Preferred compounds within this most preferred group of compounds in this subclass of groups of compounds are 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) ethyl) 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, 5S) -1 - ((4-chloro-2- (aminocarbonyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- ((4-fluorobenzyl) iperazine; (2S, 5R) -1- ((4-bromo-3, 5-dimethoxyphenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (2R, 5S) -1- ((3-hydroxy-5-methylphenoxy) methyl) carbonyl-2,5-dimethyl -4- (4-fluorobenzyl) iperazine; (2S, 5R) -1- ((4-nitro-3-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (2R) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl l-4- (4-fluorobenzyl) piperazine, - 4 - ((4-fluorobenzyl) -1- (4-chlorophenoxy) methyl) carbonyl -2 - (2-hydroxyethyl) iperazine; (trans) -4- ((4-fluorobenzyl) -1- (4-chlorophenoxy) methyl) carbonyl-2,5-dimethylpiperazine; (2R, 5S) -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, 5S) -l - ((4-chloro-3,5-dimethoxyphenoxy) methyl) carbonyl-2, 5-dimethyl -4- ((4-fluorobenzyl) iperazine; (2R, 5S) -4- ((4-fluorobenzyl) -1- (4-chlorophenoxy) methyl) carbonyl-2- (2-hydroxyethyl) -5-methylpiperazine; 2R, 6R) -4- ((4-fluorobenzyl) -1- (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, - ( 2R, 5S) -l- ((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-fluorobenzylperazine; (trans) -1- ((4-chloro-2 - (aminome il) phenoxy) methyl) carbonil -2, 5-dimethyl-4- (4-fluorobenzyl) iperazine; (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) ethyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine, - (trans) -4- (4-f luorobenzyl) -1- (( 2-acetylamino-4-chlorophenoxy) methyl) carbonyl-2, 5-dimethylpiperazine, - (trans) -1- ((4-chloro-2- (propylcarbonylamino) phenoxy) ethyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (methoxymethylcarbonylamino) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (t r a n s) - 1 - ((4-c l or r o - 2 - (2 - (methoxycarbonyl) ethylcarbonylamino) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (2- (ethoxycarbonyl) ethylcarbonylamino) -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) iperazine; (trans) -1- ((4-chloro-2- (bromomethylcarbonylamino) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (2R) -1- ((4-chloro-2- (glycinamide) phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((N1-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) glycinamide) phenoxy ) -methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (aminocarbonyl) (me il) glycinamide) -phenoxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N1-ethylurio) 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 hydrochloride 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) iperazine; (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 ) methyl) phenoxy) methyl) 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-methy1-piperazyl-l-yl) methyl) phenoxy) ethyl) -carbonyl-2, 5-dimethyl-4- (4-f-luorobenzyl) piperazine; (t ran s) - 1 - ((4 - chloro - 2 - ((p ip e ra z in - 1 - i 1) eti 1) 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) 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; (2 R, 5 S) - 1 - ((4-chloro-2 - ((p ip e ra z in-1-yl) methyl) phenoxy) methyl) carbonyl-2, 5 -dimethyl-4- (4 -f luorobenzyl) piperazine; (trans) -1- ((4-Chloro- (4-γ-ut oxy-arb oni lp ipe r az in-1-yl) methyl) phenoxy) methyl) carbonyl-2, 5-dimethyl (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (imidazol-1-ylmethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((-chloro-2 - (1- (imidazol-1-yl) ethyl) phenoxy) ethyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((4-chloro-2- (triazol-1-ylmethyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((4-chloro-2- (tetrazol-1-ylmethyl) f enoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((morpholin-4-yl) methyl) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (2R) -1- ((4-chloro-2-aminocarbonylphenoxy) methyl) carbonyl-2-methyl-4- (4-f luorobenzyl) piperazin; l - ((4-chloro-2-f ormilf enoxy) ethyl) carbonyl-2-methyl-4 - (4-fluorobenzyl) piperazine; (2R, 5S) -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) iperazine; (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) piperazine; (trans) -1- ((4-chloro-2- ((2-aminoethyl) aminocarbonyl) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fiuorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((4-aminocarbonylphenyl) aminocarbonyl) -phenoxy) ethyl) 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-flucrobenzyl) piperazine; (trans) -1- ((2- (aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((N 1 - (trichloromethyl carbonyl) ureido) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) 1- ((4-chloro-2 - (N '- (meth oxime-t-carbonyl) -glycinamido) -phenoxy) methyl) -carbonyl-2, 5, dimethyl-4- (4-f luorobenzyl) piperazine; ) -1- ((4-chloro-2- (N 1 - (ethoxycarbonylaminocarbonyl) -glycinamido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine The most preferred group of compounds within this subclass of group of compounds are those compounds wherein R2 is 4-fluoro and R3 is phenyl substituted at the 4-position with chlorine and at the 2-position by aminocarbonyl, ureido or glycinamide: specifically, the compounds are selected from the group consisting of of the following compounds: (2R, 5S) -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-fluorob) encil) piperazine; (2R) -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; (2R, 5S) -1 - ((4-chloro-2- (ureido) phenoxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; and (2R, 5S) -1- ((4-chloro-2- (glycinamide) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine. Of the subgroup of compounds set forth above, another preferred class of compounds are those compounds wherein: R 4 is -N (R 7) -; R5 is methylene; Rs is -C (O) -, - and R7 is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkyl carbonyl, alkylcarbonylalkyl, aralkyl or carbonyl, aralkylcarbonylalkyl, aminecarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl. Of this class of compounds, a preferred subclass of compounds are those compounds wherein: Rla is one or more substituents that are independently selected from the group consisting of halo, alkyl, cycloalkyl, cycloalkylaminoalkyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, ( hydroxy) aralkyl, cyanoalkyl, hal or alkylcarbonylaminoalkyl or, alkoxyalkyl, aralkoxyalkyl, alkyltioalkyl, hydroxyalkylthioalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, monoarylaminoalkyl, monoaralkylaminoalkyl, azidoalkyl, monoalkylureidoalkyl, (The coxicarbonilalquil) ureidoalkyl, h i d r o x i a l q u i l a m i n or l q u i l o, r i l ox i to l qu i l c a rb o n i l o x i to l qu i l o, r a l c ox i to l qu i l c a rb o n i l ox i to l qu i l o, alkylcarbonylalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, and heterocyclylalkyl; R2 is one or more substituents that are independently selected from the group consisting of hydrogen and halo, - R3 is phenyl optionally substituted by one or more substituents that are independently 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, monoaralkylamino, alkylcarbonylamino, alkenyl carbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylamino, hal or alkylcarbonylamino, coxyalkyl carbonylamino, coxycarbonyl, aminoalkyl, (alkylcarbonyl) (alkyl) amino, alkylsulphonylamino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, monoalkylaminoalkyl, monoaralkylaminoalkyl, alkylcarbonylaminoalkyl arylcarbonylaminoalkyl (alkyl) arbonil) (alkyl) aminoalkyl (c i c l o a l q u i to l q u i l) to m i n or l q u i l o a l c or x i c a r b o n i l a m i n or l q u i l or alcoxicarbonilalquilcarbonilaminoalquilo (alkoxycarbonyl) (alkyl) aminoalkyl a l q u i l s u l f o n i l a m i n or l q u i l or (onil alquilsulf) (alkyl) aminoalkyl r i l s u l f o n i l a m i n or l q u i l o (aryl sulphonyl) (to which) aminoalkyl or heterocyclylaminoalkyl, carboxy, alkoxycarbonyl alkylcarbonyl, (hydroxyalkoxy) carbonyl aminocarbonyl or, monoalkylaminocarbonyl or m o n a r i l a m i n o c a r b o n (Aminocarbonyl) aminocarbonyl (a m i n or l q u i l) to m i n or c a r b o n i l or (h i d r o x i a l q u i l) to m i n or c a r b o n i l or dialkylaminocarbonylalkyl, hydroxyamidino, ureido monoalquilureido, monoarilureido, monoaralquilureido (monoalkyl) (monoaryl) ureido (hal or alkylcarbonyl) ureido, ureidoalkyl monoalkylureidoalkyl, dialkylureidoalkyl monoarylureidoalkyl, monoaralkylureidoalkyl monohaloalkylureidoalkyl (halalkyl) (alkylamide), (alkoxycarbonylalkyl) ureidoalkyl, glycinamide, monoalkyl glycinamide , aminocarbonylglycinamido, (al coxi ali ca rb on il) gl ic inami do, (amino c arboni l) (alkyl) gl i cinnamide, (Alcoxicarbonilalquilcarbonil) glycinamido (alkyl), (the coxi carbonyl carbonyl aminoalkyl) glycinamido, r i l c a r b o n i l g l i c i n a m i d or (ari l carboni l) (a l qu i l) gl i c i nami do, (monoaralquilaminocarbonil) glycinamido, (monoaralkylaminocarbonyl) (alkyl) glycinamide, (monoaryl aminocarbonyl) gl i camido, (monoarylaminocarbonyl) (alkyl) glycinamide, alaninamide, heterocyclyl and heterocyclylalkyl. A preferred group of compounds in this subclass of group of compounds is that group wherein: Rla is one or more substituents that are independently selected from the group consisting of alkyl, cycloalkyl, hydroxyalkyl, hydroxyalkenyl, cyanoalkyl, alkoxyalkyl, monoalkylaminoalkyl, azidoalkyl, monoalkylureidoalkyl, aryloxyalkylcarbonyloxyalkyl, and heterocyclylalkyl; R2 is one or more substituents that are independently selected from the group consisting of hydrogen, chloro or fluoro; yl substituted by one or more substituents independently selected from the group consisting of hydroxy, halo, alkyl, alkoxy, formyl, cyano nitro, alkylamino, hydroxyalkyl cycloalkylaminoalkyl, (monoalkylamino) aralkyl alkoxyalkyl, amino, monoalkylamino, monoaralquilamino dialkylamino, alkenyl alkylcarbonylamino carboni lamino, cycloalkylcarbonylamino aryl carbonylamino, have erociclilcarbonilamino haloalkylcarbonylamino, alkoxyalkylcarbonylamino alcoxicarbonilalquilcarbonilamino, onilamino alquilsulf aminoalkyl, monoalkylaminoalkyl dialkylaminoalkyl, aminoalkyl or monoaralkyl alkylcarbonylaminoalkyl, arylcarbonylaminoalkyl (alkylcarbonyl) (alkyl) minoalquilo (C i c l o a l q u i to l qu i l) to m i n or l q u i l or alcoxicarbonilalquilcarbonilaminoalquilo a l q u i l s u.l f o n i l a m i n or l q u i l or (onil alquilsulf) (alkyl) aminoalkyl r i l s u l f o n i l a m i n or l q u i l o (arylsulf onyl) (alkyl) aminoalkyl, carboxy to coxi carbonyl, to which carbonyl (hydroxyalkoxy) carbonyl, aminocarbonyl 1 or monoalkylaminocarbonyl, monoarylaminocarbonyl (aminocarbonylalkyl) aminocarbonyl (aminoalkyl) aminocarbonyl (hydroxyalkyl) aminocarbonyl, hydroxyamidino, ureido monoalkylureido, monoarylureido, monoalkylureido (monoalkyl) (monoaryl) ureido (haloalkylcarbonyl) ureido, ureidoalkyl monoalkylureidoalkyl, dialkylureidoalkyl monoalkylureidoalkyl, monoaralkylureidoalkyl monohaloalkylureidoalkyl (halalkyl) (alkylated) to alkyl (alkoxycarbonylalkyl) ureidoalkyl, glycinamide monoalkyl glycinamide, amino carbonyl glycinamide (The coxial gui lc arb on yl) gl ici nami do (amino c Arboni l) (alk l) gl ic inamido (alcoxicarrbonilalquilcarbonil) (alkyl) glycinamido (the coxicarbonilaminoalquilcarbonil) glycinamido arilcarbonilglicinami do (ari l carboni l) (to qu yl ) gl icamy (monoaralkylaminocarbonyl) (alkyl) glycinamide (monoalkyl aminocarbonyl) gly icamide (monoarylaminocarbonyl) (alky1) gly icamidoamine, heterocyclyl and heterocyclylalkyl. A more preferred group in this subclass of group of compounds are those compounds in which: R1 is one plus substituents that are independently selected from the group consisting of alkyl and hydroxyalkyl; R2 is one or more substituents that are independently selected from the group consisting of hydrogen, chloro or fluoro; R 3 is phenyl substituted by one or more substituents which are independently selected from the group consisting of halo, alkyl, alkoxy, formyl, nitro, cycloalkylaminoalkyl, hydroxyalkyl, amino, alkylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, alkylsulfonylamino, aminoalkyl, monoalkylaminoalkyl , dialkylaminoalkyl, (alkylsulfonyl) (alkyl) aminoalkyl, alkylcarbonyl, aminocarbonyl, monoalkylaminocarbonyl or, m o n o a r i l a m a n a c a r b o n i l, (aminocarbonylalkyl) aminocarbonyl, (aminoalkyl) aminocarbonyl, hydroxyamidino, ureido, (haloalkylcarbonyl) ureido, ureidoalkyl, glycinamide, monoalkylglycinamido, aminocarbonylglycine gone, (to coxi al qu i l c arb on i l) gl i-c inami do, (aminocarbonyl) (alkyl) gl i c imamido, (alco-carbonylaminoalkylcarbonyl) glycinamide, alaninamide, and heterocyclylalkyl. An even more preferred group of compounds in this subclass of group of compounds are those 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 with aminocarbonyl, ureido or glycinamide. The preferred compounds in this group are selected from the group consisting of the following compounds: (trans) -1- ((4-chlorophenylamino) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) iperazine 1- ((4-chloro-2- (aminocarbonyl) phenylamino) methyl) carbonyl-2-methyl-4- (4-f luorobenzyl) piperazine; and 1- ((4-chlorophenylamino) methyl) carbonyl-2-methyl-4- (4-f-luorobenzyl) piperazine. Of the subgroup of compounds that is stamped above, another class of preferred compounds are those compounds wherein: R 4 is -C (R 8) 2 -, - Rs is methylene; Rs is -C (0) -; and each R 8 is independently selected from the group consisting of hydrogen, alkyl, amino, monoalkylamino, dialkylamino, alkylcarbonylamino, cycloalkylcarbonylamino, cycloalkylalkylcarbonylamino, alkoxycarbonylamino, at 1 to 1 amino, 1 to 1 arbonylamino, at oxycarbonyl to the alkylcarbonyl amino, alkylcarbonylaminoalkyl, cycloalkylcarbonyl aminoalkyl, alkoxycarbonylaminoalkyl, heterocycliccarbonylaminoalkyl, arylsulphonylamino, alkylsulphonylaminoalkyl, ureido, monoalkylureido, monohaloalkylureido, ureidoalkyl, monoalkylureidoalkyl, monohaloalkylureidoalkyl, aminoalkyl, monoalkylaminoalkyl, and dialkylaminoalkyl. A preferred subclass of compounds of this class of compounds are those compounds in which: Rla is one or more substituents that are independently selected from the group consisting of halo, alkyl, cycloalkyl, cycloalkylaminoalkyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy) ) aralkyl, cyanoalkyl, haloalkylcarbonylaminoalkyl or, alkoxyalkyl, aralkoxyalkyl, alkylalkyalkyl, hydroxyalkylthioalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, monoalkylaminoalkyl, monoaralkylaminoalkyl, azidoalkyl, monoalkylureldoalkyl, (alkoxycarbonylalkyl) ureidoalkyl, hydroxyalkylaminoalkyl, aryl oxalic The cycloalkyl, the aralk oxyal, the cycloalkyl, the alkylcarbonylalkyl, the alkoxycarbonyl, the alkoxycarbonylalkyl, and the heterocyclylalkyl; R2 is one or more substituents that are independently selected from the group consisting of hydrogen and halo; R3 is phenyl optionally substituted by one or more substituents that are independently 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, monoaralkylamino, alkylcarbonylamino, alkenyl carboni lamino, cycloalkylcarbonylamino, aryl carbonylamino, hexylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, coxycarbonyl, cycloalkyl ammonium, (Alkylcarbonyl) (alkyl) amino, onlamino alquilsulf, aminoalquilaminoalquilamino, dialkylaminoalkyl, monoarilaminoalquilo, monoaralquilaminoalquilo, alkylcarbonylaminoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl) (alkyl) aminoalkyl, (c i c l o a l q u i to l qu i l) to m i n or l q u i l o a l c or x i c a r b o n i l a m i n or l q u i l or alcoxicarbonilalquilcarbonilaminoalquilo (alkoxycarbonyl) (alkyl) aminoalkyl a l q u i l s u l f o n i l a m i n or l q u i l o (alkyl sulfonyl) (alkyl) aminoalkyl arylsulfonylaminoalkyl (aryl sulphonyl) (alkyl) aminoalkyl or heterocyclylaminoalkyl, carboxy, alkoxycarbonyl alkylcarbonyl, (hydroxyalkoxy) carbonyl amino carbonyl, monoalkylaminocarbonyl, monoalkylaminocarbonyl or (aminocarbonylalkyl) aminocarbonyl (aminoalkyl) aminocarbonyl -O (hydroxyalkyl) aminocarbonyl dialkylaminocarbonylalkyl, hydroxyamidino, ureido monoalkylureido, monoalkylureido, monoaralkylureido (monoalkyl) (monoaryl) ureido (haloalkyl carbonyl) ureido, ureidoalkyl monoalkylureidoalkyl, dialkylureidoalkyl monoarylureidoalkyl, monoaralkylureidoalkyl monohaloalkylureidoalkyl (halalkyl) (al qu il) re ally with allyl (alkoxycarbonylalkyl) ureidoalkyl, glycinamide monoalkylglycinamido, aminocarbonylglycinamido (alkoxyalkyl) lcarbonyl) glycinamide, (aminocarbonyl) (alkyl) glycinamide, (alkoxycarbonylalkylcarbonyl) (alkyl) glycinamide, (to the coxy carbonyl aminoalkylcarbonyl) glycinamide, to r i l c a r b o n i l i n i l i a m i d, (arylcarbonyl) (alkyl) glycinamide, (monoaralkylaminocarbonyl) (alkyl) glycinamide, (monoarylaminocarbonyl) glycinamide, (monoarylaminocarbonyl) (alkyl) glycinamide, alaninamide, heterocyclyl and heterocyclylalkyl. A preferred group of compounds within this subclass of preferred compounds are those compounds wherein: Rla is one or more substituents that are independently selected from the group consisting of alkyl, cycloalkyl, hydroxyalkyl, hydroxyalkenyl, cyanoalkyl, alkoxyalkyl, monoalkylaminoalkyl, azidoalkyl, monoalkylureidoalkyl, aryloxyalkylcarbonyloxyalkyl and heterocyclylalkyl; R2 is one or more substituents that are independently selected from the group consisting of hydrogen, chloro or fluoro; R3 is phenyl substituted by one or more substituents that are independently selected from the group consisting of hydroxy, halo, alkyl, alkoxy, formyl, nitro, cyano, aminoalkoxy, cycloalkylaminoalkyl, hydroxyalkyl, (monoalkylamino) aralkyl, alkoxyalkyl, amino, monoalkylamino, dialkylamino, monoaralkylamino, alkylcarbonylamino alkenyl lamino carboni, cycloalkylcarbonylamino aryl lamino carboni, haloalkylcarbonylamino ylcarbonylamino Parallel Synthesis, alcoxicarbonilalquilcarbonilamino alkoxyalkylcarbonylamino, onilamino alquilsulf aminoalkyl, monoalkylaminoalkyl dialkylaminoalkyl, monoaralkyl aminoalkyl or alkylcarbonylaminoalkyl, arylcarbonylaminoalkyl (alkylcarbonyl) (alkyl) aminoalkyl (ci cl oalqui l to qui l) aminoal qu yl alcoxicarbonilalquilcarbonilaminoalquilo alkylsulfonylaminoalkyl (alkylsulf onyl) (alkyl) aminoalkyl arylsulfonylaminoalkyl (aryl sulf onyl) (alkyl) aminoalkyl , carboxy alkoxycarbonyl, alkylcarbonyl (hydroxyalkoxy) carbonyl, aminocarbonyl monoalkylaminocarbonyl, monoarylaminocarbonyl (aminocarbonylalkyl) aminocarbonyl (a m i n o a l q u i l) a m i n o c a r b o n i l o (hydroxyalkyl) aminocarbonyl, hydroxyamidino, ureido monoalkylureido, monoarylureido, monoaralkylureido (m o n o a l q u i l) (m o n o a r i l) u r e i o, (halkalkylcarbonyl) ureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, m o n or h a l or a q u i l a r i i a l i a l, (hal oal qui l) (al qui l) u re i do a l l i l, (alkoxycarbonylalkyl) ureidoalkyl, glycinamide, monoalkyl glycinamide, amino carbonyl glycinamide, (to coxialqu i l ca rb on i l) gl i c i nami do, (amino carboni l) (alkyl) gl i c inamido, (Alcoxicarbonilalquilcarbonil) glycinamido (alkyl), (the carbonyl coxi aminoalkyl onyl carb) glycinamido, r i l c a r b o n i l g l i c i n a m i d or (a ril carboni l) (a l qu i l) gl i c i nami do, (monoaralquilaminocarbonil) (alkyl) glycinamido, (monoarylaminocarbonyl) gl icinamide, (monoarylaminocarbonyl) (alkyl) glycinamide, alaninamide, heterocyclyl and heterocyclylalkyl. A more preferred group of compounds within this subclass of compounds are compounds wherein: Rla is one or more substituents that are independently selected from the group consisting of alkyl and hydroxyalkyl; R2 is one or more substituents that are independently selected from the group consisting of hydrogen, chloro or fluoro; Re is phenyl substituted by one or more substituents independently selected from the group consisting of halo, alkyl, alkoxy, formyl, nitro, cycloalkylaminoalkyl, hydroxyalkyl, amino, alkylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, the alkyl carbonyl coxi - - carbonylamino, onilamino alquilsulf , aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, (alkylsulfonyl) (alkyl) aminoalkyl, alkylcarbonyl, aminocarbonyl, monoalkylaminocarbonyl, monoarylaminocarbonyl, (aminocarbonylalkyl) -aminocarbonyl, (aminoalkyl) aminocarbonyl, hydroxyamidino, ureido, (haloalkylcarbonyl) ureido, ureidoalkyl, glycinamide, monoalkylglycinamido, aminocarbonylglycinamido, (alkoxyalkylcarbonyl) -glycinamide , (aminocarbonyl) (alkyl) glycinamide, (alkoxycarbonylaminoalkylcarbonyl) glycinamide, alaninamide, and heterocyclylalkyl. An even more preferred group of compounds of this subclass of group of compounds are those compounds wherein: R 2 is 4-fluoro; R3 is phenyl substituted at the 4-position with chlorine and optionally substituted at the 2-position with aminocarbonyl, ureido or glycinamide; and R8 is hydrogen and the other R8 is selected from the group consisting of amino, alkylcarbonylamino, ino cicloalquilcarbonilam, cicloalquilalquilcarbonilamino, alkoxycarbonylamino, onilamino alquilsulf, arylcarbonylamino, the c oxy c Arboni lal qu ILCA rb on amino yl, alquilcarbonilaminoal chyle, cicloal qu ILCA rb onyl am inoal qu yl, alcoxicarbonilaminoal chyle, heterocyclylcarbonylaminoalkyl, onilamino arilsuf, onilaminoalquilo alquilsulf, ureido, monoalquilureido, monohaloalquilureido, ureidoalkyl, monoalquilureidoalquilo, monohaloalquilureidoalquilo, and aminoalkyl. The even more preferred compounds of this group preferred are those compounds selected from the group consisting of the following compounds: (trans) -1- (2 - (4 - enyl clorof) -3 - (onilamino metilsulf) propyl) carbonyl -2, 5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- (2- (4-chloro-enyl) -3- (acetylamino) propyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) 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) ropil) 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- C2- (4-chlorophenyl) -2- ((ethoxycarbonylmethylcarbonylamino) -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) 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-f-luorobenzyl) 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) 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-chlorobenzyl) iperazine; (trans) -1- (2- (4-chlorophenyl) -3- (cyclopentylcarbonylamino) propyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (T r a n s) - 1 -_ (2 - (4 - c l o r o f e n i l) - 3 - (N '- (t -butyl) ureido) propyl) carbonyl-2, 5 -dimethyl -4 - (4 luorobencil -f) piperazine; (trans) -1- (2- (4-chlorophenyl) -3- (N 1 - (ethyl) ureido) propyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1 - (2- (4-chlorophenyl) -3- (N '- (3-chloropropyl) ureido) ropil) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; and (trans) -1- (2- (4-chlorophenyl) -3- ((morpholin-4-yl) carbonylamino) -propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine. Of the compounds of formula (la), another group of preferred compounds are those compounds wherein: R3 is a heterocyclic ring system substituted by one or more substituents that are independently selected from the group consisting of hydrogen, hydroxy, halo, alkyl , alkylsulfonyl, arylsulfonyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano haloalkoxy, alkenyl, alkynyl, aryl, aralkyl amino, monoalkylamino, dialkylamino, monoarylamino monoaralkylamino, alkylcarbonylamino, coxycarbonyl amino, alkenylcarbonylaminocycloalkylcarbonylamino, arylcarbonyllaminohaloalkylcarbonylamino, alkoxyalkylcarbonylamino to c oxy carboni l to qu rb on ILCA yl ami no (alkylcarbonyl) (alkyl) amino (alkoxycarbonyl) (alkyl) amino, onilamino alquilsulf aminoalkyl, monoalkylaminoalkyl dialkylaminoalkyl, alkylcarbonylaminoalkyl yl arilcarbonilaminoalqu (alkylcarbonyl) (alkyl) am inoalquilo alkoxycarbonylaminoalkyl, carboxy, aralkoxycarbonyl alkoxycarbonyl, alkylcarbonyl, arylcarbonyl aralqui l carboni l or aminocarbonyl or monoalkylaminocarbonyl, monoarilaminocarbonilo dialkylaminocarbonyl, aminocarbonylalkyl m or n or l q u i l a m i n or c a r b o n i l l q u i l o d i a l q u i l a m i n or c a r b o n i l l q u i l or monoarilaminocarbonilalquilo, guanidino, ureido monkey l qu i l u r e i d o, u r e i do to l qu i l or monoalquilureidoalquilo, and glycinamido.

Of this group of compounds, a preferred subgroup of compounds is that group of compounds wherein: R4 is -0-, -N (R7) - or -C (R8) -; Rs is an alkylene chain; R7 is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, carbonylalkyl alkyl, aralkyl or carbonyl, aralquilcarbonilalquilo, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl; and each R8 is independently selected from the group consisting of hydrogen, alguilo, aryl, aralkyl, hydroxy, alkoxy, hydroxyalkyl, alkoxyalkyl, amino, monoalkylamino, dialkylamino, alkylcarbonylamino, cycloalkylcarbonylamino, cicloalquilalquilcarbonil- to ino, alcoxicarbonilaraino, alkylsulfonylamino, arylcarbonylamino, alcoxicarbonilalquilcarbonilamino, (alkylcarbonyl). (alkyl) amino, aralkylcarbonylamino, (Aralkylcarbonyl) (alkyl) amino, alkyl carbonylamino- alkyl, ci cl 1 OC carboni aminoalqui 1 or, alkoxycarbonylaminoalkyl, (alkylcarbonyl) (alkyl) - aminoalkyl, aralkyl carbonyl aminoalqui it, heterocyclylcarbonylaminoalkyl, (aralkylcarbonyl) - (alkyl) aminoalkyl, arylsulfonylamino, alkyl-sulfonylaminoalkyl, ureido, monoalkylureido, monohaloalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monohaloalkylureidoalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, and dialkylaminocarbonylalkyl. Of this subset of compounds, a preferred class of compounds are those compounds wherein: R4 is -O-, - R5 is methylene; and R6 is -C (O) -. Of this class of compounds, a preferred subclass of the group of compounds are those compounds wherein: Rla is one or more substituents which are independently selected from the group consisting of halo, alkyl, cycloalkyl, cycloalkylaminoalkyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy) aralkyl, cyanoalkyl, haloalquilcarbonilaminoalquilo, alkoxyalkyl, aral coxialqui so, the qui lt ioal quil or, hydroxyalkylthioalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, • monoarilaminoalquilo, monoaralquilaminoalquilo, azidoalkyl, monoalquilureidoalquilo, (alkoxycarbonylalkyl) ureidoalkyl, Uilo hidroxialquilaminoalq, aryl Oxygen, which is oniloxial, which is aralk oxide, which is an alkyl oxyalkyl, alkylcarbonylalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, and heterocyclylalkyl; and no or more substituents that are independently selected from the group consisting of hydrogen and halo. A group of preferred compounds in this subclass of preferred group of compounds are those compounds wherein R3 is selected from the group consisting of "azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzoxazoyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranil, benzothienyl, carbazolyl, cinnolinyl, decahydroisoquinolyl, dioxolanyl, furyl, isothiazolyl, quinuclidinyl, imidazolyl, imidazolidyl, imidazolidinyl, isothiazolidinyl, indolyl, isoindolyl, indolinyl, isoindolinyl, indanyl, indolizinyl, isoxazolyl, isoxazolidinyl, morpholinyl, naphthyldidinyl, oxadiazolyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxoazepinyl, oxazolyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, phenazinyl, phenothiazinyl, phenoxazinyl, fthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, pyridinyl , pyrazinyl, pyrimidinyl, pyrid zinyl, quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, thiazolyl, thiazolidinyl, thiadiazolyl, triazolyl, tetrazolyl, tetrahydrofuryl, tetrahydropyranyl, thienyl, thiamorpholinyl, thiamorpholinyl sulfoxide, and thiamorpholinyl sulfone. A more preferred group of compounds in this preferred subclass of compounds are those compounds wherein R3 is benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, quinolinyl, indolyl, indolinyl, oxazolyl, imidazolyl, or benzothienyl. A preferred compound of 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 for treating an inflammatory disorder in a human, which method comprises administering to the human in need of such treatment a therapeutically effective amount of a compound of formula (la) as described in the above. A preferred method is the method of treating inflammatory disorders selected from the group consisting of multiple sclerosis, leucoe cefalopatía, encephalomyelitis, Alzheimer's disease, Guillain-Barre syndrome, acute renal transplant rejection cell mediated allograft rejection, arthritis rheumatoid, atherosclerosis, urticaria, angioderma, allergic conjunctivitis, atopic dermatitis, allergic contact dermatitis, drug allergy or insect bites and systemic anaphylaxis. Another aspect of the invention is a method for treating an inflammatory disorder in a human, which method comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (Ib) as described in the Brief Description of the invention. A preferred method is that method which comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (Ib) wherein: R3 is a carbocyclic ring system substituted by one or more substituents independently from the group consisting of hydrogen, hydroxy, onyl hidroxisulf, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, ynyl alquilsulf, alquilsuf selected onyl, arylsulfonyl, alkyl thioalkyl, alkylsulphonylalkyl, alkylsulphonylalkyl, alkoxy, hydroxyalkoxy, aryloxy, haloalkyl, formyl, frylamylalkyl, 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, aralkoxyalkyl, amino, monoalkylamino, dialkylamino, monoarylamino, monoaralkylamino, aminoalkylamino, heterocyclylamino, (Cycloalkylalkyl) amino, alkylcarbonylamino, alkoxycarbonylamino, cycloalkylcarbonylamino alquenilcarbonilamino_, ar i 1 i ca rb on one ami no, ylcarbonylamino Parallel Synthesis, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkyl alkylcarbonylamino, (alkylcarbonyl) (alkyl) amino, (alkoxycarbonyl) (alkyl) amino, onilamino alquilsulf, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, hydroxyalkylaminoalkyl, monoarylamino-alkyl, monoaralquilaminoalquilo, alkylcarbonyl -aminoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl) (alkyl) aitiinoalquilo, (cycloalkyalkyl) aminoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylalkylcarbonylaminoalkyl, (alkoxycarbonyl) (alkyl) -aminoalkyl, alkylsulphonylaminoalkyl, (alkylsulfonyl) (alkyl) aminoalkyl, arylsulfonylaminoalkyl, (arylsulfonyl) (alkyl) aminoalkyl, heterocyclylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, (hydroxyalkoxy) carbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alcoxialquilcarboniloxi-alkyl, dialqui 1 aminocarboni 1 oxyalkyl or, alkylcarbonylalkyl, arylcarbonylalkyl, aralkyl-carbonyl, aminocarbonyl, mono-carbonyl, dialkylaminocarbonyl, monoarilaminocarbonilo, monoaralquilaminocarbonilo, ( aminocarbonylalkyl) aminocarbonyl, (monoalquilaminocarbonilalquil) aminocarbonyl, (carboxyalkyl) aminocarbonyl, (alkoxycarbonylalkyl) aminocarbonyl, (aminoalkyl) aminocarbonyl, (hydroxyalkyl) aminoca rbonyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoalkylaminocarbonylalkylated, monoaralkylaminocarbonylalkyl, amidino, hydroxyamidino, guanidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, monohaloalkylureido, (monoalkyl) (monoaryl) ureido, dialkylureido, diarylureido, (haloalkylcarbonyl) ureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl) - (alkyl) ureidoalkyl, (alkoxycarbonylalkyl) -ureidoalkyl, glycinamide, monoalkylglycinamido, aminocarbonylglycinamido, (alkoxyalkylcarbonyl) -glycinamido, (aminocarbonyl) (alkyl) glycinamide, (alkoxycarbonylalkylcarbonyl) (alkyl) glycinamide, (to coxy carbonyl aminoalkylcarbonyl) glycinamide, arylcarbonylglycinamide, (arylcarbonyl) (alkyl) -glycinamido, (monoaralkylaminocarbonyl) glycinamide, (monoaralkylaminocarbonyl) (alkyl) glycinamide, (monoarylaminocarbonyl) glycinamide, (monoarylaminocarbonyl) (alkyl) glycinamide, glycinamidoalkyl, alaninamide, monoalkylalaninamide, alaninamidoalkyl, heterocyclyl and heterocyclylalkyl. An even more preferred method which comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (Ib) wherein: R4 is -0-, -N (R7) - or -C ( R8) -; R5 is an alkylene chain; R7 is selected from the group consisting of hydrogen, alkyl, aryl or, aralkyl, alkyl carbonyl, 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, cycloalkylcarbonylamino, cicloalquilalquilcarbonil- amino, alkoxycarbonylamino, alkylsulfonylamino, arylcarbonylamino, alcoxicarbonilalquilcarbonilamino, (alkylcarbonyl) (alkyl) amino, aralkylcarbonylamino, (Aralkylcarbonyl) (alkyl) amino, alkyl carbonylamino- alkyl, cicloalquilcarbonilaminoalquilo, carbonylaminoalkyl alkoxy-, (alkylcarbonyl) (alkyl) - aminoalkyl, aralquilcarbonilaminoalquilo, ciclilcarbonilaminoalquilo hetero-, (aralkylcarbonyl) - (alkyl) aminoalkyl, arylsulfonylamino, alkyl - sulfonylaminoalkyl, ureido, monoalquilureido, monohaloalquilureido, dialkylureido, ureidoalkyl, monoalquilureidoalquilo, dialquilureidoalquilo, monohaloalquilureidoalquilo, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl and. An even more preferred method is that method which comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (Ib) wherein: R4 is -0-; Rs is methylene; and R6 is -C (0) -. The most preferred method is that method which comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (Ib) wherein R2 is one plus substituents that are independently selected from the group consisting of hydrogen and halo; R3 is phenyl optionally substituted by one or more substituents independently from the group consisting of hydrogen, hydroxy, halo, alkyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, aminoalkoxy, cycloalkyl, cycloalkylaminoalkyl, aralkyl, hydroxyalkyl selected, ( monoalkylamino) aralkyl, alkoxyalkyl, amino, monoalkylamino, dialkylamino, monoaralkylamino, alkylcarbonylamino, alkenyl-carbonylamino, cycloalkylcarbonylamino, arylcarbonyl-amino, heterocyclylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbonyl) (alkyl) -amino, alkyl sulfonylamino, aminoalkyl , monoalkylaminoalkyl, dialkylaminoalkyl, aminoalkyl or monoaryl, monoaralquilaminoalquilo, alkylcarbonylaminoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl) (alkyl) aminoalkyl, (cycloalkylalkyl) aminoalkyl, alkoxycarbonylaminoalkyl, alcoxicarbonilalquilcarbanilaminoalquilo, (alcoxicarboni l) (alkyl) aminoalkyl, onilaminoalquilo alquilsulf, (alkylsulfonyl) (alkyl) aminoalkyl, onilaminoalquilo arilsulf (arilsulf onyl) (alkyl) -aminoalkyl, heterocyclylaminoalkyl, carboxy, alkoxycarbonyl, alkylcarbonyl, (hydroxyalkoxy) carbonyl, aminocarbonyl, monoalkylaminocarbonyl , monoarylaminocarbonyl, (aminocarbonylalkyl) -aminocarbonyl, (aminoalkyl) aminocarbonyl, (hydroxyalkyl) aminocarbonyl, dialkylaminocarbonylalkyl, hydroxyamidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, (monoalkyl) - (monoaryl) ureido, (haloalkylcarbonylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl) - (alkyl) ureidoalkyl, (alkoxycarbonylalkyl) -ureidoalkyl, glycinamide, monoalkylglycine-amido, aminocarbonylglycinamide, (alkoxyalkylcarbonyl) glycinamide, (aminocarbonyl) (alkyl) -glycinamide, (alkoxycarbonylalkylcarbonyl) (alkyl) glycinamide, (alkoxycarbonyl-aminoalkylcarbonyl) glycinamide, arylcarbonylglycinamido, ( arylcarbonyl) (alkyl) glycinamide, (monoaralkylaminocarbonyl) glycinamide, (monoaralkylaminocarbonyl) (alkyl) glycinamide, (monoarylaminocarbonyl) glycinamide, (monoarylaminocarbonyl) (alkyl) glycinamide, alaninamide, heterocyclyl and heterocyclylalkyl. which comprises adm administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (Ib) which is selected from the group consisting of the following compounds: 1- ((3,4,5-trimethoxy-enoxo) methyl) carbonyl-4- (benzyl) piperazine; 1- ((3,5-dimethoxyphenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2- (hydroxymethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-iodoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methyl) phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((4-methyl) enoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2,4-dichloro-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((4-bromo-2-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, -1- ((4-chloro-3-nitrophenoxy) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine , - 1- ((2-bromofenoxi) methyl) carbonyl -4- (4-chlorobenzyl) piperazine, - 1- ((4-bromofenoxi) methyl) carbonyl -4- (benzyl) piperazine, 1- ((2 , 4-dibromofonoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2-f ormilf enoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, - 1- ((2-methoxy-5-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, - 1- ((3, 4, 5-trimethoxyphenoxy) methyl) carbonyl-4 - (4-f luorobenzyl) iperazine; 1- ((4-chloro-enoxy) ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-chloro-enoxy) ethyl) carbonyl-4- (4-f luorobenzyl) piperazine; 1- ((3-fluoro-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3,5-dimethoxy-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-Bromo-2-formylphenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine. 1- ((3-formyl ^ 4 -nitro phenoxy) methyl) carbonyl-4- (4-f luorobenzyl) piperazine; 1 - ((2-aminocarbonyl-4-chlorophenoxy) methyl) carbonyl-4- (4-f luorobenzyl) piperazine, -1- ((3,5-dimethoxy-4-bromophenoxy) methyl) carbonyl-4- (4- f luorobenzyl) piperazine; and 1- ((2-acetylaminophenoxy) methyl) carbonyl-4- (4-f luorobenzyl) iperazine.

Preparation of the Compounds of the Invention The following Reaction Schemes are directed to the preparation of compounds of formula (la), of formula (Ib) and formula (le). It is understood that these compounds of the invention which are not specifically prepared in the following Reaction Schemes can be prepared by a similar synthesis process with the initial materials and reagents appropriately substituted. It is also understood that in the following descriptions, the combination of various substituents (e.g. Rl, R2 and R3 substituents) of the formulas shown is permissible only if such combinations result in stable compounds. For purposes of convenience only, the preparation of compounds of the invention wherein R3 is solely phenyl are illustrated below. It is understood that other R3 groups (including 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) can be protected in the intermediate compounds used in the preparation, as needed, by means of the appropriate protecting group by treating the intermediate compound before the desired reaction with the appropriate protecting group precursor by methods known to those of ordinary skill in the art. The protecting groups can then be removed as desired by methods known to those of ordinary skill in the art, for example, by acid or basic hydrolysis. Such 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, dimethylpiperazine can be prepared in an asymmetric synthesis according to the method set forth in Mickelson, J.W., Belonga, K.L., Jacobsen, E.J., Journal of Organic Chemistry (1995). Vol. 60, p. 4177-4123. It should be noted that the only difference in the two groups of compounds encompassed by formula (la) and formula (Ib) as described above in the Brief Description of the Invention is the required substitution of the piperazine ring in the compounds of formula (the) . Accordingly, it is understood that, unless otherwise indicated, the following Reaction Schemes directed to the preparation of the compounds of formula (Ia) can be used to prepare compounds of formula (Ib), and the following Reaction Schemes directed for the preparation of the compounds of formula (Ib) can be used to prepare compounds of formula (la).

In addition, the compounds of formula (Id) can be prepared in a manner similar to those described herein for the compounds of formulas (la) and (Ib).

A. Preparation of Compounds of Formula (C) The compounds of formula (C) are intermediates in the preparation of the compounds of the invention. were prepared according to the following Reaction Scheme 1 wherein Rlal is one or more substituents Rl independently selected as described above em Brief Description of the Invention for compounds of formula (Ia) (except that Rlal can not be aminoalkyl or monoalkylaminoalkyl unless appropriately protected); X is chlorine, bromine or iodine; and R2 is as described above for compounds of formula (la): Reaction Scheme 1 (A) (B) (C) The compounds of formula (A) and of formula (B) are commercially available, for example, from Aldrich Chemical Co. or Sigma Chemical Co., or can be prepared according to methods known to those usually familiar with the art. In general, compounds of formula (C) can be prepared by treating a compound of formula (A) in an organic solvent, such as methylene chloride, with an equimolar amount of a compound of formula (B). The reaction mixture is stirred for about 10 to 20 hours at room temperature. The reaction mixture is then concentrated to provide a residue which is dissolved in an organic solvent. The compound of formula (C) is isolated from the solution by standard isolation techniques, for example, by filtration, concentration and flash column chromatography.

B. Preparation of the Compounds of Formula (Ga) and Formula (Gb) The compounds of formula (Ga) and of formula (Gb) are intermediates in the preparation of the 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, f or i1 alk i1 or, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy) aralkyl, (hydroxy) cycloalkylalkyl, mercaptoalkyl, cyanoalkyl, haloalkylcarbonylamino-alkyl, (alkoxy) aralkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthioalkyl, inilalquilo alquilsulf, onilalquilo alquilsulf, hydroxyalkylthioalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, monoar ylamino -alkyl, monoaralquilaminoalquilo, alkylcarbonylaminoalkyl, (alkylcarbonyl) (alkyl) aminoalkyl, ureidoalkyl, monoalquilureidoalquilo, gave the qui lur qu i ei DOAL one or at coxi carb onyl aminoalqui so, the hydroxyalkyl aminoalqui , aryloxyalkyl carbonyl oxyalkyl, alcoxialquilcarboniloxialquilo, coxi to qu aral i 1 carboni 1 oxy to chyle, alkylcarbonylalkyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarilaminocarbonilalquilo, monoaralkyl aminocarbonyl or, heterocyclyl and heterocyclylalkyl (except that Rlal can not be aminoalkyl or monoalkylaminoalkyl to unless properly protected): Reaction Scheme 2 (D) < E) (F) (F) The compounds of formula (D) and of formula (E) are commercially available, for example, from Aldrich Chemical Co. or Sigma Chemical Co. , or can be made from methods known to those usually familiar in the art. In general, the compounds of formula (Ga) and formula (Gb) are prepared by first treating 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 during a period of two hours. The resulting reaction mixture is stirred for about 2 to 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 product concentration and purification by vacuum distillation. To a solution of a strong reducing agent, such as lithium aluminum hydride, in an anhydrous polar aprotic solvent, such as tetrahydrofuran, the compound of formula (F) is added. The resulting mixture is stirred at room temperature for about 30 minutes to about 2 hours, preferably for about 1 hour. The mixture is then heated to reflux to complete the reaction. At the time it is complete, the compound of formula (Ga) is isolated from the reaction mixture by standard isolation techniques, such as suspension by water and a moderate base, followed by filtration. Alternatively, to a solution of formula (F) in a polar protic solvent, such as absolute ethanol, a solid alkali metal, such as sodium metal, is added over a period of time, such as for example over a period of 3 hours. The resulting mixture is heated to reflux for about 2 to about 4 hours, preferably for about 3 hours. The compound of formula (Gb) is distilled from the reaction mixture by the addition of water to the reaction mixture. The distillate is then treated with an aqueous acid, such as 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 Esquema 1 to produce the compounds of the invention wherein the relative orientation of the Rla substituents is fixed.

C. Preparation of Formula Compounds (the) The compounds of formula (la) 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 Rla substituents independently selected as described above in the Brief Description of the Invention for compounds of formula (la) (except that Rlal can not contain a primary or secondary amine unless appropriately protected), - R2, R4 and Rs are as described in the brief description of the invention for compounds of formula (la) (except that R4 and R5 can not contain a first or secondary amine unless adequately protected), and R3a is one or more substituents independently selected from the group consisting of hydrogen, hydroxy, onyl hidroxisulf, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, ynyl alquilsulf, onyl alquilsuf, alkylthioalkyl, inilalquilo alquilsulf, onilalquilo alquilsulf, alkoxy, aryloxy, haloalkyl, formyl, ormilalquilo f , nitro, nitroso, cyano, aralkoxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, (Hydroxy) cycloalkylalkyl, cycloalkylamino, cycloalkylaminoalkyl, (cycloalkylalkyl) amino, (cycloalkylalkyl) -aminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy) aralkyl, hydroxyalkylthioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (the coxi ) aralkyl or ar iloxialquil or, aralkoxyalkyl, amino, monoalkylamino, dialkylamino, amino monoar i 1, 1 monoaralqui amino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, hydroxyalkylaminoalkyl, monoarilaminoalquilo, monoaralquilaminoalquilo, 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, aral coxicarbonil alkyl or at loxialquil carboni coxialquil or, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, monoarilaminocarbonilo, monoaralkyl aminocarbonyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylaminocarbonylalkyl, monoaralkylaminocarbonylalkyl, amidino, guanidino, ureido, monoalkylureido, dialkyluride, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, heterocyclyl and heterocyclylalkyl; and R4 and Rs are as described in the Brief Description of the Invention: Reaction Scheme 3 (H) (J) () (B) (la) The compounds of formula (B), of formula (H) and of formula (J) are commercially available, for example from Aldrich Chemical Co. or Sigma Chemical Co., or can be prepared according to methods known to those usually familiar in the art. In general, compounds of formula (la) are prepared by the following Reaction Scheme above when first preparing a compound of formula (H) in a polar solvent such as methanol, with an equimolar amount of a compound of formula (J) in an anhydrous polar solvent, such as anhydrous ether. The resulting reaction mixture is stirred at room temperature for about 5 minutes to about 24 hours in the presence of an acid scavenger base, such as triethylamine. The compound of formula (K) is then isolated from the reaction mixture by standard isolation techniques, such as extraction in organic phase, evaporation of solvents and purification by flash column chromatography. The compound of formula (K) in a polar aprotic solvent, such as tetrahydrofuran, is treated with an excess molar amount of a compound of formula (B) in the presence of a moderate base, such as triethylamine, and optionally, a catalytic amount of sodium iodide. The resulting mixture is stirred at room temperature for about 1 to 5 days, preferably for about 2 days. The compound of formula (la) is then isolated from the reaction mixture by standard isolation techniques such as filtration, concentration of volatiles and purification by flash chromatography. Alternatively, the compounds of formula (Ga) and of formula (Gb), as prepared above in Reaction Scheme 2, can be used in place of compounds of formula (H) in this reaction scheme to produce compounds of the invention wherein the relative orientation of the substituents Rla is fixed.

D, Preparation of Formula Compounds (the) The compounds of formula (la) are compounds of the invention and are prepared as illustrated in the following Reaction Scheme 4, wherein X is chloro, bromo or an activated ester; P1 and P2 are independently nitrogen protecting groups, such as t-butoxycarbonyl (P1 may also be hydrogen); Rla, R2, R4 and Rs are as described above in the Brief Description of the Invention; Rlb is as defined above in the Brief Description of the Invention for compounds of formula (le) and (Id); and R3a is one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alguilo, mercapto, mercaptoalguilo, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, aryloxy, haloalkyl, formyl, for ilalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy) cycloalkylalkyl cycloalkylamino, cycloalkylaminoalkyl (Cycloalkylalkyl) amino, (cycloalkylalkyl) aminoalkyl cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl aralkenyl, hydroxyalkyl, (hydroxy) aralqui one or hydroxyalkylthioalkyl, hydroxyalkenyl, alkoxyalkyl hydroxyalkynyl, (the coxi) aralkyl, ar iloxialquilo aralkoxyalkyl, amino, monoalkylamino, dialkylamino monoar i1 amino, monoaralqui one amino, aminoalkyl monoalkylaminoalkyl, dialkylaminoalkyl hydr oxy to qu i 1 i 1 aminoalqu or monoar qu i 1 i 1 ami NOAL or monoaralquilaminoalquilo, alkylcarbonylamino (alkylcarbonyl) (alkyl) amino, alkylcarbonylaminoalkyl (alkylcarbonyl) (alkyl) aminoalkyl, alkoxycarbonylamino (alkoxycarbonyl) (alkyl) amino, alkoxycarbonylaminoalkyl (Alkoxycarbonyl) (alkyl) aminoalkyl, carboxy, aralkoxycarbonyl alkoxycarbonyl, alkylcarbonyl, alkylcarbonylalkyl arylcarbonyl, arylcarbonylalkyl, aralquilcarbonilalquilo aralkylcarbonyl, carboxyalkyl, aralkoxycarbonylalkyl alkoxycarbonylalkyl, alcoxialquilcarboniloxialquilo aminocarbonyl, monoalkylaminocarbonyl, monoaryl dialkylaminocarbonyl aminocarbonyl, monoaralqui I amino carboni the aminocarbonylalkyl, monoaiquil aminocarbonyl alkyl or dialkylaminocarbonylalkyl, I monoarilaminocarbonilalquilo monoaralquilaminocarbormalquilo, amidino, guanidino, ureido monoalquilureido, dialquilur eido, ureidoalkyl, monoalquilureidoalquilo, dialquilureidoalquilo, heterocyclyl and heterocyclylalkyl; Reaction Scrub 4 () (M) (DO NOT) Reaction Run 4 (continued) (the) The compounds of formula (L) of formula (N), of formula (P) and of formula (J) are commercially available, for example, from Aldrich Chemical Co. or Sigma Chemical Co., or can be prepared according to methods known to one of ordinary skill in the art. The compounds of formula (L) in which the Rlb substituent contains an unprotected hydroxy group can be protected with an appropriate oxygen protecting group prior to the synthesis of the compound of formula (M). The removal of the protecting group can be carried out as desired. In general, compounds of formula (la) are prepared by first esterifying a compound of formula (L) by treating the compound with an excess molar amount of a lower alkanol, preferably methanol, in the presence of an acid, preferably a hydrochloride, at about 0 ° C to room temperature. The resulting mixture is then stirred at about 0 ° C to the reflux temperature, preferably at room temperature for about 4 hours to about 18 hours. The mixture is then concentrated by solvent removal to yield the compound of formula (M). To a solution of the compound of formula (M) in an organic solvent, such as methanol, at about 0 ° C to room temperature, a molar excess amount of a compound of formula (N) is added and then treated with a moderate acid, such as acetic acid, and stirred at room temperature for about 2 hours to about 4 hours, preferably about 3 hours, to form an intermediate imine. 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 flash column chromatography. To a solution of the test compound (P) in a polar aprotic solvent, such as anhydrous tetrahydrofuran, a moderate acid scavenger base, such as N-methylmorpholine, is added, followed by the addition of an acid coupling reagent, such as chloroformate. of isobutyl. The resulting mixture is stirred at about 0 ° C to room temperature for about 15 minutes to about 2 hours, preferably about 15 minutes at 0 ° C and then for about one hour at room temperature, to form an active ester intermediate of the compound of formula (P). The intermediate is then treated in situ with a compound of formula (O) in an anhydrous polar aprotic solvent, such as anhydrous tetrahydrofuran, and the resulting mixture is stirred at room temperature for about 10 hours to 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 in organic phase and purification by flash column chromatography. The compound of formula (Q) in an aprotic solvent, such as methylene chloride, at about 0 ° C, is then treated with a strong organic acid, such as trifluoroacetic acid, for a period of from about 2 to about 4 hours, preferably for 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 isolated in the reaction mixture by standard isolation techniques, such as neutralization with a moderate base, filtration and concentration. The compound of formula (R) in an anhydrous polar aprotic solvent, such as anhydrous tetrahydrofuran, at about 0 ° C, is treated with a strong reducing agent, such as lithium aluminum hydride. The resulting mixture is then heated to reflux for about 12 hours to about 24 hours, preferably for about 15 hours. The mixture is then cooled to room temperature and the reaction is suspended with water, followed by an aqueous base, preferably aqueous potassium hydroxide. The resulting mixture is allowed to stir at room temperature for about 30 minutes to one hour. The compound of formula (S) is then isolated from the reaction mixture by filtration and concentration. The test compound (S) in a polar aprotic solvent, such as methylene chloride, in the presence of an excess amount of an acid scavenger base, such as triethylamine, is added a slightly excess polar amount of a compound of formula (J) in a polar aprotic solvent, such as methylene chloride. The resulting mixture is stirred at room temperature for about 15 minutes to about 1 hour, preferably about 15 minutes. The compound of formula (la) is then isolated from the reaction mixture by standard isolation techniques, such as extraction, concentration and flash column chromatography.

E. Preparation of the Compounds of Formula (Ib) The compounds of formula (Ib) are compounds of the invention and are prepared as illustrated below in the following Reaction Scheme 5, wherein X is chloro, bromo, -Rlb is as defined above in the Brief Description of the Invention for compounds of formula (le) and of formula (Id); and R2 is as described above in the Brief Description of the Invention for compounds of formula (Ib); 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, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, carboxyalkyl, alkoxycarbonylalkyl, aryloxycarbonylalkyl, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, arylsulfonyl, hydroxyalkoxy , aminoalkoxy, (monoalkylamino) aralkyl, aminoalkylamino, heterocyclylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocycliclcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, lcoxycarbonylalkylcarbonylamino, at 1 qui 1 su 1 foni 1 ami no, ari 1 carb on i 1 ami nia 1 qui 1 o, alkoxycarbonylalkyl carbonyl minoalkyl, alkylsulfonyl-aminoalkyl, (alkyl sui fonyl) (alkyl) aminoalkyl, arylsulphonylaminoalkyl , (arylsulf onyl) (alkyl) aminoalkyl, het erocicl ilaminoalkyl, (hydroxyalkoxy) carbonyl, (aminocarbonylalkyl) aminocarbonyl, (monoalkylaminocarbonylalkyl) aminocarbonyl, (carboxyalkyl) -aminocarbonyl, (alkoxycarbonylalkyl) aminocarbonyl, (aminoalkyl) aminocarbonyl, (hydroxyalkyl) aminocarbonyl, dialkylaminocarbonyloxyalkyl, monoarylureido, monoaralkylureido, monohaloalkylureido, (monoalkyl) (monoaryl) ureido, diarylureido, (haloalkylcarbonyl) ureido, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl) (alkyl) ureidoalkyl, (alkoxycarbonylalkyl) -ureidoalkyl, glycinamide, monoalkylglycinamide, (alkoxyalkylcarbonyl) glycinamide, aminocarbonylglycinamide, (aminocarbonyl) (alkyl) glycinamide, (alkoxycarbonylalkylcarbonyl) (alkyl) glycinamide, (alkoxycarbonylaminoalkylcarbonyl) glycinamide, arylcarbonylglycinamide, (arylcarbonyl) - (alkyl) glycinamide, (monoaralkylaminocarbonyl) glycinamide, (anoaralkylaminocarbonyl) (alkyl) glycinamide, ( monoarylaminocarbonyl) glycinamide, (monoarylaminocarbonyl) (alkyl) glycinamide, glycosylamidoalkyl, alaninamide, monoalkylalaninamide, alaninamidoalkyl, heterocyclyl and heterocyclylalkyl; and R4a is -O- or -N (R7a) where R7a is hydrogen, alkyl, aryl or aralkyl: Reaction Scheme 5 (T) (Ib) The compounds of formula (U) are commercially available, for example, from Aldrich Chemical Co. or Sigma Chemical Co. , or can be prepared according to methods known to those usually familiar in the art. The compounds of formula (T) can be prepared according to the methods described herein for compounds of formula (C) or for compounds of formula (K) or by acylation of the compounds of formula (C) as prepared in the present, by standard methods known to those usually familiar in the art. In general, the 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, with a slightly excess molar amount of a compound of formula (U) in the presence of a moderate base such as potassium carbonate. The resulting mixture is stirred at about 50 ° C for about 10 hours to 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) The compounds of formula (Ib) can be prepared as illustrated in the following Reaction Scheme 6, wherein X is chloro, bromo or an activated ester; P1 is a nitrogen protecting group such as t-butoxycarbonyl; R1b is as described above in the Brief Description of the Invention for the compounds of formula (le) and of formula (Id), - R2a is as described above in the Brief Description of the Invention for R2 in compounds of formula [ ), except that Ra can not be formyl-alkyl formyl; R3a is one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alquilsulfininilo, alkylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, aryloxy, haloalkyl, formyl, formylalkyl , nitro, nitroso, cyano, aralkoxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy) cycloalkylalkyl, cycloalkylamino, cycloalkylamino alkyl, (cycloalkylalkyl) amino, (cicloalquialquil) aminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy) aralkyl, hydroxyalkyl-thioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy) aralkyl, aryloxyalkyl, aralkoxyalkyl, amino, monoalkylamino, dialkylamino, monoarylamino, monoaralkylamino, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, hydroxyalkylaminoalkyl, monoarylaminoalkyl, monoaralkylaminoalkyl, alky ylcarbonylamino, (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, alcoxialquilcarbonil oxy to chyle, aminocarbonyl, monoalkylated inocarbonilo, dialkylaminocarbonyl, monoarilaminocarbonilo, monoaralkyl aminocarbonyl or aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarilaminocarbonilalquilo, monoaralquilaminocarbonilalquilo, amidino, guanidino, ureido, monoalquilureido, dialkyluride, ureidoalkyl, monoalkylureidoalkyl, dialkyl ureidoalkyl, heterocyclyl and heterocyclylalkyl; and R4 is -0-, or -N (R7a) - wherein R7 is hydrogen, alkyl, aryl or aralkyl: Reaction Scroll 6 (V) (U) (W) The compounds of formula (U) and formula (N) are commercially available, for example, from Aldrich Chemical Co., or Sigma Chemical, Co. , or can be prepared according to methods known to those usually familiar in the art. The compounds of formula (V) can be prepared according to the method described above for compounds of formula (K) in Reaction Scheme 3. In general, compounds of formula (Ib) as prepared in Reaction Scheme 6 above, are prepared by first treating a compound of formula (U) in an aprotic solvent such as dimethylformamide, at about 0 ° C with a strong base such as potassium hexamethyldisilazide to deprotonate the compound. The resulting mixture is stirred for about 20 minutes to one hour, preferably for about 20 minutes, at about 0 ° C. An equimolar amount of a compound of formula (V) in an aprotic solvent, such as dimethylformamide, is then added to the mixture and the resulting mixture is stirred at room temperature for about 1 to about 24 hours, preferably for about 2 hours . The compound of formula (W) is then isolated from the reaction mixture by standard isolation techniques, such as extraction and concentration. The protecting group P1 is then removed from the compound of formula (W) to form a compound of formula () by standard amine deprotection procedures, such as treating the compound of formula (W) with a strong acid, such as trifluoroacetic acid. To a solution of the compound of formula (K) in a polar solvent, such as methanol, at about 0 ° C to room temperature, an excess molar amount is added in a compound of formula (N), and then treated with a moderate acid, such as acetic acid, and stirred at room temperature for about 2 hours to about 4 hours, preferably for about 3 hours, to form an intermediate imine. The imine is then reduced in situ by treatment with a reducing agent such as sodium cyanoborohydride, to produce a compound of formula (Ib), which is isolated from the reaction mixture by standard isolation techniques, such as filtration and purification by instant column chromatography.

G. Preparation of the Compounds of Formula (Ib) The compounds of formula (Ib) can also be prepared as illustrated in the following Reaction Scheme 7, wherein R 1b is as described above in the Brief Description of the Invention, for compounds of formula (le) and formula (Id. ); and R2 is as described above in the Brief Description of the Invention for the compounds of formula (Ib): and R3a is one or more substituents that are independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, mercapto alkyl , mercaptoalkyl, alkylthio, alkylsulfonyl, alkylsuf onyl, alkylthioalkyl, alkylsulphonylalkyl, alkylsulphonylalkyl, alkoxy, aryloxy, haloalkyl, formyl, orylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy cycloalkyl, cycloalkylalkyl, (hydroxy) cycloalkylalkyl cycloalkylamino, cycloalkylaminoalkyl (cycloalkylalkyl) amino, (cycloalkyalkyl) aminoalkyl cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl aralkenyl, hydroxyalkyl, (hydroxy) arkyl or hydroxyalkyl thioalkyl, hydroxyalkenyl, hydroxyalkynyl alkoxyalkyl, (alkoxy) aralkyl, aryloxyalkyl aralkoxyalkyl, amino, monoalkylamino, dialkylamino monoar il amino, monoaralkyl 1 amino, aminoalkyl monoalkylaminoalkyl, dialkylaminoalkyl hydroxyalkylaminoalkyl, monoarylaminoalkyl monoaralkylaminoalkyl, alkylcarbonylamino (alkylcarbonyl) (alkyl) amino, alkylcarbonylaminoalkyl (alkylcarbonyl) (alkyl) aminoalkyl, alkoxycarbonylamino (alkoxycarbonyl) (alkyl) amino, alkoxycarbonylaminoalkyl (Alkoxycarbonyl) (alkyl) aminoalkyl, carboxy, aralkoxycarbonyl alkoxycarbonyl, alkylcarbonyl, alkylcarbonylalkyl arylcarbonyl, arylcarbonylalkyl, aralquilcarbonilalquilo aralkylcarbonyl, carboxyalkyl, alkoxycarbonylalkyl aralkoxy carbonyl to chyle, alcoxialquilcarboniloxialquilo, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, monoarilaminocarbonilo, monoaralqui lamino carboni it, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylaminocarbonylalkyl, manuaralkylaminocarbonylalkyl, amidino, guanidino, ureido, monoalkylureido, dialkyluride, ureidoalkyl, manalkylureidoalkyl, dialkylureidoalkyl, heterocyclyl and heterocyclylalkyl: Reaction Scheme 7 (X) (Y) (C) - (Ib) The compounds of formula (X) are commercially available, for example, from Aldrich Chemical Co. or Sigma Chemical Co., or can be prepared according to known methods by those known 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 by this Reaction Scheme are prepared by first treating a compound of formula (X) in an organic solvent, such as toluene, with phosgene for a period of time from about 1 hour to about 24 hours, preferably for 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 formula (Y) in an aprotic polar solvent, such as tetrahydrofuran, is then treated with an equimolar amount of a compound of formula (C). The resulting mixture is stirred at room temperature for about 10 hours to about 48 hours, preferably for about 20 hours. The compound of formula (Ib) is then isolated from the reaction mixture by standard isolation techniques, such as concentration and evaporation of the solvents.

H. Preparation of Formula Compounds (le) The compounds of formula (le) are compounds of the invention and are prepared as illustrated in the following Reaction Scheme 8, wherein Y is bromine, chlorine or iodine; and Rlb, R2, R3, R4, R5, Rs and R9 are as described in the above in the Description Brief of the Invention for compounds of formula (le): Reaction Scheme 8 The compounds of formula (Ib) are prepared as described herein, and compounds of formula R9Y are commercially available, for example, from Aldrich Chemical Co. or Sigma Chemical Co., or can be prepared according to known methods by those usually familiar with the technique. In general, compounds of formula (le) are prepared by first treating a compound of formula (Ib) in a non-polar organic solvent, such as toluene, with an excess molar amount of a compound of formula R9Y. The resulting mixture is stirred at room temperature for about 1 to 10 days, preferably for about 6 days. The compound of formula (le) precipitates from the solution as the quaternary salt and is isolated by standard isolation techniques such as filtration. The counterion can be exchanged with other counterions by methods known to those usually familiar in the art. In addition to the above Reaction Schemes 1 to 8, other compounds of the invention can be made by reactions known to those familiar with the art. For example, a compound of formula (la), of formula (Ib), of formula (le) or of formula (Id), or any initial material or intermediary thereof, appropriately substituted, wherein at least one substituent Rla or at least one Rlb substituent is selected from the group consisting of hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy) aralkyl, (hydroxy) cycloalkylalkyl, hydroxyalkylthioalkyl and hydroxyalkylaminoalkyl, can be dissolved in a polar aprotic solvent such as methylene chloride, in the presence of a moderate acid scavenger base, and then treated with a slightly excess molar amount of sulfonyl halide, such as sulfonyl chloride, to form an intermediate compound containing a sulphonate leaving group. The compound can then be dissolved in an anhydrous aprotic solvent, such as dimethylformamide, and treated, in the presence of a moderate base, with an appropriate nucleophilic reagent to form the compounds of formula (la), of formula (Ib) or of formula (le) or any initial material appropriately substituted or intermediary thereof, wherein the Rla substituent or the Rlb substituent (depending on the nucleophilic reagent used) can be selected from the group consisting of heterocyclylalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, cycloalkylamino, cyanoalkyl, ( ci alkalkyl 1 alky1) aminoalkyl or hydroxyalkylthioalkyl. Alternatively, a compound of formula (la), formula (Ib), formula (le) or formula (Id) or any initial material or intermediary thereof appropriately substituted, which contains a hydroxy group, such as hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl , (hydroxy) aralkyl, (hydroxy) cycloalkylalkyl, hydroxyalkylthioalkyl and hydroxyalkylaminoalkyl can be treated with a moderate oxidizing agent, such as oxalyl chloride, which is dissolved in an inert organic solvent, such as methylene chloride, to which is added DMSO for a period of time from about -60 ° C to about 0 ° C, preferably about -50 ° C. The reaction mixture is stirred at about -60 ° C to about 0 ° C for about 15 minutes to about an hour, preferably about 15 minutes, and then a moderate base such as triethylamine is added to the mixture. The mixture is allowed to gradually warm to room temperature, at which point the oxidized compound (ie, the corresponding aldehyde) of formula (la), formula (Ib), formula (le) or formula (Id), or the initial material or intermediary thereof substituted appropriately, it is isolated from the reaction mixture by standard isolation techniques. Alternatively, a compound of formula (la), formula (Ib), formula (le) or formula (Id), or any initial material appropriately substituted or intermediary thereof, which contains an aldehyde or ketone group, such as formyl, alkylcarbonyl or alkylcarbonylalkyl can be treated with the organometallic reagent or such as organomagnesium or organolithium, under standard Grignard synthesis reaction conditions to form the corresponding hydroxy-substituted compounds. Alternatively, a compound of formula (la), formula (Ib), formula (le) or formula (Id), or any initial material appropriately substituted or intermediary thereof, which contains a hydroxy group such as hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy) aralkyl, (hydroxy) cycloalkylalkyl, hydroxyalkylthioalkyl and hydroxyalkylaminoalkyl in an anhydrous polar solvent, such as anhydrous ether, in the presence of a strong base, such as sodium hydride, can be treated with an alkyl halide such as methyl iodide, at room temperatures, to form the substituted compounds with corresponding alkoxy. Alternatively, a compound of formula (la), formula (Ib), formula - (le) or formula (Id), or any initial material appropriately substituted or intermediary thereof, wherein at least one R la substituent or so. unless a Rlb substituent is formyl or formylalkyl, it can be reacted with a primary or secondary amine, under the conditions of reductive amination as described above for the preparation of the compounds of formula (O) or the compounds of formula (Ib) as are repeated in Reaction Scheme 6 to form the corresponding compounds of formula (la), formula (Ib), formula (le) or formula (Id), or any initial material appropriately substituted or intermediary thereof, wherein the substituent Rla or the Rlb substituent is monoalkylaminoalkyl, dialkylaminoalkyl, monoaralkylaminoalkyl or hydroxyalkylaminoalkyl. Alternatively, a compound of formula (la), formula (Ib), formula (le) or formula (Id) or any initial material appropriately substituted or intermediary thereof, which contains an ester group, such as an alkoxycarbonyl, aryloxycarbonyl or aralkoxycarbonyl, can be subjected to standard basic hydrolysis conditions, to form the corresponding compound of formula (la), formula (Ib), formula (le) or formula (Id), or any initial material appropriately substituted or intermediary thereof, which contains an acid group, that is, a carboxy group. Alternatively, a compound of formula (la), formula (Ib), formula (le) or formula (Id), or any initial material appropriately substituted or intermediary thereof, wherein Rs is -C (0) - can be reduced to the corresponding compound of formula (la), formula (Ib), formula (le) or formula (Id), or any initial material appropriately substituted or intermediary thereof, wherein Rs is -CH2- by methods known to those usually familiar in the art, for example, by the method described above for the compounds of formula (S). In addition, the compounds of formula (la), formula (Ib), formula (le) or formula (Id), or any initial material appropriately substituted or intermediary thereof, wherein Rs is -C (0) - can be converted to a compound of formula (la), formula (Ib), formula (le) or formula (Id), or any initial material appropriately substituted or intermediary thereof, wherein Rs is -C (S) - by treatment with the Lawesson's reagent under standard conditions known to those commonly known in the art. In addition, the compounds of formula (la), formula (Ib), formula (le) or formula (Id), or any initial material appropriately substituted or intermediary thereof, which contains a non-oxidized sulfur atom, can be oxidized with the appropriate sulfur oxidizing agent according to the methods known to those familiar in the art, for example by the use of hydrogen peroxide, to produce the corresponding compounds which contain a sulfinyl group or a sulfonyl group instead thereof. Alternatively, the compounds of formula (Ia), formula (Ib), formula (le) or formula (Id), or any initial material appropriately substituted or intermediary thereof, which contains a carboxy group can be converted to compounds containing the corresponding amide group by first converting the carboxy group to an activated ester or mixed anhydride using, for example, isobutyl chloroformate, in the presence of a moderate base, such as N-methylmorpholine, in an aprotic solvent, such as THF, and then treating the ester with an appropriately substituted primary or secondary amine, in an aprotic solvent, such as THF. Alternatively, the compounds of formula (Ia), formula (Ib), formula (le) or formula (Id), or any initial material appropriately substituted or intermediary thereof, which contains a cyano group, can be converted to the compounds contain a hydroxyamidino group by reaction with hydroxyamine in a polar solvent, such as DMSO. Hydroxyamine can be prepared in situ by first treating hydrochloride salt of hydroxyamine with a base, such as triethylamine.

Alternatively, of formula (la), formula (Ib), formula (le) or formula (Id), or any initial material appropriately substituted or intermediary thereof, which contains a hydroxy group can be converted to compounds containing a group azide corresponding to treating the compound with triphenylphosphine and an alkyl azidocarboxylate, for example diethyl azodicarboxylate, in an aprotic solvent, such as THF, and then displacing the activated oxygen formed in this manner with the azide source, such as diphenylphosphoryl azide, in an aprotic solvent, such as THF. Alternatively, the compounds of formula (la), formula (Ib), formula (le) or formula (Id), or any initial material appropriately substituted or intermediary thereof, which contains an -NH2 group or a -Ra-NH2 group it can be converted to compounds containing a corresponding -Ra-N (H) -C (O) - group by reacting the group with an appropriately substituted acid halide under standard acylation conditions. Alternatively, the compounds of formula (Ia), formula (Ib), formula (le) or formula (Id), or any initial material appropriately substituted or intermediary thereof, which contains an acid halide group (-C (O)) -X wherein X is halo) or an activated ester group, can be converted to compounds containing the group -C (0) -N (H) - by reacting the compound with the primary or secondary amine appropriately substituted under the conditions of formation of a standard amide or acylation union. Alternatively, the compounds of formula (Ia), formula (Ib), formula (le) or formula (Id), or any initial material appropriately substituted or intermediary thereof, which contains a primary or secondary amine group, can be converted to compounds containing the corresponding aminoalkyl group in a manner similar to the conversion of formula (M) to formula (0) in Reaction Scheme 4. In particular, the amine is reacted with an appropriately substituted aldehyde to form the intermediate imine, which is then reduced by treatment with an appropriate reducing agent, such as sodium cyanoborohydride. Alternatively, the compounds of formula (la), formula (Ib), formula (le) or formula (Id), or any initial material appropriately substituted or intermediary thereof, which contains a primary or secondary amine can be converted to the compounds containing the corresponding ureido group by reacting the compound with phosgene in a manner similar to Reaction Escape 7 above (in an aprotic solvent) to form the corresponding isocyanate, which is then reacted with an appropriately substituted primary or secondary amine. In addition, all compounds of the invention that exist in free base or free acid form can be converted to their pharmaceutically acceptable salts by treatment with the appropriate inorganic or organic acid, or by the appropriate inorganic or organic base. The salts of the compounds of the invention can also be converted to the free base form or to the free acid form or to another salt by methods known to those familiar in the art. The following preparations of specific examples are provided as a guide to assist in the practice of the invention, and are not intended to be a limitation on the scope of the invention. In the preparation and examples that follow, all NMR data are defined to the XH NMR spectrum data and are provided in the format "(multiplicity, number of hydrogens)". The yield of each of the reactions described herein is expressed as a percentage of the theoretical yield.

PREPARATION 1 Compound of Formula (C) A. To a solution of 2-methylpiperazine (0.10 g, 1 mmol) in CH2C12 (2 ml) is added 4-fluorobenzyl bromide (0.125 ml, 1 mmol). The resulting mixture is stirred at room temperature. After 15 hours, the mixture is concentrated in vacuo to provide a solid. This solid is dissolved in CH2C12 and washed sequentially with water, aqueous NaHCO3 solution and then with brine. The organic layer is dried over MgSO4, filtered and concentrated to an oil. Purification by flash column chromatography affords 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 (s broad, 2), 1.6 (t, 1), 1.0 (d, 3) ppm.

B. In a similar manner, the following compounds of formula (C) are prepared: (2R, 5S) -1- (chloro) acetyl-4- (4-fluorobenzyl) -2,5-dimethylpiperazin-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. In a similar manner, 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) is added 2,3-butanedione (18.6 g, 216 mmol in 200 ml of anhydrous ether) dropwise for 2 hours. The resulting mixture is stirred at room temperature. After 3 hours, the clear solution is concentrated in vacuo to give a brown oil. Purification by vacuum distillation affords 16.6 g (70% yield) of 5-, 6-dimethyl-2,3-dihydropyrazine, a compound of formula (F) as a clear yellow oil; e.g. 60 ° C / 16 mmHg, NMR (CDC13) 3.3 (broad s, 4), 2.1 (s, 6) ppm.

B. In a similar manner, 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) are cautiously added with 5,6-dimethyl-2,3-dihydropyrazine (1.0 g, 9 mmol in 10 ml of anhydrous tetrahydrofuran). The resulting mixture is stirred at room temperature for 1 hour, and then heated to reflux. After the reaction is completed, as determined by thin layer chromatographic analysis of the reaction mixture, the reaction mixture is cooled to room temperature and suspended by the sequential addition of 0. 4 ml of water, 0.4 ml of a 15% aqueous solution of NaOH and then 1.2 ml of water. After brief agitation, the mixture is filtered through a filtered funnel. The filtrate is concentrated in vacuo to 0.92 g (90% yield) of (cis) -2,3-dimethylpiperazine, a compound of formula (Ga) as a yellow and clear oil; NMR (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 prepared.

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) is added metallic sodium (6.5 g, 280 mmol) in small portions over a period of 3 hours. The resulting mixture is heated to reflux.

After 3 hours at reflux, the product is distilled from the mixture while 200 ml of water are gradually added to the reaction vessel. The distillate is treated with an aqueous 1N HCl solution and concentrated in vacuo to provide a semi-solid. Trituration with acetone gives 0.78 g (20% yield) of (trans) -2, 3-dimethylpiperazine, a compound of formula (Gb) as an orange solid, - NMR (DMSO-de) 9.8 (broad s, 4) , 3.5-3.2 (m, 6), 1.2 (s, 6) ppm.

B. In a similar manner, other compounds of formula (Gb) are prepared.

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) is added 4-chlorophenoxyacetyl chloride (0.205 g, 1.0 mmol, in 6 ml solution of anhydrous ether). ). The resulting mixture is stirred at room temperature for 10 minutes and then triethylamine (0.10 ml, 0.72 mmol) is added. After 30 minutes, the mixture is concentrated in vacuo to provide an oily residue. This is taken up in ether and washed with a saturated aqueous solution of NaHCO 3 and then with brine. The organic layer is separated, dried over MgSO4, filtered and concentrated in vacuo to provide an oil. Purification by flash column chromatography affords 0.202 g (80% yield) of (cis) -1- ((4-chlorophenoxy) methyl) carbonyl-3,5-dimethylpiperazine, a compound of formula (K), as an oil colorless and transparent; 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) are prepared: (3S, 5S) -1- ((4-chlorophenoxy) methyl) carbonyl-3,5-dimethylpiperazine; and (3R, 5R) -1- ((4-chlorophenoxy) methyl) carbonyl-3,5-dimethylpiperazine.

C. In a similar manner, other compounds of formula (K) are prepared.

PREPARATION 6 Compounds of Formula (M) A. A solution of (2R) -3-benzyloxy-2- (N- (t-butoxycarbonyl) amino) clothingnoic acid (23 g, 78 mmol, [a] D -4.4 ° (c = 2, H20) in methanol (250 ml) is cooled to 0 ° C and HCl (g) is bubbled into the solution until saturated. The resulting mixture is stirred at room temperature for 17 hours and then concentrated in vacuo to provide 17 g (100% yield) of the (2R) -3-benzoyloxy-2-aminopropanoic acid methyl ester, a compound of formula (M) ), as a white solid, - NMR (DMSO-ds) 8.7 (broad s, 3), 7.4-7.3 (m, 5), 4.5 (c, 2), 4.4 (s broad, 1), 3.8 (s, 2), 3.7 (s, 3) ppm.

B. In a similar manner, other compounds of formula (M) are prepared.

PREPARATION 7 Compounds of Formula (O) A. A solution of (2R) -3-benzyloxy-2-aminopropanoic acid methyl ester (19 g, 78 mmol) in methanol (350 ml) under N2 is cooled to 0 ° C and acetic acid (2 g, pH 2) 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 3 Á molecular sieves (15 g). The resulting mixture is stirred at room temperature for 3 hours, and then filtered through Celite (MeOH). The filtrate is concentrated in vacuo to provide a clear liquid. This is taken up in ethyl acetate and washed sequentially with a 10% aqueous solution of Na 2 CO 3, water and then brine. The organic phase is then dried over MgSO 4, filtered and concentrated in vacuo. Purification by flash column chromatography on silica gel afforded 14.7 g (60% yield) of the (2R) -3-benzyloxy-2- (N- (4-fluorobenzyl) amino) propanoic acid methyl ester, a compound of formula (O), as a colorless, transparent oil; NMR (CDC13) 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 way, The following compounds of formula (O) are prepared. 2R) -2- (N- (4-fluorobenzyl) amino) methoxy acid methyl ester; is (2S: (N-fluorobenzyl) amino) propanoic acid methyl ester; (2R) -2- (N- (4-fluorobenzyl) amino) -4-methylthiobutanoic acid methyl ester; (2R) -2 - (N- (4-fluorobenzyl) amino) -3-methoxypropanoic acid methyl ester; (2R) -2 - (N- (4-fluorobenzyl) amino) -3 ((2-hydroxyethyl) thio) propanoic acid methyl ester; and (2R) -2- (N- (4-fluorobenzyl) amino) -3-ethylbutanoic acid methyl ester. C. In a similar manner, the following compounds of formula (O) are prepared. (2S) -2 - (N- (4-fluorobenzyl) amino) -4-methylthiobutanoic acid methyl ester; (2S) -2 - (N- (4-fluorobenzyl) amino) -3-methoxypropanoic acid methyl ester; (2S) -2 (N- (4-fluorobenzyl) amino) -3 ((2-hydroxyethyl) thio) propanoic acid methyl ester; (2S) -2 - (N- (4-fluorobenzyl) amino) -3-methylbutanoic acid methyl ester; (2R) -2 - (N- (4-fluorobenzyl) amino) butanoic acid methyl ester; (2S) -2- (N-fluorobenzyl) amino) butanoic acid methyl ester; (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; (2R) -2 - (N- (4-chlorobenzyl) amino) -3-methoxypropanoic acid methyl ester; (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. In a similar manner, other compounds of formula (0) are prepared.

PREPARATION 8 Compounds of formula (Q) A. To a solution of N-t-butoxycarbonyl-D-alanine (5.6 g, 30 mmol, [a] D + 23 ° (c = 2, CH3C02H)) in anhydrous tetrahydrofuran (150 ml) under N2 at 0 ° C is added N-methylmorpholine (3.0 g, 30 mmol), followed by the addition of isobutyl chloroformate (3.7 ml, 30 mmol), resulting in the formation of a white solid. The resulting suspension is stirred at 0 ° C for 15 minutes and then at room temperature for 1 hour. A solution of the acid methyl ester is added to the mixture (2R) -3-benzyloxy-2- (N- (4-fluorobenzyl) -amino) clothingnoic (7.5 g, 24 mmoles, in 50 ml of anhydrous tetrahydrofuran) and the resulting mixture is stirred at room temperature. After 15 hours, the mixture is filtered through Celite (tetrahydrofuran). The filtrate is concentrated in vacuo to give a yellow liquid, which is dissolved in ethyl acetate, washed with water and then with brine. The organic phase is separated and then dried over MgSO4, filtered and concentrated in vacuo. Purification by flash column chromatography on silica gel afforded 7.3 g (63% yield) of (2R) -3-benzyloxy-2- (N- (4-fluorobenzyl) -N- (((1S)) methyl ester. ) -1- (t-butoxy-carbonylamino) ethyl) carbonyl) amino) propanoic, compound of formula (Q), as a clear oil; NMR (CDC13) 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. B. In a similar manner, the following compounds of formula (Q) are made: (2R) -2- (N- (4-fluorobenzyl) -N- (((S) -I- (t)) methyl ester -butoxycarbonylamino) ethyl) carbonyl) amino) propanoic; (2S) -2- (N- (4-fluorobenzyl) -N- (((1S) -1- (t-butoxycarbonylamino) ethyl) carbonyl) amino) propanoic acid methyl ester; (2R) -2- (N- (4-fluorobenzyl) -N- (((IR) -1 - (t-butoxycarbonylamino) ethyl) carbonyl) amino) propanoic acid methyl ester; (2S) -2- (N- (4-fluorobenzyl) -N- (((IR) -1- (t-butoxycarbonylamino) ethyl) carbonyl) amino) propanoic acid methyl ester; (2R) -2- (N- (4-fluorobenzyl) -N- (((S) -1- (t-butoxycarbonylamino) ethyl) carbonyl) amino) -4-methyl-iobutanoic 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- (((lSj -l -, (t-butoxycarbonylamino) ethyl) carbonyl) amino) -3 - ((2-hydroxyethyl) thio) methyl ester ) Propanoic acid (2R) -2- (N- (4-fluorobenzyl) -N- (((SS) -1- (t-butoxycarbonylamino) ethyl) carbonyl) amino) -3-methylbutanoic acid ester; (2R) -2- (N- (4-fluorobenzyl) -N- (((SS) -1 - (t-butoxycarbonylamino) -2- (ethoxycarbonyl) ethyl) -carbonyl) amino) propanoic acid methyl ester. In a similar manner, other compounds of formula (Q) are prepared.

PREPARATION 9 Compounds of formula (R) A. To a solution of the (2R) -3-benzyloxy-2 - (N- (4-f luorobenzyl) -N- (((S) -1- (t-butoxycarbonylamino) ethyl) carbonyl) amino acid methyl ester propane (2.0 g, 4 mmol) in CH2C12 (25 ml) is cooled to 0 ° C and trifluoroacetic acid (25 ml) is added dropwise over 2 hours. At the end of the addition, the ice bath is removed and the mixture is stirred at room temperature. After 2 hours, the mixture is concentrated in vacuo. The residual yellow oil is taken up in ethyl acetate and washed with a 1N aqueous solution of NaHCO 3. The organic layer is separated and then dried over MgSO4, filtered and concentrated in vacuo to provide 1.2 g (83% yield) of (2R, 5S) -1- (4-fluorobenzyl) -2- (benzyloxy) methyl. -5-methylpiperazine-3,6-dione, a compound of formula (R), as a clear 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, EM (LSIMS) 356.

B. In a similar manner, the following compounds of formula (R) are prepared: (2R, 5S) -1- (4-f luorobenzyl) -2,5-dimethylpiperazine-3,6-dione, - (2S, 5S ) -1- (4-f luorobenzyl) -2,5-dimethylpiperazine-3,6-dione, - (2R.5R) -1- (4-f luorobenzyl) -2,5-dimethylpiperazine-3,6-dione; (2S, 5R) -1- (4-f luorobenzyl) -2,5-dimethylpiperazine-3,6-dione; (2R, 5S) -1- (4-f luorobenzyl) -2- (2-methylthioethyl) -5-methylpiperazine-3,6-dione, - (2R, 5S) -1- (4-fluorobenzyl) -2- (methoxymethyl) -5-methylpiperazine-3,6-dione; (2R, 5S) -1- (4-f luorobenzyl) -2- ((2-hydroxyethyl) thiomethyl) -5-methylpiperazine-3,6-dio, - (2R, 5S) -1- (4-fluorobenzyl) -2- (1-Methylethyl) -5-methylpiperazine-3,6-dione, - y (2 R, 5 S) -1- (4-fluorobenzyl) -2-methyl-5- (ethoxycarbonyl) methylpiperazine-3, 6-dione. C. In a similar manner, other compounds of formula (R) are prepared: PREPARATION 10 Compounds of formula (S) A. A suspension of (2R, 5S) -1- (4-fluorobenzyl) -2- (hydroxy) methyl-5-methyl-piperazine-3,6-dione (2.0 g, 7.5 mmol) in anhydrous tetrahydrofuran (50 ml. ) under N2 at 0 ° C, lithium aluminum hydride (2.2 g, 60 mmol) is cautiously added. The resulting suspension is heated to reflux. After 15 hours, the mixture is cooled to room temperature and carefully suspended with water (2 ml), and then with a 1 N aqueous solution of KOH (6 ml). The resulting suspension is stirred at room temperature., For 30 minutes, and then filtered through Celite (ethyl acetate). The filtrate is concentrated in vacuo to provide 1.6 g (90% yield) of (2R, 5S) -1- (4-fluorobenzyl) _ 2- (hydroxy) methyl-5-methylpiperazine, compound of formula (S), as a white solid; NMR (CDC13) 7.3 (dd, 2), 7.0 (dd, 2), 4.2-4.0 (, 2), 3.5 (d, 1) 3.0 (m, 2), 2.7 (m, 2), 1.7 (m, 1), 1.0 (d, 3). B. In a similar manner, the following compounds of formula (S) are prepared: (2R, 5S) -1- (4-fluorobenzyl) -2,5-dimethylpiperazine; (2S, 5S) -1 - (4-fluorobenzyl) -2,5-dimethylpiperazine; (2R, 5R) -1 - (4-fluorobenzyl) -2,5-dimethylpiperazine; (2S, 5R) -1 - (4-fluorobenzyl) -2,5-dimethylpiperazine; (2R, 5S) -1- (4-f luorobenzyl) -2- (2-methylthioethyl) -5-methylpiperazine, - (2R, 5S) -1- (4-fluorobenzyl) -2- (metoxymethyl) -5-methylpiperazine; "(2R, 5S) -1- (4-f luorobenzyl) -2- ((2-hydroxyethyl) thiomethyl) -5-methylpiperazine; (2R, 5S) -1- (4-fluorobenzyl) -2- (1- methylethyl) -5-methylpiperazine, - and (2 R, 5 S) -1- (4-fluorobenzyl) -2-methyl-5 - (ethoxycarbonyl) methylpiperazine C. In a similar manner, other compounds of formula ( S): PREPARATION 11 Compounds of formula (W) A. To a solution of 3,4-trimethoxyphenol (2.8 g, 15 mmol) in DMF (60 ml) at 0 ° C is added potassium hexamethyldisilazide (32 ml, 16 mmol, 0.5 M solution in toluene). The resulting mixture is stirred at 0 ° C. After 20 minutes, 1- (chloro) acetyl-4- (t-butoxycarbonyl) -piperazine (4.6 g, 15 mmol, in 15 ml of DMF) is added and the mixture is stirred at room temperature.

After 2 hours, the mixture is poured into water and extracted with ethyl acetate. The organic layer is separated, dried over MgSO4, filtered and concentrated in vacuo to give 6.5 g (100% yield) of 1- ((3,4,5-trimethoxy-enoxy) methyl) carbonyl -4- (t) -butoxycarbonyl) piperazine, a compound of formula (W), as a yellow solid; NMR (CDC13) 7.2 (m, 2), 4.6 (s, 2), 3.8 (m, 9), 3.6 (m, 4), 3.4 (m, 4), 1.5 (s, 9) ppm. B. In a similar manner, the following compounds of formula (W) are prepared: 1- ((4-chlorofenyl) methyl) carbonyl-4- (t -butoxycarbonyl) piperazine; (3R) -1- ((4-chlorofenyl) methyl) carbonyl-3-methyl-4- (t-butoxycarbonyl) piperazine; (3S) -1- ((4-chloro-enyl) methyl) carbonyl-3-methyl-4- (t-butoxycarbonyl) piperazine; and 1- ((4-chlorophenyl) methyl) carbonyl-3- (2- ((((4-chlorofenoxy) methyl) carbonyl) oxy) ethyl) -4 - (t -butoxycarbonyl) piperazine. C. In a similar manner, other compounds of formula (W) are prepared.

PREPARATION 12 Compounds of formula (Y) A. To a solution of 4-chlorobenzylamine (0.50 g, 3.5 mmol) in toluene (15 ml) is added phosgene (7.3 ml, 14 mmol, 1.93 M solution in toluene). The resulting mixture is stirred at room temperature for 15 minutes, and then heated to reflux. After 2 hours at reflux, the mixture is cooled to room temperature and concentrated in vacuo to provide 0.70 g (100% yield) of 4-chlorobenzyl isocyanate, 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 (Y) are prepared.

EXAMPLE 1 Compounds of formula (la) 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 CH2C12 (30 ml) is added triethylamine (excess) and 4-chlorophenoxyacetyl chloride (1.5 g, 7.4 mmol, dropwise in 10 ml of CH2C12 solution). The resulting mixture is stirred at room temperature. After 20 minutes, analysis by analytical CCD shows that the complete consumption of the initial material has been carried out. The mixture is concentrated from the volatile fractions in vacuo and the residue is taken up in CH2C12. This is washed with a saturated aqueous solution of NaHCO 3, then with water, then with brine, dried over MgSO 4, filtered and concentrated in vacuo.

Purification by flash column chromatography on silica gel provides 2.16 g (79% yield) of (2R, 5R) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((hydroxy) methyl) piperazine, as a solid yellow foam: NMR (DMSO-de) 7.7 (broad s, 2), 7.3 (m, 4), 6.9 (d, 2), 5.0-4.2 ( m, 5), 4.0-3.2 (, 7), 1.2 (m, 3) ppm; MS (LSIMS) 406. B. In a similar manner, other compounds of formula (la) are prepared: 1- ((4-chlorophenoxy) methyl) carbonyl-4- (4-fluorobenzyl) -5-methylpiperazine trifluoroacetic acid salt; NMR (DMSO-dβ) 7.6 (m, 2), 7.3 (m, 4), 6.9 (m, 2), 5.0-3.8 (m, 6), 3.5-2.8 (m, 5), 1.4 (m, 3 ) ppm; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-ethylpiperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3-methylpiperazine, -4-benzyl-1- ((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 (CDC13) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.6 (s, 2), 4.4 (m, 1), 3.7 (m, 1), 3.4 (m, 2), 2.8 (m, 2), 2.0-1.7 (m, 5), 0.9 (m, 3) ppm; (2 S) -4- (4-f l or o b e n c i l) - 1 - ((4-chloro-enoxy) methyl) carbonyl-2- (2-methylpropyl) piperazine; (trans) -4- (4-f luorobenzyl) -1- ((4-chloro-enoxy) methyl) -carbonyl -2,5-dimethylpiperazine; NMR (CDCl 3) 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-f luorobenzyl) -1- ((4-chloro-enoxy) methyl) -carbonyl-2-benzylpiperazine, -4- (benzyl) -1- ((4-chlorofenoxi) met il) carbonyl-2-f-enylpiperazin-3-one; 4- (4-fluorobenzyl) -1- ((4-chloro-enoxy) methyl) carbonyl-2- (2-hydroxyethyl) piperazine; NMR (CDCl 3) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.7 (m, 3), 3.8-3.2 (m, 5), 2.8 (m, 2), 2.2 ( , 2), 2.0 (m, 2), 1.7 (m, 2) ppm; (cis) -4- (4-f luorobenzyl) -1- ((4-chloro-enoxy) methyl) -carbonyl-2,6-dimethyl-piperazine; NMR (DMS0-ds) 7.6 (m, 2), 7.3 (m,, 4), 6.9 (d, 2), 4.8 (m, 3), 4.4 (m, 3), 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, - (2R, 5S) -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; (2R) -4- (4-f luorobenzyl) -1- ((4-chloro-enoxy) methyl) -carbonyl-2- (2-methylpropyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chloro-enoxy) methyl) carbonyl-2- (butyl) piperazine; * (2R, 5S) -4- (4-f luorobenzyl) -1- ((4-chloro-enoxy) -methyl) carbonyl-2- (2-hydroxyethyl) -5-methylpiperazine; NMR (CDC13) 7. 3 (m, 4), 7.0 (t, 2), 6.9 (m, 2), 4.6 (, 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; (2S, 5R) -4- (4-f-luorobenzyl) -1- ((4-chloro-enoxy) -methyl) -carbonyl-2,5-dimethyl-piperazine; 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; hydrochloride salt of (2R, 5R), 4- (4-f luorobenzyl) -1- ((4-chlorofenoxyl) ethyl) carbonyl-2,5-dimethylpiperazine; NMR (DMSO-ds) 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; 4- (4-f luorobenzyl) -1- ((4-chloro-enoxy) methyl) carbonyl-2- (1,1-dimethylethyl) piperazine; (2S) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) -methyl) carbonyl-2- (2-methylpropyl) piperazine; (2R, 5S) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) -methyl) carbonyl-2- (2- (((4-chlorofenoxyl) -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-f luorobenzyl) -1- ((4-chloro-enoxy) methyl) carbonyl-3- (methoxycarbonyl) methylpiperazine; (2S) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) -methyl) carbonyl-2-propylpiperazine; (cis) -4- (4-f luorobenzyl) -1- ((4-chlorofenoxyl) methyl) carbonyl -2,3-dimethylpiperazine hydrochloride salt; NMR (DMSO-d6) 7.6 (m.2), 7.2 (m, 4), 6.9 (m, 2), 5.0-4.1 (m, 6). 3.5-2.9 (m, 4). 1.5-1.2 (m, 6) ppm; (2R) -4- (4-f luorobenzyl) -1- ((4-chlorofenoxi) et il) -carbonyl-2-benzylpiperazine, - (2R) -4- (4-f luorobenzyl) -1- (( 4-chloro-enoxy) methyl) -carbonyl-2-propyl-piperazine; 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), 2.7 (m, 2), 2.0-1.6 (m, 4), 1.2 (m, 2), 0.9 (m, 3) ppm; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3 - (ethoxycarbonyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxyethyl) piperazine; NMR (CDCl 3) 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; (2S) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) ethyl) -carbonyl-2-butylpiperazine; hydrochloride salt of (2R, 6R) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2,6-dimethylpiperazine; NMR (CDC13) 7.7 (broad s, 2), 7.2 (, 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; hydrochloride salt of (2S, 6S) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) -carbonyl-2,6-dimethylpiperazine; NMR (CDC13) 7.7 (s broad, 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) methyl) -carbonyl) spiro [cyclopropan-1,2 '-piperazine], - NMR (CDC13) 7.3 (m, 4), 7.0-6.8 ( m, 4), 4.6 (m, 4), 2.8 (m, 2), 2.2-1.6 (m, 4) ppm; 4- (4-f luorobenzyl) -1- ((4-chloro-enoxy) methyl) carbonyl-2- (trifluoromethyl) piperazine; hydrochloride salt of (2R, 5S) -4- (4-f luorobenzyl) -1- ((4-chlorofenoxi) methyl) -carbonyl-2-methyl-5- (2-methylthio) ethylpiperazine, - 4- (4 -f luorobenzyl) -1- ((4-chloro-enoxy) methyl) carbonyl-3 - (((((4-chlorofenoxi) methyl) carbonyl) oxy) methylpiperazine; (2S) -4- (4-f luorobenzyl) -1- ((4-chloro-enoxy) -methyl) -carbonyl-2-propyl-piperazine; NMR (CDCl 3) 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), 1.6-1.3 (m, 4) 0.9 (m, 3) ppm; (2R, 5S) -4- (4-fluorobenzyl) -1- ((-chlorophenoxy) methyl) -carbonyl-2-methyl-5- (1-methylethyl) piperazine; NMR (DMSO-ds) 7.6 (m, 2), 7.3 (m, 4), 6.9 (d, 2), 5.0-4.2 (m, 6), 3.5-3.1 (m, 4), 2.2 (m, 1 ), 1.2 (d, 3), 0.9 (d, 6) ppm; (2S) -4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) methyl) -carbonyl-2- (2-methylpropyl) piperazine; hydrochloride salt of (2R, 3R) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) -carbonyl-2,3-dimethylpiperazine, - NMR (DMS0-d6) 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; (3S) -4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) methyl) -carbonyl-3-butylpiperazine, - (3S) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) -carbonyl-3- (1-methylpropyl) piperazine, - (3R) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) ethyl) -carbonyl-3- (2-methylpropyl) iperazine; (3R) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) -carbonyl-3-butylpiperazine; (2R, 5R) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) -carbonyl-2-methyl-5- (benzyloxy) methyl-piperazine; NMR (CDC13) 7.3 (m, 8), 6.8 (m,, 5), 4.5 (m, 6), 3.6 (m, 5), 3.0 (m, 1), 2.7 (dd, 1), 2.3 (d) , 1), 1.2 (d, 3) ppm; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxyethyl) piperazine hydrochloride salt; hydrochloride salt of (2R) -4 - (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methylpiperazine, - (2R, 5S) -4- (4-fluorobenzyl) -1- ( (4-chlorophenoxy) methyl) -carbonyl-2-methyl-5- ((4-acetylpiperazin-1-yl) methyl) iperazine; 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- hydrochloride salt ((4-chlorophenoxy) methyl) carbonyl-2,5-dimethylpiperazine; (trans) -4- (4-Fluorobenzyl) -1- ((2-acetylamino-4-chlorophenoxy) ethyl) carbonyl-2,5-dimethylpiperazine; NMR (DMSO-d6) 9.5 (broad s, 1), 8.1 (broad s, 1), 7.7 (m, 2), 7.3 (m, 2), 7.0 (m, 2), 5.0 (, 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) ethyl) 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 (s broad, 1), 2.7 (dd, 1), 2.5 (c, 4), 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) methyl-piperazine, - 1- ((4-chloro-2- (acetylamino) phenoxy ) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; NMR (DMS0-ds) 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 (c, 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; (trans) -1- ((4-chloro-2- (propylcarbonylamino) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-ds) 9.5 (d, 1), 8.2 (s, 1), 7.8 (t, 2), 7.3 (t, 2), 7.0 (dt, 2), 6.8 (of, 1), 6.4 ( d, 1), 5.2-4.3 (m, 5), 3.9-2.8 (m, 5), 1.8 (d, 3), 1.3 (, 6) ppm; (trans) -1- ((4-chloro-2- (iso-propylcarbonylamino) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-ds) 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 (, 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-ds) 9.3 (s, 1), 8.2 (s, 1), 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) et il-carbonylamino) phenoxy) -methyl) carbonyl-2,5-dimethyl-4 - (4-fluorobenzyl) piperazine; NMR (DMSO-ds) 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 (c, 1), 3.7- 3.2 (m, 5), 2.9-2.6 (m, 6), 1.4-1.2 (m, 6) ppm; (trans) -1- ((4-chloro-2- (2- (ethoxycarbonyl) et-il-carbonylamino) phenoxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-ds) 9.6 (s.1), 8.1 (s, 1), 7.8 (t, 2), 7.3 (t, 2), 7.0 (m, 2), 5.2-4.2 (m, 5), 4.0 (c, 2), 3.8 (c, 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) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; NMR (DMSO-ds) 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 (, 1), 3.4-2.8 (m, 6), 1.4 (d, 1.5), 1.2 (d) , 1.5) ppm; (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 (m, 2), 7.0 (m, 3), 6.9 (m, 1), 4.7 (m, 3), 4.0 (s, 2), 3.8-3.1 (m, 5), 2.7 (dd, 1), 2.2 (d, 1), 1.3 (broad d, 3), 1.0 (broad s, 3) ppm; (trans) -1- ((4-chloro-2- (ethylcarbonylamino) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; NMR (CDC13) 9.4 (s, 1), 8.5 (s, 1), 7.3 (m, 2), 7.0 (m, 3), 6.8 (d, 1), 4.7 (, 3), 3.5 (m, 3), 3.1 (m, 2), 2.7 (dd, 1), 2.5 (c, 1), 2.2 (d, 1), 1. 3 (m, 6), 1.0 (m, 3) ppm; (trans) -1- ((4-chloro-2- (acetylaminomethyl) f-enoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; NMR (CDC13) 8-0 (broad s, 1), 7.3 (m, 3), 7.1 (dd, 1), 7.0 (m, 2), 6.8 (broad d, 1), 4.7 (m, 3), 4.4 (d, 1), 3.8-3.0 (, 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 (c, 1), 4.7 (m, 3), 4.2 (, 1), 3.7 (, 1), 3.5 (c, 2), 3.2 (m, 1), 3.1 (m, 1), 2.8 (d, 3), 2.7 (d, 3), 2.3 (broad d 1), 1.6 (d, 3), 1.3 (m, 3). 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- (1- (f-enylsulfonyl) (methyl) -aminoethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.6 (d, 2), 7.3 (m, 6), 6.9 (t, 2), 6.8 (t, 1), 5.6 (c, 1), 4.6 (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) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.2 (m, 4), 7.0 (t, 2), 6.8 (m, 1), 6.0 (, 1), 5.4 (c, 1), 4.6 (m, 3), 4.2 (m, 1), 3.5 (c, 2), 3.2 (m, 1), 3.0 (m, 1), 2.6 (m, 4), 2.2 ( m, 3), 1.3 (m, 6), 0.9 (, 3) ppm; (trans) -1- (2- (4-chlorophenyl) -3- (methylsulfonylamino) -propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (t, 4), 7.2 (broad d 2), 7.0 (t, 2), 5.0 (broad s, 1), 4.6 (s broad, 1), 4.0 (m, 1), 3.4 (m, 5), 3.0 (m, 2), 2.8 (s, 3), 2.6 (m, 2), 2.2 (broad 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 (, 4), 7.2 (broad d 2), 7.0 (t, 2), 5.2 (m, 1), 4.6 (s broad, 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-chloro-enyl) -2- (methylsulphonylamino) -ethyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) iperazine; NMR (CDCI3) 7.3 (m, 5), 7.0 (t, 2), 6.6 (m, 1), 4.9 (c, 1), 4.6 (m, 0.5), 4.2 (broad d 0.5), 3.8 (m, 1 ), 3.5 (m, 1), 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-chlorofenyl) -2- (acetylamino) ethyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) 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, 4), 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 (DMS0-ds) 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) iperazine; NMR (DMSO-d6) 11.0 (m, 1), 7.9 (t, 2), 7.7. (t, 1), 7.6, (S, 1), 7.5 (d, 1), 7.3 (m, 4), 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 (m, 2), 2.8 (m, 1), 1.4 (dd, 3), 1.2 (dd, 3) ppm; (trans) -1- ((4-chloro-2- ((4- ((2,3-, 4-trifluorophenyl) -aminocarbonyl) iperazin-1-yl) methyl) phenoxy) methyl) carbonyl -2,5-dimethyl -4- (4-fluorobenzyl) piperazine: NMR (DMSO-ds) 11.0 (m, 1), 9.0 (s, 1), 7.9 (t, 2), 7.7. (, 1), 7.6 (s, 1), 7.5 (m, 1), 7.2 (m, 4), 5.4 (m, 1), 5.0 (m, 2), 4.4 (m, 6), 3.4 (m , 8), 3.1 (m, 2). 2.8 (m, 1), 1.4 (, 3), 1.2 (m, 3) ppm, - (trans) -1- ((4-chloro-2- ((4- ((2-f luorofenyl) -aminocarbonyl ) piperazin-1-yl) methyl) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-ds) 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, l), 1.4 (dd, 3), 1.2 (dd, 3) ppm; (trans) -1- ((4-chloro-2- ((N 1 - (2,6-dif luorofenyl) -ureido) f enoxi) met il) carboni l-2, 5-met il-4 (4 - fluorobenzyl) piperazine; NMR (CDC13) 9.6 (broad 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 (s broad, 0.5), 3.8 (s broad, 0.5), 3.5 (c, 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-f luorobenzyl) iperazine; NMR (CDC13) 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 (c, 2), 3.2 (m, 1), 3.0 (m, 1 ), 2.7 (dd, 1), 2.2 (dd, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- (cyclopropylcarbonylamino) -phenoxy) ) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) iperazine; NMR (CDCl 3) 9.7 (broad s, 1), 8.4 (s, 1), 7.3 (m, 2), 7.0 (m, 3), 6. 8 (d, 1), 4.7 (m, 3), 3.7 (m, 1), 3.5 (c, 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 (, 2) ppm; (trans) -1- ((4-chloro-2- (cyclopentylcarbonylamino) -phenoxy) methyl) carbonyl-2, 5 -dimethyl-4- (4-fluorobenzyl) iperazine NMR, (CDCl 3) 9.3 (broad 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 (c, 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-ds) 10.4 (broad s, 1), 9.7 (broad d, 1), 8.2 (broad s, 1), 7.9 (s, 1), 7.7 (m, 2). 7.3 (m, 3), 7.2 (s, 2), 6.7 (d, 1), 5.3 (d wide 1), 5.0 (m, 2), 4.7 (, 0.5), 4.5 (, 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), 3.7 (m, 1), 3.5 (c, 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-chloro-enyl) -2- ((ethoxycarbonylmethyl-carbonylamino) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 8.6 (m 1), 7.2 (6), 7.0 (t, 2), 5.4 (m, 1), 4.2 (c, 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) piperazine; NMR (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 (m, 1), 3.0 (m, 3), 2. 6 (, 1), 2.2 (m, l), 1.1 (m, 9), 0.9 (dd, 1.5), 0.8 (dd, 1.5) ppm; (trans) -1- (2- (4-chlorofenyl) -2- (N 1 - (2-chloroethyl) -ureido) ethyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; NMR (CDC1377.3 (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, 4), 2.6 (m, 1), 2.2 (m, l), 1.1 (m, 3), 0.9 (dd, 1.5) , O.8 (dd, 1.5) ppm; (trans) -1- (2- (4-chlorophenyl) -2- ((2-nitrophenyl) -carbonylamino) ethyl) carbonyl-2,5-dimethyl-4 - (4-f-luorobenzyl) piperazine; NMR (CDC13) 8.1 (d, 1), 7.7 (c, 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, l), 1.2 (m, 3), 0.9 (m , 3) ppm; (trans) -1- (2- (4-chloro-enyl) -2- ((4-methoxyphenylmethyl) -carbonylamino) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (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-chlorofenyl) -2 - ((2,4-dinitrophenyl) sulf onylamino) ethyl) carbonyl -2,5-dimethyl-4 (4-fluorobenzyl) piperazine; NMR (CDC13) 8.6 (s, 1), 8.2 (d, 1), 7.8 (m, 1), 7.3 (m, 4), 7.0 (t, 2), 6.9 (t.2), 5.0 (m, 1), 4.6 (m, 0.5), 4.1 (m, 0.5), 3.5 (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- (cyclopropyl-carbonylamino) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 6), 7.0 (t, 2), 5.2 (m, 1), 4.6 (, 0.5), 4.2 (m, 0. 5), 3.5 (m, 2), 3.4 (m , 1), 3.0 (m, 3), 2.6 (m, 2), 2.2 (m, 1), 1. 5 (m, 1), 1. 2 (m, 3), 0.9 (m, 3.5), 0.7 (m, 3.5) ppm, - (t rans) -l- (2 - (4-chloro f in il) -2- ((2-cyclopropylethyl) carbonylamino) ethyl) carbonyl-2, 5-dimethyl-4 - (4-f luorobenzyl) 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, 4), 2.6 (m, 1), 2.2 (m, 2), 1.6 (, 10), 1. 2 (m, 3), 1.1 (m, 2), 0.8 (m, 3) ppm; (trans) -1- (2- (4-chloro-enyl) -3- ((2-methyl-ylpropyl) -carbonylamino) -propyl) -carbonyl-2,5-dimethyl-4 (4-f-luorobenzyl) -piperazine; NMR (CDC13) 7.3 (d, 4), 7.2 (d, 2), 7.0 (t, 2), 6.0 (broad 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, 4), 1.2 (m, 3), 0.9 (m, 9) ppm; (trans) -1- (2- (4-chlorofenyl) -3- (cyclopentylcarbonyl-amino) propyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; NMR (CDC13) 7.3 (d, 4), 7.2 (d, 2), 7.0 (t, 2), 6.0 (broad 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 (, 3), 2.4 (m, 1), 2.2 (d.1), 1.6 (m, 8) , 1.1. (m, 4), 0.9 (m, 4) ppm; (trans) -1- (2 - (4-chlorofenyl) -3- (N 1 - (t-butyl) ureido) propyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (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, 4), 3.2 (m, 1), 3. 0 (m, 1), 2.6 (, 2), 2.2 (d, 1), 1. 3 (s, 9), 1. 2 (m, 3 ), 0.9 (m, 3) ppm; (trans) -1- (2- (4-chloro-phenyl) -3- (N 1 - (ethyl) ureido) -propyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) -piperazine, NMR ( CDC13) 7.3 (d, 4), 7.2 (d, 2), 7.0 (t.2), 5.1 (m, 1), 4.9 (m, 1), 4.6 (m, 0. 5), 4.2 (, 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 1 - (3-chloropropyl) ureido) propyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine, NMR (CDC13) 7.3 (d, 4), 7.2 (d.2), 7.0 (t, 2), 5.6 (s broad, 1), 5.9 (s, 1), 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-f luorobenzyl) piperazine; NMR (CDC13) 7.3 (d, 4), 7.2 (d, 2), 7.0. (t, 2), 5.8 (broad 1), 4.6 (m, 0. 5), 4.2 (m, 0. 5), 3.6 (, 6), 3.4 (m, 4), 3.3 (t, 4), 3. 0 (m, 2), 2.6 (m, 3), 2.2 (m, 1) 1.2 (, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- ((N '- (methoxycarbonyl-methylcarbonyl) -N' - (methyl) glycinamide) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4- f luorobenzyl) piperazine; NMR (CDC13) 9.6 (broad 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, 4), 3.5 (m, 2), 3.1 (m, 4), 2.7 (dd, 1), 2.2 (d, 1) , 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- ((N1 - (2-methyl-oxo-carbonyl-ethyl) carbonyl-N '- (methyl) glycinamide) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; NMR (CDC13) 9.6 (s broad, 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 (c, 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-f luorobenzyl) piperazine; NMR (CDC13) 9.6 (s broad, 1), 8.4 (d, 1), 7.3 (dd, 2), 7.2 (t, 1), 7.0 (m, 6), 6.8 (d, 1), . 4 (t, 1), 4.6 (m, 3), 4.4 (d, 2), 4.3 (s, 2), 3.8 (m, 1), 3.5 (c, 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 1 - (3-trifluoromet-il-4 -f luorofenyl) carbonyl-N '- (methyl) gyl cinnamido) phenoxy) methyl) carbonyl-2 , 5-dimethyl-4- (4-f luorobenzyl) piperazine; NMR (CDC13) 9.8 (broad s, 1), 8.4 (d, 1), 8.1 (broad s, 1), 7.6 (m, 2), 7.3 (dd, 2), 7.0 (m, 4), 6.8 (d, 1), 4.7 (m, 3), 4.3 (t, 2), 3.7 (m, 1), 3.6 (c, 2), 3.2 ( s, 3), 3. l (m, 2), 2.7 (m, 1), 2.2 (d, 1), 1.3 (m, 3), 0.9 (, 3) ppm; (trans) - 1 - (( 4-chloro-2 - ((N '- (4-methylbenzyl) aminocarbonyl-N' - (methyl) gilcinamido) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) ) 9.6 (s broad, 1), 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), 3.6 (c, 2), 3.1 (m, 5), 2.7 (m, 1), 2.3 (s, 3), 2.2 (d, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- ((N1 (3-chlorofenyl) carbonyl-N '- (methyl) glycinamide) phenoxy) I il) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 9.9 (broad 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 (s broad, 2), 4.1 (m, 1), 3.6 (m, 1), 3.5 (c, 2), 3.2 (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-2- ((N1- (4-fluorobenzyl) -aminocarbonyl-N '- (methyl) glycinamide) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4 -f luorobenzyl) piperazine; NMR (CDC13) 9.7 (broad 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), 4.2 (m, 2), 3.6 (m, 1), 3.5 (c, 2), 3.1 (, 5), 2.7 (m, 1) , 2.2 (d, 1), 1.3 (m, 3), 0.9 (, 3) ppm; (trans) -1- ((4-chloro-2- (N '- (methoxymethylcarbonyl) -glycinamido) phenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 10.1 (broad 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 (c, 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) -glycinamido) phenoxymethyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 9.9 (broad s, 1), - (m, 2), 7.3 (m, 3), 7 0 (m, 6.8 (d, 1), 4.7 (m, 3), 4.4 (m,, 3.6 (m, 1), 3.5 (c, 2), 3.1 (m, 2), 2.7 (dd, 1), 2.2 (d, 1), 1.3 (m, 6), 0.9 (m, 3) ppm; (t r a n s) - 1 - ((4-c l o r o - 2 - (N 1 - (2-iodophenylcarbonyl) glycinamide) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 10.4 (broad 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 (c, 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-difluorofenylcarbonyl) -glycinamido) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) -piperazine; NMR (CDC13) 10.3 (broad s, 1), 8.4 (d, 1), 7.8 (t, 1), 7.5 (quin, 1), 7.3 (m, 3), 7.2 (m, 1), 7.0 (t, 3), 6.8 (d, 1), 4.7 (m, 3), 4.4 (d, 2), 3.6 (m, 1), 3.5 (c, 2), 3. 1 (m, 2), 2.7 (dd, 1), 2.2 (d ,.l), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- (N * - ((4-f-enoxyphenyl) -aminocarbonyl) glycinamide) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 9.9 (broad s, 1), 8.3 (broad s, 1), 7.3 (, 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 (c, .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 '- (2,4-difluorylcarbonyl) -glycinamido) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) ) piperazine; NMR (CDC13) 10.3 (broad s, 1), 8.4 (d, 1), 8.1 (c, 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 (m, 1), 3.5 (c, 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- ((2-iodoxycarbonyl) -aminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f-luorobenzyl) piperazine; NMR (CDC13) 8.0 (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 (c, 2), 3.1 (m, 2), 2.6 (m, 1), 2.2 (m, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- ((ethoxycarbonylmethylcarbonyl) -aminomethyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 8.4 (broad 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 (c, 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 1 - (3-chloropropyl) ureidomethyl) -phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; NMR (CDC13) 7.3 (, 3), 7.2 (dd, 1), 7.0 (m, 2), 6.8 (d, 1), 4.8 (, 4), 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 (who, 2), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- (N 1 - (2-f luoro-6-trif luoromethyl-f-enyl) ureidomethyl) phenoxy) methyl) carbonyl -2,5-dimethyl -4- (4- fluorobenzyl) piperazine; NMR (CDC13) 8.2 (, 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 (c, 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-f luorofenyl) carbonyl-aminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 8.6 (m, 1), 7.8 (t, 2), 7.3 (m, 4), 7.2 (dd, 1), 7.1 (dt, 1), 7.0 (t, 2), 6.8 (d, 1), 4.8 (, 3), 4.6 (d, 2), 3.8 (m, 1), 3.5 (c, 2), 3.1 (m, 2), 2.6 (m, 1), 2.2 (d, 1) , 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-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 (, 3), 4.4 (d, 2), 4.1 (c, 2), 3.6 (m, 2), 3.4 (m, 3), 3.2 (m, 1), 3.1 (m, 2), 2. 7 (m, 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 (c, 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- (N1 - (2- (phenyl) cyclopropyl) -ureidomethyl) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 8), 7.0 (m, 3), 6.8 (d, 1), 4.9 (s, 1), 4.6 (d, 2), 4.4 (, 2), 3.8 (m, 1), 3.5 (c, 2), 3.2 (m, 1), 3.0 (, 1), 2.7 (m, 2), 2.2 (, 1), 2.0 (m, 1), 1. 3 (m, 5), 0.9 (m, 3) ppm. ' C. In a similar manner, the following compounds of formula (Ib) are prepared: 1- (2 - (4-chlorophenyl) ethenyl) carbonyl-4- (4-fluorobenzyl) piperazine, - 1 - (2 - (4 - chlorophenyl) ethyl) carbonyl -4 - (4-f luorobenzyl) piperazine; 1 - (1 - (t-butoxy-a rb on i l) ami-2 - (4-chloro-enyl) -ethyl) -carbonyl-4- (benzyl) -piperazine; 1- (3 - (t-butoxycarbonyl) amino) - 2- (4-chloro-enyl) -propyl) -carbonyl-4- (4-f-luorobenzyl) -perazine; NMR (CDC13) 7.2 (, 8), 4.8 (m, 1), 3.6-3.3 (m, 8), 2.6 (m, 2), 2.3 (m, 3), 2.1 (m, 1), 1.4 (s) 9) ppm; 1- (2 - (3,4,5-trimethoxyphenyl) ethenyl) carbonyl-4- (4-fluorobenzyl) iperazine; NMR (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; 1- (2 - (3, 4, 5 -trimetho ifyl) ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((acetyl) amino) (4-chlorofenyl) methyl) carbonyl-4- (4-f luorobenzyl) piperazine hydrochloride salt. D. "In a similar manner, other compounds of formulas (la), (Ib), (le) and (Id) are made.

EXAMPLE 2 Compounds of formula (la) A. To a solution of (2R, 5S) -1- (chloro) acetyl-4- (4-fluorobenzyl) -2,5-dimethylpiperazine (0.29 g, 1 .mol) in anhydrous DMF (5 mL) is added 4 -hydroxy-3-methoxyphenylacetonitrile (0.20 g, 1.2 mmol) and potassium carbonate (0.28 g, 2 mmol, pulverized). The resulting mixture is stirred at 50 ° C. After 15 hours, analysis by analytical CLAP (CLAP in a C18 Vydac column with 20-70% acetonitrile in a water gradient, with 0.1% trifluoroacetic acid) shows that the complete consumption of the initial material has been carried out . The mixture is poured into water and extracted with three portions of ethyl acetate. The combined organic extracts are washed sequentially with a 0.5 N aqueous solution of KOH, water and then brine. They are then dried over MgSO4, filtered and concentrated in vacuo to give a yellow oil. This is dissolved in ethyl acetate and treated with a solution of HCl in anhydrous ether. Filtration of the resulting solid gives 0.38 g (85% yield) of the hydrochloric acid salt of (2R, 5S) -1- ((4- (cyano) methyl-2-methoxy-3-enoxy) ethyl) carbonyl -4- (4 - chlorobenzyl) -2,5-dimethylpiperazine, as a white solid: NMR (DMS0-d6) 11.5 (broad s, 1), 7.6 (m, 4), 6.9 (m, 3), 4.8 (broad s, 2), 4.4 (s broad, 3). 4.0 (m, 1), 3.9 (s, 2), 3.8 (s, 3), 3.6 (m, 1), 3.3 (, 2), 3.2-2.9"(m, 3) ppm B. In a way similarly, other compounds of formula (la) are prepared: (trans) -1- ((4-f luoro-3-chlorofenoxi) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; NMR (DMSO-ds) 10.4 (broad 1), 7.7 (m, 2), 7.2 (m, 4), 6.9 (broad 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-acetylamino enoxi Jraethyl) carbonyl- 4- (4-f luorobenzyl) piperazine; NMR (DMSO-ds) 10.6 (broad s, 1), 9.4 (s, 1), 8.0 (d, 1), 7.8 (s broad, 2), 7.2 (t, 2), 6.9 (m, 3), 5.0 (m, 3), 4.3 (m, 3), 3.8 (c, 1), 3.6 (s broad, 1), 3.4 (m, 1), 2.8 (, 1), 2.1 (s, 3), 1.3 ( dd, 3), 1.2 (d, 3) ppm, -1- ((3, 4, 5-trimethoxyp enoxi) methyl) carbonyl-2- (methoxycarbonyl) methyl-4- (4-f luorobenzyl) piperazine; 1- ((3, 4, 5-trimethoxyphenoxy) methyl) carbonyl-2- (ethoxycarbonyl) -4- (4-f luorobenzyl) 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 (, 4), 3.8 (, 9), 3.5 (s, 2), 2.6 (d, 2), 2.2 (dd, 2), 1.3 (, 6) ppm; l- ((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 (, 1), 3.8 (s, 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-f luorobenzyl) 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) m t il) 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), 2.7 (m, 1), 2.5 (m, 1), 2.1 (m, 1), 1.1 (m, 3) ppm; (2S) -1- ((4-chloro-enoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) iperazine; (2R) -1- ((4-chloro-enoxy) methyl) carbonyl-2-methyl-4- (4-f luorobenzyl) 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-chlorophenoxy) methyl) carbonyl-3- (((4-chlorophenyl) amino) carbonyl) methyl -1- (benzyl) iperazin-2-one; 1- ((phenoxy) methyl) carbonyl-2-ethyl-4- (4-f-luorobenzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-2-hydroxymethyl-4- (4-f luorobenzyl) 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, - (2S, 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 (, 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, 4), 0.9 (m, 3) ppm; (2R, 5S) -1- ((4-chloro-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 (CDC13) 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 (m, 4), 3.0 (m, 1), 2.7 (dd, 1), 2.2 (d, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; hydrochloride salt of (2S, 5R) -1- ((4-bromo-3,5-dimethoxyphenoxy) methyl) -carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) -piperazine; NMR (DMSO-d6) 10.7 (d, 1), 7.8 (m, 2), 7.3 (m, 2), 6.3 (s, 2), 4.9 (, 2), 4.3 (m, 2). 4.0-2.8 (m, 12), 1.4-1.2 (m, 6) ppm; (2S, 5R) -1- ((4-nitro-3-f ormilf enoxi) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; NMR (CDC13) 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-f luorobenzyl) piperazine; NMR (CDC13) 9.2 (broad 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 (broad s, 3) ppm; (2R, 5S) -l- ((4-chloro-2- (aminocarbonyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; NMR (CDC13) 9.2 (broad s, 1), 8.2 (s, 1), 7.4 (m, 4). 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 (broad s, 3) ppm; (2R, 5S) -l- ((4-chloro-enoxy) methyl) carbonyl-2-methyl-5- ((amino) carbonyloxy) methyl-4- (4-f-luorobenzyl) piperazine; (trans) -1- ((4-chloro-3-nitro-enoxy) methyl) carbonyl-2, 5-dimethyl-4 - (4-fluorobenzyl) piperazin hydrochloride salt; NMR (DMS0-ds) 11 (broad d 1), 7.9 (broad s, 1), 7.6 (m, 2), 7.3 (m, 4), 5.2 (d, 1), 5.0 (m, 2), 4.3 (m, 4), 4.0 (m, 1), 3.6 (m, 2), 1.3 (m, 6) ppm; hydrochloride salt of (trans) -1- ((4-chloro-2- (hydroxymethyl) phenoxy) methyl) -carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-ds) 10.9 (broad 1), 7.9 (broad s, 2), 7.6 (m, 1), 7.3 (m, 4), 5.0 (m, 2), 4.5 (s, 2), 4.3 (m, 2), 3.7-3.3 (m, 6), 1.3 (, 6) ppm; hydrochloride salt of (trans) -1- ((4-chloro-2-aminofenoxyl) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-dg) 7.7 (broad s, 3), 7.3 (m, ), 5.2 (d, 1), 5.0 (m, 2), 4.7-4.2 (m, 4), 3.9-3.4 (m, 3), 1.3 (m, 6) ppm; (trans) -1- ((2- (aminocarbanyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 9.1 (broad s, 1), 8.2 (d, 1), 7.4 (dd, 1), 7.3 (s broad, 2), 7.1 (t, 1), 7.0 (m.2), 6.9 ( d, 1), 5.8 (s broad, 1), 4.7 (m, 2), 4.2 (m, 1), 3.7-3.4 (, 3), 3.0 (s broad, 1), 2.7 (s broad, 1) , 2.3 (d, 1), 1.3 (m, 3), 1.0 (, 3) ppm; (trans) -1- ((4-Chloro-2-amino-5-nitro-enoxy) (methyl) -carbonyl-2,5-dimethyl-4 - (4-fluorobenzyl) piperazine dihydrochloride; NMR (CDC13) 10.9 ( d broad 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 (broad 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-f luorobenzyl) piperazine; NMR (CDC13) 10.9 (broad 1), 10.4 (s, 1), 7.8 (s, 1), 7.5 (dd, 1), 7.3 (dd, 2), 7.0 (, 3), 4.8 (m, 3 ), 4.1 (m, 1), 3.5 (m, 3), 3.0 (s broad, 1), 2.7 (dd, 1), 2.5 (d, 1), 1.3 (m, 3), 0.9 (m, 3 ) ppm; (trans) -1- ((2-methylphonoxy) methyl) carbonyl-2, 5-dimethyl-4 - (4-fluorobenzyl) piperazine hydrochloride salt; NMR (DMSO-ds) 1 1.0 (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; hydrochloride salt of (trans) -l - ((2- (hydroxymethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; NMR (DMSO-ds) 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: hydrochloride salt of (trans) -1- ((3-chloro-5-methoxy-enoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) -piperazine; NMR (DMS0-ds) 10.8 (d, 1), 7.8 (m, 2), 7.3 (t, 2), 6.6 (s, 2), 6.5 (s broad, 1), 5.0-3.2 (m, 12), 2.8 (m, 1), 1.4-1.2 (m, 6) ppm; (trans) -1- ((2-methoxy-5-nitro-enoxy) methyl) carbonyl-2, 5-dimethyl-4 - (4-fluorobenzyl) piperazine hydrochloride salt; NMR (DMSO-ds) 11.1 (d, 1), 7.9 (m, 2 '7.7 (s broad, 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-fluorobenzyl) piperazine; NMR (DMSO-d6) 11 d, 1), 7.7 (m, 2), 7.3 (m, 4), 6, 3), 4.9 (m, 3), 4.3 (m, 3), 4.0-2.8 (m , 5), 1.4 (d, 1.5). (trans) -1- ((4-chlorophenylamino) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) .7.4 (dd, 2), 7.1 (m, 4), 6.6 (d, 2). 5.8 (t, 1), 4.5 (s broad, 0.5), 4.0 (broad m, 1.5), 3.8 (broad m, 1), 3.8-3.3 (m, 3), 3.0 (m, 2), 2.6 (m , 1), 2.2 (d, 1), 1.1 (broad d, 3), 0.9 (broad d, 3) ppm; (trans) -1- ((4-chloro-3-nitrophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-ds) 11 (broad d 1), 7. 7 (m, 4), 7.3 (m, 3), 5.0 (c, 2), 4.7 (m, 0.5), 4.4 (m, 2.5), 3. 8 (m, 0.5), 3.6-2.9 (m, 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 (broad d 1), 7.9-6.8 (, 7), 5.1-2.8 (m, 1 0), 2.2 (s, 3), 1.3 (m, 6) ppm; (trans) -1- ((4-chloro-2- (diethylamino) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 2), 7.0 (t, 2), 6.8 (m, 3), 4.8 (broad s, 3). 4.1 (s broad, 1), 3.5 (c, 3), 3.2 (c, 4), 3.0 (s broad, 1), 2.7 (dd, 1), 2.2 (d, 1), 1.3 (s broad, 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 (, 5), 4.9 (m, 0.5), 4.6 (s broad, 2), 4.2 (m, 0.5), 3.6- 3.2 (m, 3), 3.0 (broad 1), 2.7 (broad 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-dg) 10.8 (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; (2R, 5S) -1- ((4-chloro-3- (hydroxymethyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; NMR (CDC13) 7.3 (, 4), 7.0-6.7 (m, 3), 4.7 (m, 4), 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 (m, 1), 1.2 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- (ureidomethyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; NMR (DMSO-ds) 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 (broad d, 3), 0. 9 (broad d 3) ppm; 1- ((4-chloro-2-aminophenoxy) methyl) carbonyl -2-methyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-d6) 11.2 (broad 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 (m, 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 (broad 1), 7.8 (broad 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; (2S) -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 (c, 3), 5.0 (s, 2), 4.6 (dt, 2), 4.4 (d, 0.5), 3.7 (s broad, 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; (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 (c, 3), 5.0 (s, 2), 4.6 (dt, 2), 4.4 (d, 0. 5), 3.7 (s broad, 0. 5), 3.4 (, 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-ds) 10.8 (s broad, 1), 8.2 (s broad, 2), 7.8 (s broad, 2), 7.7 (s broad, 1), 7.3 (m, 2), 6.8 (s broad, 2), 5.2-4.3 (m, 5), 3.9-3.1 (m, ), 2.8 (t, 1), 1.5-1. 1 (m, 6) ppm; (2R, 5S) -1- ((4-chloro-2- (ureido) f enoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; NMR (CDC13) 9-0 (s, 1), 8.3 (s, 1), 7.3 (t, 1), 7.0 (t, 3), 6.8 (, 3), 5.0 (s, 2), 4.6 (m , 2), 4.2 (d, 0.5), 3.7-3.4 (m, 2.5), 3.2 (m, 2), 2.7 (d, 1), 2.5 (m, 1), 2.2 (d, 1), 1.3 ( d broad 3), 1.0 (broad 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), 7.0 (m, 3), 4.8 (m, 3), 4.1 (broad d 1), 3.5 (m, 3), 3.0 (m, 1), 2.7 (dd, 1), 2.3 (d, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; 1- ((4-chloro-2-methoxycarbonylphenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-ds) 11.0 (broad 1), 7.7 (m, 3), 7.6 (dd, 1), 7.3 (t, 2), 7.0 (d, 1), 5.0 (of, 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-methoxycarbonylphenoxy) -methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.9 (broad 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, 4), 3.5 (m, 2), 2.8 (m, 2), 1.6 (m, 3), 1.3 (m, 3) ppm; 1- ((4-chloro-2-aminocarbonylphenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 9.6 (broad 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 (, 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; 1- ((4-chloro-2- (aminocarbonyl) phenylamino) methyl) -carbonyl-2-methyl-4- (4-f luorobenzyl) piperazine; NMR (DMSO-d6) 11.2 (broad s, 1), 7.9 (broad s, 1), 7.7 (m, 3), 7.2 (m, 2), 6.6 (d, 1), 4.8 (broad 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 (s broad , 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) iperazine; NMR (DMSO-ds) 1 1.0 (broad 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 (m, 3), 1.5 (d, 1.5), 1. 3 (d, 1.5) ppm; (2R, 5S) -1- ((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), 4.1 (m, 1), 3.5 (m, 3), 3.1 (s broad, 1), 2.7 (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 (s broad, 2), 4.7 (m , 1), 4.2 (m, 1), 3.4 (, 3), 3.1 (m, 1), 2.8 (d wide 1), 2.6 (d wide 1), 2.1 (m, 1), 2.0 (dd, 1 ), 1.3 (m, 3) ppm; (trans) -1- ((4-chloro-2-cyanophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.5 (dd, 1), 7.3 (m, 2), 7.0 (m, 4), 4.8 (m, 3), 4.1 (m, 1), 3.5 (, 3), 3.0 (m, 1 ), 2.7 (, 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 (DMS0-d6) 10.8 (broad d, 1), 7.8 (s, 2), 7.5 (m, 2), 7.3 (m, 3), 7.2 (m, 1), 5.3 (m, 1), 5. Oís, 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) iperazine; NMR (DMSO-ds) 1 1.0 (broad s, 1), 9.4 (s, 1), 8.0 (d, 1), 7.6 (d, 2), 7.3 (t, 2), 7.0 (m, 3), 4.9 (c, 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) 1 1.0 (broad 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-ds) 10.5 (broad 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-ds) 11.0 (broad m, 1), 7.8 (S, 2), 7.2 (, 5), 5.3 (m, 1), 5.0 (m, 2), 4.3 (m, 3). 4.0 (m, 1), 3.5 (, 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-ds) 11.0 (broad d, 1), 10.0 (s, 1), 7.9 (S, 2), 7.5 (m, 2), 7.3 (m, 3), 6.9 (, 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 (CDC13) 7.5 (s, 1), 7.3 (m, 3), 7.0 (t, 2), 6.8 (d, 1), 4.7 (m, 3). 4.2 (broad d, 1), 3.6 (m, 1), 3.5 (c, 2), 3.0 (broad s, 1), 2.7 (m, 4), 2.2 (m, 4), 1. 3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((2-methoxycarbonylphenoxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 12.1 (s, 1), 7.8 (, 3), 7.3 (s broad, 1), 7.0 (broad s, 4), 4.8 (m, 2), 4.3 (m, 3), 3.9 (, 5), 3.6 (m, 1), 2.8 (, 1), 2.4 (, 1), 1.6 (m, 3), 1. 3 (m 3) ppm; (trans) -1- ((3-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; NMR (DMSO-ds) 10.8 (broad 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) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; NMR (DMSO-d5) 9.7 (broad d, 1), 8.6 (s, 1), 8.5 (s, 1), 8.1 (1), 7.8 (s, 1), 7.6 (s broad, 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) ) ethyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMS0-, ds) 11.2 (broad 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-d6) 10.5 (broad d, 1), 7.7 (m, 4), 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 (c, 1), 3.6 (d wide 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-ds) 11.2 (broad 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 (, 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 (DMSO-d6) 11.2 (broad d, 1), 7.9 (t, 2). 7.7 (d, 1), 7.6 (s, 1), 7.3 (t, 2), 6.7 (d, 1), 5.0 (m, 3), 4.7 (m, 1), 4.3 (, 2), 4.0 ( c, 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-ds) 11.3 (m, 1), 7.9 (broad s, 2), 7.8 (broad m, 1), 7.3 (m, 4), 7.0 (t, 1), 5.3 (m, 1), 5.0 (, 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-dβ) 10.5 (broad d 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-ds) 11.2 (broad s, 1), 7.9 (broad s, 2), 7.3 (m, 3), 7.1 (s, 2), 5.2 (d, 1), 4.9 (s, 2), 4.3 (m, 3), 3.9-3.4 (m, 9), 2.8 (m, 1), 1.4-1.2 (m, "6) ppm; (trans) -1- ((5-methoxy-2-acetylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) iperazine; NMR (DMSO-ds) 11.2 (broad d, 1), 7.9 (dd, 2), 7.6 (m, 1), 7.3 (t, 2), 6.6 (c, 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) aminoc rbonyl) -phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; NMR (DMSO-dg) 10.8 (broad d, 1), 9.1 (broad s, 1), 7.9 (d, 1), 7.8 (broad 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), 1.4-1.2 (m 6) ppm; (trans) -1- ((2- ((2-Hydroxyethoxy) carbonyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-ds) 10.0 (s broad), 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 (c, 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) iperazine; NMR (DMSO-d6) 10.5 (broad 1), 7.8 (t, 2), 7.3 (t, 2), 6.9 (m, 4), 4.8 (, 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-ds) 10.4 (broad 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, 1), 3.6 (m, 1), 3.4 (m, 1), 2.8 (m, l), 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-ds) 11. 0 (broad 1), 7.9 (broad 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-fluorobenzyl) piperazine; NMR (DMS0-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, l), 3.7 (m, 1), 3.4 (m, 1), 3.3 (m, 1), 2.9 (, 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-f luorobenzyl) iperazine; NMR (CDC13) 7.6 (d, 1), 7.4 (d, 1), 7.3 (m, 2), 7.0 (, 3), 6.8 (s, 1), 6.3 (d, 1), 4.7 (m, 3 ), 4.1 (m, 1), 3.6 (m, 3), 3.0 (s broad, 1), 2.7 (broad d 1), 2.2 (d, 1), 1.3 (m, 3), 1.0 (m, 3 ) ppm; (trans) -1- ((2-chloro-4-carboxy enoxi) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((l-Nitroso-3,6-di (hydroxy sui fonyl) -naphthalen-2-yloxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-Nitroso-4-hydroxysulfonylnaphthalen-1-yloxy) ethyl) carbonyl -2,5-dimethyl -4- (4-f luorobenzyl) iperaz ina, - (trans) -1- ((3,6-di (hydroxysulfonyl) naphthalen-1-yloxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((3-Hydroxysulfonyl-6-aminonaphthalen-1-yloxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((3-Hydroxysulfonyl-7-aminonaphthalen-1-yloxy) methyl) carbonyl -2,5-dimethyl -4- (4-f luorobenzyl) piperaz ina, - (trans) -1- ( (5-hydroxysulfonylquinolin-8-yloxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2,3-dinitro-7-hydroxysulfonylnaphthalen-1-yloxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((2-carboxy-4-hydroxysulfonyl) enyl) enyl) methyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-amino-4-hydroxysulphonyl phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-f ormil-2,6-di-t-butyl phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4 - (Marpholin-4-yl) methyl -2,5-dimethyl-enoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (t rans) -l - ((4 - (methoxy carbonyl) -2,6-dichlorophenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4- (hydroxysulfonyl) naphthalen-1-yloxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((3,6-di (hidoxysulfonyl) -8-aminonaf talen-1-yloxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-carboxy-5-aminophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1 - ((4-trifluoromethyl-2, 3, 5, 6, -tetraf luorofenoxi) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-methoxy-4-f-ormyl-5- (2-hydroxy-3-methoxy-5 -f ormilf enyl) -phenoxy) methyl) carbonyl-2,5-dimethyl-4- ( 4-f luorobenzyl) 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; (trans) -1- ((2- (adamant-1-yl) -4-methylphenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4-di ((1-methyl-1-phenyl) ethyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-acetyl-4-bromophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-nitro-4-t-butylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-Acetyl-4-chloro-5-methylphenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-Acetyl-4-chloro-6-nitrophenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-Acetyl-4,6-dibromophenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-formyl -4,6-di (t-butyl) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3,5-dinitrofenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2,6-dichloro-4-ethoxycarboniifenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-ethoxycarbonyl-4-methylphenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-methoxy-6- (prop-3-enyl) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; "(traris) -1- ((3-fluoro-4-cyanophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-acetyl-4-) methyl-6-nitrophenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-methylbenzothiazol-5-yloxy) 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- (4- (trifluoromethyl) phenoxy) phenoxy) -methyl) carbanyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2 - (1H-pyrazol-3-yl) -4-chloro-5-methylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (lH -pyrazol-3-yl) -4-chlorophenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- (((2-phenyl-4-oxo-7 -hydroxy-4H-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) iperazine; (trans) -1- ((2-methoxy-4- (butoxymethyl) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (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) -1- ((2- (2H-Benzotriazol-2-yl) -4- (2-hydroxyethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((4-chlorophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((2- (methylthio) phenoxy) methyl) carbonyl -2, 5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((3,5-di (t-butyl) -4-formylphenoxy) ethyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((3,5-dibromo-4-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-diiodo-4-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-nitro-4-methoxycarbonylphenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2- (ethoxycarbonyl) indole-5-yloxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3- (2-carboxy-yl) phenoxy) -me il) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2,6-dinitro-4- (carboxymethyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-nitro-3-carboxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((6-carboxynaf such en-2-yloxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2,6-difluoro-4-ethylcarbonyl-enoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) - 1 - ((2 - (2 - (methoxycarbonyl) et il) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2- (prop-3-enyl) -4-acetylphenoxy) -methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- (((3-oxo-2H-benzofuran-6-yl) oxy) methyl) -carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2,4,6-rib-romo-3,5-dimethylphenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4- (heptylcarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-carboxy-4-acetyl-enoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-nitro-4-f-enylf-enoxy) -methyl) -carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) -perazine; (trans) -1- ((2-methoxy -4- (et-2-enyl) phenoxy) methyl) -carbonyl-2,5 -dimethyl-4 - (4-fluorobenzyl) piperazine, - (trans) -1 - ((2-Chloro-4-methoxycarbonylphene, methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2,6-diiodo-4-cyano-enoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine, - (trans) -1- ((2,6-diiodo-4-carboxy-enoxy) methyl) -carbonyl-2, 5-dimethyl -4- (4-f luorobenzyl) piperazine; (trans) -1- (((2-phenyl-4-oxo-4H-l-benzopyran-5-yl) oxy) methyl) carbonyl-2, 5-dimethyl- 4- (4-fluorobenzyl) iperazine; (trans) -1- (((2-phenyl-4-oxo-7-methoxy-4H-1-benzopyran-5-yl) oxy) methyl) carbonyl -2,5- dimethyl -4- (4-f luorobenzyl) -piperazine; (trans) -1- (((2-f-enyl-4-oxo -7-methoxy-2, 3-dihydro-4H-1-benzopyran-5- il) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-octyl carbonyl) enoxi) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- (((4- fta limid-1-ylf-enoxi) methyl) carbonyl -2,5-dimethyl-4 - (4-fluorobenzyl) piperazine, - (trans) -1- ((3- (morpholin-4-yl) phenoxy) methyl) carbonyl -2, 5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((3-chloro-4-bromofenoxi) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- (((2-oxo-7-methoxy-2H-1-benzopyran-8-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - ( trans) -1- ((2-acetyl-5-f luorofenoxyl) ethyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) 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-f luorobenzyl) iperazine; (trans) -1- ((2-f ormyl-3-methoxy-enoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f-luorobenzyl) -perazine; (trans) -1- ((2-amino-4-carboxy f-enoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-Chloro-4-carboxy-6-methoxy-enoxy) -methyl) -carbonyl-2, 5-dimethyl-4- (4-f-luorobenzyl) -perazine; (trans) -1- ((2,6-dimethyl-4-carboxyphenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; - (trans) -1 - ((2-methoxy -4- (2 - (carboxy) ethyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2,6-dimethoxy-4- (hydroxymethyl) phenoxy) -methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine, - (trans) -1- ( (2,6-dibromo-4-f ormilf enoxi) methyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((2-nitro-4- (ethoxycarbonyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-amino-4- (methoxycarbonyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4- (2 - (4-nitrophenyl) e t-2-enyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-acetyl-3,5-dimethoxy phenoxy) -yl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -l - ((2,6-di (t-butyl) -4 - (methoxy carbonyl) -phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-methoxy-4- (ethoxycarbonyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-cyclohexyl-4-chlorophenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2,6-dimethyl-4-chlorofenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-methoxy-4-ethylf-enoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((4-n-butylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- (((3-carboxy-l-bromonaf alen-2-yl) oxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- (-bromo-4-nitro-6-f ormilf enoxi) methyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((2-f ormil-4-chloro-enoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f-luorobenzyl) -perazine; (trans) -1- ((2,6-dichloro-4- (ethoxycarbonyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((4-Methyl-2-oxo-2H-l-benzopyran-6-yl) oxy) ethyl) 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) -1- (( 4- (2 - (4-nitrofenyl) et-2-yl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((2, 4 , 6-tribromo-3-formylphenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-benzyl-4-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2- (bezothiazol-2-yl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-nitro-6-fluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-ethoxy-4-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-bromo-4,6-di (t-butyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (pyrrolidin-1-yl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (morpholin-4-yl) phenoxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (piperidin-1-yl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-formyl-4-chloro-6-bromophenoxy) ethyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (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-2H-1-benzopyran-7-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-4-bromophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((2-chloro- 4 - bromo-6-methylphenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((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) -1- (((3- (hydroxysulfonyl) -7-aminonaphthalen-1-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((3- (methoxycarbonyl) naphthalen-2-yl) 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) iperazine; (trans) -1- ((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, 4,6-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) piperazine; (trans) -1- ((3-methoxy-4-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (t r a n s) - 1 - ((4 - (2 - (f e n i l) e t-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) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((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) iperazine; (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) -1- ((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-mercaptoophenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-nitro-6-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2,4-di (1-methylbutyl) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((3-trifluoromethyl-4-nitrophenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperizine, - (trans) -1- ((2,6-dibromo) -4- (methoxycarbonyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2,4-Dichloro-6-acetyl) methyl) carbonyl -2,5-dimethyl-4 - (4-fluorobenzyl) piperazin; (trans) -1- ((2-methoxycarbonyl-4-methyl-enoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-f ormyl-4-bromo-6-methoxy-enoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine, - (trans) -1- ((2,6-dif ormyl-4-methyl-enoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((2,6-dinitro-4-carboxy phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((2-nitro-4-acetyl-enoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-Formyl-4-nitro-β-raetoxifenoxi) methyl) -carbonyl-2,5-dimethyl-4- (4-f-luorobenzyl) piperazine; (trans) -1- ((4- (aminocarbonyl) methylphenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine, - (trans) -1- ((2-methoxycarbonyl-4) -methoxyphenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- (((2-phenyl-4-oxo-4H-l-benzopyran-6-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((2-chloro-4-trifluoromethyl-enoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-f-luorobenzyl) -piperazine; (trans) -1- ((2-carboxy-3-methyl-6-isopropyl-enoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f-luorobenzyl) piperazine, - (trans) -1- ( ((5,7-dibromo-2-methylquinolin-8-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- (((5,7-dichloro-2-methylquinolin-8-yl) oxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2,6-dino trofenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((2-nitro-4-methoxy-enoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-amino-4- (1,1-dimethylpropyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- (2,6-difnyl-4-aminofenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2,4-dichloro-3-methyl-6-aminofenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- (((2-oxo-4- (carboxy) methyl -2H-l-benzopyran-7-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- (((2-oxo-4-trif luoromethyl-2H-l-benzopyran-7-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) -piperazine; (trans) -1- ((2-t-Butyl-4-methoxy-enoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f-luorobenzyl) -perazine; (trans) -1- ((2-formyl-6-methyl-enoxy) methyl) carbonyl-2,5-dimethyl-4-fluorobenzyl) piperazin; (trans) -1- ((2-methoxycarbonyl-4-acetylphenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-bromo-5-fluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l - ((2,4-di (1,1-dimethylpropyl) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ( (3-methyl-4-fluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,3,4-trifluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,5-difluorophenoxy) 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-yl) oxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-aminocarbonyl-4-acetylphenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2,6-dinitro-3-t-butylphenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-fluoro-4-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-3-fluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (2-ethylhexoxy) carbonylphenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4,6-tribromo-4-carboxyphenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4- (4-bromophenyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((4- (4-carboxyphenyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((2,3,6) -trifluorophenoxy) methyl) carbonyl-2-, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4,5-trifluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4,6-trifluorophenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-Fluoro-5-trifluoromethylphenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((2,4-dinitroaphthalen-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) -1- ((2-Acetyl-4-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-dimethyl-4- (1- (3,5-dimethyl-4-hidoxyphenyl) -l-methylethyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((4 - (3 - (4-hydroxy-f-enyl) -Ex-2-yl) -phenoxy) -methyl) -carbonyl-2, 5-dimethyl-4- (4-f-luorobenzyl) -piperazine; (trans) -1- (((6- (hydroxysulfonyl) naphthalen-2-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-Chloro-4-methyl-enoxy) -methyl) -carbonyl-2,5-dimethyl-4- (4-f-luorobenzyl) -piperazine; (trans) -1- ((2-bromo-4,5-difluorofenoxyl) methyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-chloro-4-methoxyphenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((2-methoxy-4-chloro-enoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((4- (2- (me t oxycarbonyl) ethyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2,6-difnyl-4-n-trofenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((2-amino-3-methylphonoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-methyl-4-f luorofenoxyl) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-methyl-4-yodofenoxyl) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-f luoro-6-methoxy-enoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) 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) -1- ((2-carboxy-6-isopropylphenoxy) met yl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (piperidin-1-yl) -4-methylphenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((2,3-Dihydro-2, 2-dimethylbenzofuran-7-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) 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-fluorobenzyl) piperazine; (rans) -1- (((phenan ren-9-yl) oxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((2-nitro) 4-bromophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((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-fluorobenzyl) piperazine; (trans) -1- ((2-chloro-4-aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-formyl-4-bromo-6-nitrophenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-4- (acetyl) methylphenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((4- (5-mercaptotetrazol-1-yl) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4,6-triiodo-3- (2-carboxy) butylphenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-Hydroxymethyl-4-nitrophenoxy) methyl) -carbonyl-2,5-dimethyl- (4-fluorobenzyl) piperazine; (trans) -1- ((2.3, 5, 6-tetrafluoro-4- (2,3,4,5,6-pentafluorophenyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (benzotriazol-2-yl) -4,6-di (1,1 -dimethylpropyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-phenyl-3-hydroxy-4-oxo-4H-l-benzopyran-6-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) - piperazine; (trans) -1- ((indanonyl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-nitro-4- (hydroxysulfonyl) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-nitro-3-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((4- (2,4-dini-phenyl) aminophenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-methyl-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) iperazine; (trans) -1- ((2,6-diiodo-4-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-formyl-4-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -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) -1- ((2-amino-4-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-amino-4-carboxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-amino-4-t-butylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-amino-4-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methyl-3-aminophenoxy) 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) -1- ((3-methyl-4-aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -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) -1- ((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) iperazine; (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) -1- ((2-hydroxymethyl-6-methoxyphenoxy) methyl) -carbonyl-2; 5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2,3-dimethoxyphenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4- (methoxycarbonyl) -5-methoxyphenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-4- (methoxycarbonyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((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) -1- ((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) iperazine; (trans) -1- ((2,6-di (t-butyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4-di (t-butyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3,5-di (t-butyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-di (isopropyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - trans) -1- ((2-methoxy-4) - (ethoxycarboni) methylphenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; trans) -1- ((2-ethoxy-5-prop-2-enylphenoxy) met yl) -carbonyl-2-dimethyl-4- (4-fluorobenzyl) piperazine, - trans) -1- ((2-methoxy) -5-prop-2-enylphenoxy) methyl) -carbonyl-2-5-dimethyl-4- (4-fluorobenzyl) piperazine; trans) -l - ((2,6-di (1-methylapropyl) phenoxy) methyl) -carbonyl-2-5-dimethyl-4- (4-fluorobenzyl) piperazine; trans) -1- ((2,4-difluorophenoxy) methyl) carbonyl -2,5-dimethyl-4-fluorobenzyl) piperazine; trans) -1- ((2,6-diphenyl-phenoxy) -yl) -carbonyl-2, 5-dimethyl-4-fluorobenzyl) iperazine; trans) -1- ((2-nitro-3-trifluoromethylphenoxy) methyl) -carbonyl-2-dimethyl-4- (4-fluorobenzyl) piperazine, -trans) -1- ((2-cyclopentyphenoxy) methyl) carbonyl- 2,5-dimethyl-4- [4-fluorobenzyl] piperazine; trans) -1- ((4-cyclopentylphenoxy) methyl) carbonyl -2,5-dimethyl-4- '4-fluorobenzyl) piperazine; trans) -1- ((2,3-difluorophenoxy) methyl) carbonyl -2,5-dimethyl-4-? -fluorobenzyl) iperazine; trans) -1- ((2-carboxy-6-aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- [4-fluorobenzyl] piperazine; trans) -1- ((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) -1- ((2,4 -dicarboxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,3-dimethylo-5-formylphenoxy) ethyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (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) -1- ((3-methyl-4-isopropylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((Fluoren-2-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (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) -1- (((2-Oxo-3, 4, 8-trimethyl-2H-l-benzopyran-7-yl) oxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-Acetyl-4-fluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-fluoro-4-bromophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((2- (methylcarbonyl) amino) -5-methylphenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((1-Acetylnaphthalen-2-yl) oxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((2- methoxy-4-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((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- (((1-aminonaf-alen-2-yl) oxy) methyl) carbonyl-2,5-dimethyl- (4-fluorobenzyl) piperazine; (trans) -1- ((4-aminonaphthalen-1-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-4- (1,2-dihydroxyethyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((3- (2-aminoethyl) indolin-5-yl) oxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1 - (((5-chloroquinolin-8-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-methoxy-4 - (2 - (amino) ethyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4- (2- (amino) ethyl) f enoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1 - ((2-methoxy -4 - (2 - (amino) et yl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2,4-di-amino phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-aminofenoxyl) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (diethylamino) ethyl-4-aminofenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-methyl-5- (2-aminobutyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((2- (Benzotriazol-2-yl) -4- (1,1,3,3-tetramethylbutyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorsbenzyl) iperazine; (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-dimethyl-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) me il) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2,6-dichloro-3-carboxy phenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-methoxy-4-carboxy-enoxy) methyl) carbonyl-2, 5 -dimethyl-4-fluorobenzyl) piperazine, - (trans) -1- ((2,6-dimethoxy-) 4-carboxyphenoxy) -methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4- (2-carboxyethyl) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((2- (2-Hydroxyethyl) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((3- (2-Hydroxyethyl) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((4- (2-Hydroxyethyl) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-methoxy -4 - (2-hydroxyethyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2,4-dibromo-6-f ormilf enoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-f luoro-6-f ormilf enoxi) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((2,4-dichloro-6-f ormilf enoxy) methyl) -carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2,4-diiodo-6-f ormilf enoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-methoxy-6-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((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-dimethoxy-methoxy) methyl) -carbonyl-2-yl-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((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-methoxynaphthalene-1 -yl) oxy) methyl) carbonyl-2,5-dimethyl (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-5,6-dimethoxyphenoxy) methyl) -carbonyl-2-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((3-nitro) 4-methoxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- (((fluoren-9-on-1-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((4-Hydroxy-1,2,3,4-tetrahydronaphthalen-8-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) -piperazine; (trans) -l - ((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) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2, 3, 4-trichlorophenoxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methyl-4-bromo-6-chlorophenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-Chloro-4-fluorophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-flurobenzyl) piperazine; (trans) -1- ((2,4,6-trimethiophenoxy) 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- ((3-formylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- (((1-bromonaphthalen-2-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- ( 4-fluorobenzyl) piperazine, - (trans) -1- (((1,6-dibromonaphthalen-2-yl) oxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((L-nitrosonaphthalen-2-yl) oxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- (((2,4-dichloronaphthalen-1-yl) oxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- (((2-nitronaphthalen-1-yl) oxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((2-carboxynaphthalen-1-yl) oxy) me yl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((2-methylnaphthalen-1-yl) oxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((3- (hydroxysulfonyl) -7- (dimethylamino) -naphthalen-1-yl) oxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- (((4-methoxynaphthalen-1-yl) oxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((1-formylnaphthalen-2-yl) oxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- (((1-carboxynaphthalen-1-yl) oxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((L-amino-4- (hydroxysulfonyl) naphthalen-2-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4- (naphthalen-2-yl) aminophenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((3-aminonaphthalen-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) -1- ((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) iperazine; (trans) -1- ((4-hydroxymethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (hydroxymethyl) -4-bromophenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-di (hydroxymethyl) -4-methylphenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy -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) -1- (((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; (trans) -1- (((indol-4-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, • (trans) -1- (((indol-5- il) 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) iperazine; (trans) -1- (((2-methylquinolin-8-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- (((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) iperazine; (trans) -1- (((5-nitroquinolin-8-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((quinolin-5-yl) oxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- (((5- (hydroxysulfonyl ) -7-iodoquinolin-8-yloxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- (((2-phenyl-4-oxo-4H-1) -benzopyran-7-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-2, 5,7, 8-tetramethyl- 2, 3-dihydro-l-benzopyran-6-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- (((2-Oxo-3-chloro-4-methyl-2H-l-benzopyran-7-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((2-Oxo-3- (diethylamino) methyl) -4-methyl-2H-1-benzopyran-7-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- ( 4-fluorobenzyl) piperazine; (trans) -1- (((2-oxo-6-methyl t-oxy-2H-1-benzopyran-7-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- (((2 -oxo-2 H-l-benzopyran-7-yl) oxy) methyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-methoxy-4-formyl-6-bromophenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((2 -methoxy-4-formyl-6-iodophenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-4-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((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) -1- ((2,4-dichloro- 6-nitrophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4-dinitro-6-formylphenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4-dinitro-6-carboxy phenoxy) 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) -1- ((2,5-dinitrofenoxi) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-nitro-5-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-nitro-4-chlorophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - trans) -1- ((2,4-dinitrofenoxy) methyl) ) carbonyl -2,5-dimethyl-4-fluorobenzyl) piperazine; trans) -1- ((2-nitro-4-formylphenoxy) methyl) carbonyl-2, 5-dimethyl-4-fluorobenzyl) piperazine, - trans) -1- ((2-nitro-4-formyl-6 -methoxyphenoxy) methyl) -carbonyl-2-5-dimethyl-4- (4-fluorobenzyl) piperazine; trans) -1- ((2-nitro-4-carboxyphenoxy) methyl) carbonyl-2,5-dimethyl-4-fluorobenzyl) piperazine; trans) -1- ((2-nitro-4-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4-fluorobenzyl) piperazine; trans) -1- ((2,6-dinitro-4-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; trans) -1- ((2-nitro-4- (carboxymethyl) phenoxy) methyl) -carbonyl-2-dimethyl-4- (4-fluorobenzyl) piperazine; trans) -1- ((2,6-dichlorophenoxy) methyl) carbonyl -2,5-dimethyl-4,4-fluorobenzyl) piperazine; trans) -1- ((3-methoxy-5-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4,4-fluorobenzyl) piperazine; trans) -1- ((4-cyanophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; trans) -1- ((4- (1-methyl-l-phenylethyl) phenoxy) methyl) -carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) iperazine; t rans) - 1 - ((3 - (et ylamino) -4-met il f-enoxy) methyl) -carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) 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-fluorobenzyl) 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 - il) oxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) 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-fluorobenzyl) iperazine; (rans) -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) -1- ((3-trifluoromethoxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((2-methyl-5-aminophenoxy) me il ) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((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) -1- ((3-methylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-methylphenox) ethyl) 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) ethyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- (((2 -oxo- 1,3-benzoyl-2-on-6-yl) oxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -l - (((2-phenyl-4-oxo-4H-1-benzopyran-3-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((2-oxo-4-methyl-2H-1-benzopyran-7-yl) oxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((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- (4-fluorobenzyl) piperazine; (trans) -1- (((2-phenyl-4-oxo-2,3-dihydro-4H-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) ethyl) 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 ") -l - (((5,6,7,8-tetrahydronaphthalen-2-yl) oxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) - 1- ((2,4,6-tribrornophenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-dibromo-4-cyanophenoxy) methyl) ) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-fluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; trans) -1- ((2,3,5,6-tetrafluorophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (t ans) -1- ((2,6-difluorophenoxy) ) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,3-dichlorophenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,3, 6-trichlorophenoxy) ethyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((2-chloro-4, 5-dimethylphenoxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,5-Dichlorophenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (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) ethyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2 - (benzyloxy) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-ethoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-phenylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (methoxycarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl (4-fluorobenzyl) piperazine; (trans) -1- ((2- (ethoxycarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-Acetylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (ethylcarbonyl) phenoxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (t-Butyl) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-isopropylphenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((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-trime-ilphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4-dime-ilphenoxy) 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) iperazine; (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) iperazine; (trans) -1- ((2,6-dimethoxyphenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-prop-3-enyl-6-methyl-phenoxy) -yl) -carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((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; (rans) - 1 - ((2-n-propyl phenoxy) me il) 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) ethyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((3-chloro-4-fluorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3,5-Dichlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (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) ethyl) 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) iperazine; (trans) -1- ((3-trifluoromethylphenoxy) methyl) carbonyl-2,5-dimethyl (4-fluorobenzyl) piperazine; (trans) -1- ((3-t-butylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((3-isopropylphenoxy) me il) 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- ((3,4-dimethylphenoxy) ethyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((2-t-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) -1- ((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- (4-fluorobenzyl) piperazine, - (trans) -1- ((2-isopropyl-4- chloro-5-methylphenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((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-butoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-n-e-toxyphenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((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-tetramethoxybutyl) phenoxy) -methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1 - ((4 - (1, 1-dimethylpropyl) phenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((4- (1-methylpropyl)) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((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) -1- ((2- (t-butyl) -4-me-ilphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3- (ethylamino) -4-methyl-phenoxy) -yl) -carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) -perazine; (trans) -1- ((4- (methoxycarbonyl) methylphenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-ethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-n-propyl phenoxy) and il) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-carboxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-4,6-dibromophenoxy) -yl) -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-diiodophenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-carboxy-6-methoxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((2-carboxy-6) -methylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-carboxy-5-chlorophenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-carboxy-5-methoxyphenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (( 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) iperazine; ) -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- (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) -1- ((2,3,4,5,6-pentachlorophenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans ") -1- (( 2, 4, 5-trichlorophenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-methoxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4 - (4-fluorobenzyl) piperazine; (trans) -1- ((3- (methoxycarbonyl) phenoxy) ethyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (( 3- (ethoxycarbonyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((4-bromophenoxy) methyl) carbonyl-2, 5-dimethyl-4 - (4-fluorobenzyl) iperazine; (trans) -1- ((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) iperazine; (trans) -1- ((2-isopropyl-4-chloro-5-methylphenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-ethoxy-enoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2- (t-butyl) -4-methyl-enoxy) -methyl) -carbonyl-2, 5-dimethyl-4- (4-f-luorobenzyl) -piperazine; (trans) -1- ((3-formyl-4-nitrofenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-methoxy-4-prop-3-enylf-enoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-f-luorobenzyl) piperazine; (trans) -1- ((2- (1-phenylethyl) -4-chloro-enoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4- (ethoxycarbonyl) methylphenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((4-trif luoromet oxyf enoxi) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((3-fluoro-4-chlorofenoxi) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine, - (trans) -1- ((2-f luoro -4-chloro-enoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine, - (trans) -1- (((7-methoxynaphtalen-2-yl) oxy) - methyl) - carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-benzyloxy-4-cyano-enoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) 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-dimethyloxy-phenoxy) -yl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-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-yl-3-nitrophenoxy) me il) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (rans) -1- ((3,5-dimethylophenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-nitro-3-carboxy-6-methylphenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((3 -cyanophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-methoxy-5-nitrophenoxy) methyl) carbonyl-2, 5-dimethyl- (4-fluorobenzyl) piperazine, - (trans) -1- ((2-nitro-5-carboxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3- (carboxymethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methoxy-5-carboxyphenoxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4- (dimethylamino) methylphenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4- (2 - (dimethylamino) ethylphenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((3 -carboxyphenoxy) ethyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((naphthalen-1-yl) oxy) methyl) carbonyl -2,5-dimethyl-4 - (4-fluorobenzyl) piperazine, - (trans) -1- (((5-aminonaphthalen-1-yl) oxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-nitro-4-aminophenoxy) ethyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-di (t-butyl) -4-methylphenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((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) -1 - ((2-nitro-4-aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4- (benzyloxy) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4- (aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fuorobenzyl) piperazine; (trans) -1- ((3,5-di (trifluoromethyl) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2,4-dibromophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((2,6-dibromo-4-) methylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,4-dichlorophenoxy) ethyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((3,5-dimethyl-4-bromophenoxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((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) iperazine; (trans) -1- ((2,6-dichloro-4-carboxy phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- (((2-carboxyquinolin-4-yl) oxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-dimethyl-4-f ormilf enoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2,6-di (t-butyl) -4-carboxy-f-enoxy) -methyl) -carbonyl-2,5-dimethyl-4- (4-f-luorobenzyl) -perazine; (trans) -1- ((2-amino-5-carboxyphenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2,6-di (t-butyl) -4- (hydroxymethyl) -phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- (((4-carboxyquinolin-2-yl) oxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((3-nitro-4-chlorofenoxi) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((3-yl- 4-chloro-5-methyl-enoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((3,5-di (raetoxycarbonyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2- (morpholin-4-yl) methyl-4-carboxy enoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-methoxy-4-cyanofenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-chloro-4-bromo-enoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-trif luoromethyl-enoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((2-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-methyl-4-acetylphenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((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-dimethyl phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-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) -1- ((4-acetylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((4-benzylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((2-methoxy-4-carboxyphenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- (((3-carboxinaphthalen-2) - il) 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- (carbonyl) phenoxy) methyl) carbonyl -2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((3,5-dimethoxyphenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((2- (cyclohexyl) phenoxy) 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- ((2,4-dichloro-3-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,5-dimethyl-phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-bromophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((3- (methylcarbonyl) aminophenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((3-Acetylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((3-trifluoromethylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((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-formylphenoxy) 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) -1- ((2-nitro-5-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((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) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-nitro-4-aminophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-dichloro-4-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-Fluoro-4-nitrophenoxy) ethyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - (trans) -1- ((2,3-difluoro- 6-nitrophenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-Chloro-4-nitrophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-nitro-4-cyanophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2-bromo-4-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3,4-Dichlorophenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3,5-Dichlorophenoxy) -l, yl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (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) iperazine; (trans) -1- ((3,5-dimethyl-4-chlorophenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-methoxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((4- (methoxycarbonyl) phenoxy) methyl) carbonyl-2, 5-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) -1- ((4-isopropylphenoxy) methyl) carbonyl- 2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((naphthalen-2-yl) oxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (((6-bromonaf alen-2-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((3- (hydroxymethyl) phenoxy) methyl) 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) -1- (((1,3-benzodioxolan-5-yl) oxy) me il) - carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((2,6-dimethyl-4-nitrophenoxy) ethyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (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) -1- ((3- (aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4 - (4-fluorobenzyl) iperazine; (trans) -1- ((3- (methoxycarbonyl) methyl) enoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2- (4-f-enylcarbonyl) -4-f-luo-enoxy) -methyl) -carbonyl-2,5-dimethyl-4- (4-f-luorobenzyl) -piperazine; (trans) -1- ((2- (1-methyl) cyclohexyl-2,4-dimethyl-enoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f-luorobenzyl) -perazine; (trans) -1- ((2- (benzyloxycarbonyl) f enoxy) met yl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((2- (4- (methyl) f-enylcarbonyl) -5-methoxy-enoxy) -methyl) -carbonyl-2, 5-dimethyl-4- (4-f-luorobenzyl) -piperazine; (trans) -1- ((2-phenylcarbonyl-5-octoxyphenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; trans) -1- ((4-octyl-enoxy) -methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) -perazine; (trans) -1- ((2 - (2 - (carboxy) phenylcarbonyl-5-di (n-butyl) aminofenoxi) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; ) -1- ((2-f-enylcarbonyl-5-methoxy-enoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-f-luorobenzyl) piperazine; (trans) -1- ((2-methoxy-4) - (3-hydroxyprop-2-enyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- (((3- (f-enylaminocarbonyl) naphthalen-2-yl) oxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- (((6- (f-enylcarbonyl) naphthalen-2-yl) oxy) -methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2- ((2-phenylethyl) carbonyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4- ((4-f luorofenyl) carbonyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2- (phenylamino) carbonylphenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((2-f-enylcarbonyl phenoxy) methyl) carbonyl -2,5-dimethyl-4 - (4-fluorobenzyl) piperazine, - (trans) -1- ((2-f) enylcarbonyl- 4-chloro-5-methyl-enoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4- (4-chlorofenyl) carbonyl) enoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-luorobenzyl) piperazine; (trans) -1- ((4-benzylcarbonyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4 - (4-fluorobenzyl) piperazine, - (trans) -1- ((2-f) enylcarbonyl-4- methyl-enoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((4- (2-methylcarbonylethyl) phenoxy) methyl) -carbonyl-2, 5 -dimethyl-4 - (4f-luorobenzyl) piperazine, - (trans) -1- ((4-f-enylcarbonyl) enoxi) methyl) carbonyl -2,5-dimethyl-4- (4f luorobenzyl) piperazine; and (trans) -1- ((3-phenylcarbonylphenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine.

C. In a similar manner, the following compounds of formula (Ib) are prepared: 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-4- (benzyl) piperazine; NMR (CDC13) 7.6 (m.3), 7.5 (m, 4), 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; 1- ((3-methoxyphenoxy) methyl) carbonyl-4- (benzyl) piperazine; NMR (CDC13) 7.3 (m, 5), 6.5 (m, 4), 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 (CDC13) 7.8 (m, 2), 7.4 (m, 3), 6.8 (d, 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 (CDC13) 7.3 (m, 7), 7.0 (m, 3), 4.7 (s, 2), 3.6 (m, 6), 2.4 (m, 4) ppm; 1- ((4-chloro-enoxy) -me il) carbonyl-4- (benzyl) piperazine and 1- (chloro) acetyl-4- (benzyl) piperazine; NMR (CDC13) 7.3 (m, 7), 6.9 (, 2), 4.6 (s, 2), 3.6 (m, 6), 2.4 (m, 4) ppm; 1- ((3-cyano-enoxy) methyl) carbonyl-4- (benzyl) piperazine, -NMR (CDC13) 7.3 (m, 2), 7.0 (4), 6.8 (m, 3), c, 2), 4.2 (d, 1), 3.9 (d, 2), 3.6 (m, 3), 3.0 (m, 3), 2.6 (m, 2) ppm; 1- ((4-cyano-enoxy) -methyl) -carbonyl-4- (benzyl) piperazine; NMR (CDC13) 7.6 (m, 4), 7.4 (m, 3), 7.0 (d, 2), 4.9 (c, 2), -4.6 (d, 1), 4.3 (d, 2), 4.0 (d , 2), 3.6 (t, 1), 3.4 (d, 2), 3.0 (m, 2) ppm; 1- ((3 - (1-methylimidazolin-2-yl) phenoxy) methyl) carbonyl-4- (benzyl) iperazine; NMR (CDC13) 7.5 (m, 6), 7.2 (m, 3), 5.0 (d, 2), 4.0 (, 4), 3.3 (c, 4), 3.0 (m, 6) ppm; 1- ((4-chloro-2-aminocarbonylf-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; NMR (DMSO-ds) 8.7 (s, 1), 7.8 (s, 1), 7.7 (s, 1), 7.6 (dd, 1), 7.4 (c, 3), 7.2 (d, 1), 5.0 ( s, 2), 3.4 (broad d 4), 3.3 (s, 2), 2.4 (broad d 4) ppm; 1- ((5-chloroquinolin-8-yloxy) methyl) carbonyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-de) 9.0 (s, 1), 8.5 (d, 1), 7.75 (dd, 1), 7.65 (d, 1), 7.4 (c, 2), 7.1 (d, 1), 5.1 ( s, 2), 3.5 (m, 6), 2.4 (broad d 4) ppm; 1- ((3-trif luoromet oxy phenoxy) me useful) carbonyl-4- (benzyl) piperazine; 1- (3- (3,4,5-trimethoxy phenoxy) propyl) carbonyl -4 - (benzyl) piperazine, - l- (1- (3,4,5-trimethoxyphenoxy) propyl) carbonyl-4- (benzyl) iperazine; 1- (1- (3,4,5-t rime tox i phenoxy) pentyl) carbonyl-4- (benzyl) piperazine; 1- ((4-methoxyphenoxy) methyl) carbonyl-4- (benzyl) iperazine; 1- ((3,5-dimethoxyphenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((3-chloro-enoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- (1- (3,4,5-trimethoxyphenoxy) ethyl) carbonyl-4- (benzyl) piperazine; 1- ((3,4-dichloro-enoxy) 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-nitrofenoxi) methyl) carbonyl-4- (benzyl) piperazine; 1- (1- (3,4,5-trimethoxy phenoxy) septyl) carbonyl-4- (benzyl) piperazine, 1- (1- (3,4,5-trimethyl oxy phenoxy) -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-f luorofenoxi) ethyl) carbonyl-4- (benzyl) piperazine; 1 - ((4-trif luoromet ilf enoxi (methyl) carbonyl-4- (benzyl) piperazine; 1- (((4-chlorofenyl) thio) methyl) carbonii-4- (benzyl) piperazine; chlorophenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((4- (benzyloxy) phenoxy) methyl) carbonyl-4- (benzyl) piperazine; 1- ((4- (methoxycarbonyl) phenoxy) methyl) carbonyl-4- (benzyl) piperazine; l - ((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, - i - ((4- (2,2-dimethylethyl) phenoxy) ethyl) carbonyl-4 - (benzyl) piperazine; 1- ((4 - (acetyl) f enoxi) methyl) carbonyl -4 - (benzyl) piperazine; l - ((naph talenyl-2-oxy) methyl) carbonyl -4 - (benzyl) iperazine; l- ((4-Chloro-3,5-dimethyl-yl-enoxy) -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) iperazine; 1- ((2,3,4,5,6-pentaf luorofenoxi) methyl) carbonyl -4- (benzyl) piperazine; 1- ((2- (benzyloxy) -4-cyano-enoxy) methyl) carbonyl-4- (benzyl) iperazine; 1- ((2-chloro-4-bromophenoxy) methyl) carbonyl-4- (benzyl) iperazine; 1- ((3-bromophenoxy) methyl) carbonyl -4- (benzyl) piperazine; 1- ((3,5-trif luoromet ilf enoxi) methyl) carbonyl-4- (benzyl) piperazine, - 1 - (((5 - 0x0 - 6, 7, 8 - trihydronaf talen - 1 - yl) oxy) methyl ) carbonyl-4- (benzyl) piperazine; 1- (((2-oxo-2H-1-benzopyran-4-yl) oxy) methy) carbanyl-4- (benzyl) iperazine; l -, ((2-cyanofenoxi) methyl) carbonyl -4- (benzyl) piperazine; 1- ((4-methyl-3,5-dibromo phenoxy) ethyl) carbonyl -4 - (benzyl) piperazin, - "l - ((quinolinyl-6-oxy) methyl) carbonyl -4 - (benzyl) piperazine, 1- (((difnyl) petoxy) methyl) carbonyl -4 - (benzyl) piperazine; 1- ((3- (morpholin-4-yl) phenoxy) methyl) carbonyl-4- (benzyl) piperazine; hydrochloride salt of 1- ((2-bromofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((pindinyl-3-oxy) ethyl) carbonyl-4- (benzyl) piperazine; 1 - ((2 - (benzyl) f enoxi) ethyl) carbonyl-4- (benzyl) iperazine; 1 - . 1 - ((4 - (benzyl) phenoxy) methyl) carbonyl-4 - (benzyl) piperazine, - 1 - ((4 - (f ormyl) f enoxy) ethyl) carbonyl-4 - (benzyl) piperazine; 1- ((2- (prop-3-enyl) phenoxy) methyl) carbonyl-4 - (4-chlorobenzyl) piperazine, -1- ((2,6-dibromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((benzothiazolyl-2-oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, 1- ((4-cyclohexylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (benzyloxy) carbonylf enoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((5-chloroquinolinyl-8-oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; l - "((4 - (imidazol-1-yl) phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine, 1- ((3-chloro-5-methyl) phenoxy) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine; 1 - ((4-carboxy-enoxi) methyl) carbonyl-4 - (benzyl) iperazine; hydrochloride salt of 1- ((4-iodophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; NMR (DMS0-d6) 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) piperazine, -1- ((2,6-dimethoxyphenoxy) methyl) carbonyl-4- (4 -chlorobenzyl) piperazine; 1 - ((2-y-ylquinolinyl-4-oxy) me yl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- (((2,3-dihydro-lH-inden-5-yl) ) oxy) ethyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((coumarin-4-yloxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-chlorobenzyloxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1 - (((4-chlorofenyl) amino) methyl) carbonyl-4- (4-chlorobe) hydrochloride ncil) iperazine; NMR (DMSO-dg) 11.4 (broad 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-chloronaf talenyl-1-oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, - 1- (((4-chlorophenyl) (methyl) amino) methyl) carbonyl -4- (4- chlorobenzyl) iperazine; 1- (((di (4-chloro) phenyl) methoxy) methyl) carbonyl -4- (chlorobenzyl) piperazine, 1- ((3,5-dimethoxy-4-chloro-enoxy) methyl) carbonyl -4- (4-chlorobenzyl) iperazine; NMR (CDC13) 7.2 (c, 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-f ormilf enoxi) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine, - hydrochloride salt of 1- ((3-f luoro-4-chlorofenoxi) methyl) carbonyl -4- (4- chlorobenzyl) piperazine; NMR (DMSO-dg) 11.8 (s, 1), 7.5 (, 5), 7.1 (d, 1), 6.8 (d, 1), 5.0 (c, 2), 4.3 (m, 3), 3.9 (m, 1), 3.6-2.9 (m, 6) ppm; 1- ((2- (hydroxymethyl) f enoxi) met il) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2,4-dibromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2,4-dichloro-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, -l- ((4-chloro-3-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; NMR (DMSO-d6) 7.6 (m, 6), 7.3 (d, 1), 5.0 (c, 2), 4.3 (m, 3), 3.9 (m, 1), 3.5-2.9 (m, 6 ) ppm; 1- ((4-bromo-2-f ormilf enoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; NMR (DMS0-ds) 11.4 (broad s, 1), 7.8 (m, 2), 7.5 (m, 4), 7.2 (d, 1), 5.2 (c, 2), 4.4 (m, 3), 4.0 (m, 1), 3.6-2.9 (m, 6) ppm; 1- ((2-methoxy-5-nitro-enoxy) ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - ((4-methyl-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - ((4-bromo-2-chloro-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine hydrochloride salt; hydrochloride salt of 1- ((2-methyl-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; s a l l l o r h i d r a t o d o 1 - ((3,5-dimethyloxy en)) methyl) carbonyl -4- (4-chlorobenzyl) iperazine; 1- ((2-aminocarbsnil-4-chlorofenoxi) methyl) carbonyl-4- (4-fluorobenzyl) piperazine; NMR (DMS0-d6) 8.7 (broad s, 1), 7.8 (s, 1), 7.7 (s, 1), 7.6 (dd, 1), 7.2 (m, 3), 7.2 (d, 1), 5.0 (s, 2), 3. 5 (m, 6) ', 2.4 (m, 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 (, 4) ppm; 1- ((3-formyl -4-nitrophenoxy) met il) carbonyl-4- (4-fluorobenzyl) 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) naph such in -2-yloxy) ethyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2-Nitroso-4-hydroxysulfonylnaphthalene-1-yloxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; l- ((3,6-di (hydroxysulfonyl) naphthalen-1-yloxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-Hydroxysulfonyl-6-aminonaphthalen-1-yloxy) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine, 1- ((3-hydroxysuifonyl-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-hydroxysulfonylnaphthalen-1-yloxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-4-hydroxysulfonyl-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-amino-4-hydroxysulfonyl-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; , 1- ((4-formyl -2,6-di-t-butyl phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((4- (morpholin-4-yl) met ilf enoxi) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((4- (methoxycarbonyl) -2,6-di chloro phenoxy) methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (hydroxysulfonyl) naph talen-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-aminofenoxi) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((4-trif lur orne til -2,3,5,6, -tet raf luorof enoxi) -methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - ((2-methoxy-4-formyl -5- (2-hydroxy-3-methoxy-5-f ormilf enyl) phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine, - 1 - ((4 - carboxy 2,3,5,6-tet raf luorofenoxi) methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1 - ((4 - (adaman t-1-yl) phenoxy) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine; 1- ((2- (adamant-1-yl) -4-methyl-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) -perazine; 1- ((2,4-di ((1-methyl-1-f-enyl) -ethyl) -phenoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) -piperazine; 1- ((2-acetyl-4-bromo-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) -perazine; 1- ((2-nitro-4-t-butyl) enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-acetyl-4-chloro-5-met-il-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-acetyl-4-chloro-6-nitrophenxoi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-acetyl-4,6-dibromofenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2-formyl-4,6-di (t-butyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3,5-dinitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2,6-dichloro-4-ethoxycarbonyl) enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-ethoxycarbonyl-4-methyl-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-6- (prop-3-enyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; l- ((3-fluoro-4- cyanofenoxi) ethyl) c-rbonyl -4 - (4-chlorobenzyl) piperazine; 1- ((2-acetyl-4-methyl-6-nitrofenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2-methylbenzothiazol-5-yloxy) methyl) carbonyl -4- (4-chlorobenzyl) iperazine; 1- ((2-carboxy-4- (hydroxysulfonyl) phenoxy) methyl) -carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((4- (4- (trifluoromethyl) phenoxy) f-noxy) -methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (lH-pyrazol-3-yl) -4-chloro-5-methyl-enoxy) methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (lH-pyrazol-3-yl) -4-chloro-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- (((2-f-enyl-4-oxo-7-hydroxy-4H-1-benzopyran-3-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-Chloro-3-trifluoromethyl-enoxy) 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-methoenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2,5-di (t-butyl) -4-methoxy-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-formyl-4-methylfenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (2H-benzotriazol-2-yl) -4- (2-hydroxyethyl) -phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((4-chloro-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 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) iperazine; 1- ((2,6-dinitro-4- (carboxymethyl) phenoxy) -methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-3-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((6-carboxynaphthalen-2-yloxy) methyl) carbonyl -4- (4-chlorobenzyl) iperazine; 1- ((2,6-difluoro-4-ethylcarbonylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2- (2- (methoxycarbonyl) ethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (prop-3-enyl) -4-acetylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 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) iperazine; 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) met i) carbonyl-4 - (4-chlorobenzyl) iperazine; 1- ((2-methoxy-4- (et-2-enyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-Chloro-4-methoxycarbonylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2,6-diiodo-4-cyanophenoxy) me il) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2,6-diiodo-4-carboxyphenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine, - 1- (((2-phenyl-4-oxo-4H-1-benzopyran-5-yl ) oxy) methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-phenyl-4-oxo-7-methoxy-4H-1-benzopyran-5-yl) oxy) ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-phenyl-4-oxo-7-methoxy-2,3-dihydro-4H-l-benzopyran-5-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; l- ((4-octylcarbonyl) enoxy) 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-bromo-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-OXO-7-methoxy-2H-1-benzopyran - 8 -yl) oxy) -methyl) carbonyl-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-imethylcyclohex-1-yl) -5-methylbenzyl) phenoxy) ethyl) carbonyl-4- (4 -chlorobenzyl) iperazine; 1- ((2-formyl-3-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-amino-4-carboxy phenoxy) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine, - 1- ((2-chloro-4-carboxy-6-methoxy-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dimethyl-4 - carboxy phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4- (2- (carboxy) ethyl) phenoxy) m and il) - carbonyl -4- (4-chlorobenzyl) iperazine; 1- ((2,6-dimethoxy-4- (hydroxymethyl) phenoxy) -methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dibromo-4-f ormilf enoxy) methyl) carbonyl -4- (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-enyl) phenoxy) methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-acetyl-3,5-dimethoxy phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) iperazine; 1- ((2,6-di (t-butyl) -4 - (methoxycarbonyl) phenoxy) -methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2-methoxy-4- (ethoxycarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-cyclohexyl-4-chlorofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dimethyl-4-chloro-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4-ethylphenoxy) -me il) carbonyl-4 - (4-chlorobenzyl) piperazine; 1- ((4-n-butyl) enoxy) methyl) carbonyl-4- (4-chlorobenzyl) -piperazine; 1- (((3-carboxy-1-bromonaf talen-2-yl) oxy) methyl) -carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2-bromo-4-nitro-6-formylf-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - ((2-formyl-4-chlorofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, 1- (2,6-dichloro-4- (ethoxycarbonyl) phenoxy) -methyl) carbonyl-4 - (4-chlorobenzyl) piperazine; 1- (((4-methyl-2-oxo-2H-l-benzopyran-6-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,3-dibromo-4-formyl-6-methoxy-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) -perazine; 1- ((4- (2- (4-nitrophenyl) et-2-yl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2, 4, 6-tribromo-3-f ormilf enoxi) methyl) carbonyl -4- (4-chlorobenzyl) piperazine, -1- ((2-benzyl-4-chlorophenoxy) methyl) carbonyl (4 - chlorobenzyl) piperazine; 1- ((2- (bezothiazol-2-yl) phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-6-f luorofenoxi) met il) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-ethoxy-4-methyl phenoxy) 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) iperazine; 1- ((2- (piperidin-1-yl) phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine, -1- ((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-2H-l-benzopyran-7-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - ((2-methoxy-4-bromo-enoxy) -methyl) -carbonyl -4 - (4-chlorobenzyl) piperazine; 1- ((2-Chloro-4-bromo-6-methyl-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) -piperazine, -1- ((2,4-dimethyl-6-1-but-yl-enoxy)) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- (((2-nitro-4- (hydroxysulfonyl) naph talen-1-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- (((3- (hydroxysulfonyl) -6-aminonaf talen-1-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- (((3- (hydroxysulfonyl) -7-aminonaf such en-1-yl) oxy) ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - (((3- (methoxycarbonyl) naphthalen-2-yl) oxy) methyl) carbonyl- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-4- (hydroxysulfonyl) phenoxy) methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-n-butylcarbonylfluoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-ethoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; l- ((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) iperazine; 1- ((2, 4, 6-tribromo-3-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2-methoxy-5-yl-phenoxy) and il) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - ((3-methoxy-4-formylphenoxy) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine; 1- ((4- (2- (phenyl) et-2-enyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (1,2,4-triazol-1-yl) phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine, - 1- ((2-nitro-4-chloro-5-methyl) enoxi) 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; 1- ((2-methoxy -4- (2- (ethoxycarbonyl) ethyl) phenoxy) methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,3,4,6-Tetrachlorofenoxy) 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-chlorofenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-mercaptophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-6-f ormilf enoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2,4-di (1-methylbutyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-trifluoromethyl-4-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - ((2,6-dibromo-4- (methoxycarbonyl) phenoxy) methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4-dichloro-6-acetyl) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxycarbonyl-4-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-formyl-4-bromo-6-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2,6-diformyl-4-methylphenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine, -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-f-enyl-4 -oxo-4H-1-benzopyran-6-yl) oxy) methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-chloro-4-trif luoromethyl-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-3-met-il-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-methyl-1-quinolin-8-yl) oxy) -me il) -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) iperazine; l- ((2-amino-4- (1, 1-dimethylpropyl) phenoxy) -methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-difnyl-4-amino phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine, 1- (2-4-dichloro-3-methyl-6-aminofenoxyl) methyl ) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-oxo-4- (carboxy) met il-2H-1-benzopyran-7-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-oxo-4- trifluoromethyl-2H-1-benzopyran-7-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2-t-butyl-4-methoxy-phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, -1 - ((2-formyl-6-methyl-enoxy) -ethyl) -carbonyl-4 - ( 4-chlorobenzyl) piperazine, -1- ((2-methoxycarbonyl-4-acetyl-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2-bromo-5-f luorofenoxi) ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4-di (1,1-dimethylpropyl) phenoxy) ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-methyl-4-fluorophenoxy) methyl) carbonyl -4 - (4-chlorobenzyl) iperazine; 1- ((2,3-, 4-trifluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2,5-difluorofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1 - ((2-methyl-5-nitrofenoxi) methyl) carbonyl-4 - (4-chlorobenzyl) iperazine; 1- ((((2-methyl-3- (ethoxycarbonyl) indole-5-yl) oxy) ethyl) -carbonyl-4- (4-chlorobenzyl) piperazine, 1- ((2-aminocarbonyl-4-acetyl-enoxy)) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2,6-dinitro-3-t-butyl-yl-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-fluoro-4-nitro-enoxy) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine, -1- ((2-carboxy-3 -f luorofenoxi) methyl) carbonyl -4- (4- chlorobenzyl) piperazine; 1- ((2- (2-ethylhexoxy) carbonyl phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) iperazine; 1- ((2,4-, 6-tribromo-4-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1 - ((4 - (4-Bromofenyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, - 1 - ((4 - (4-carboxymethyl) phenoxy) methyl) carbonyl 4 - (4 -chlorobenzyl) iperazine; 1- ((2,3, 6-trifluorophenoxy) methyl) carbonyl-4 - (4-chlorobenzyl) iperazine; 1- ((2,4,5-trifluorophenoxy) methyl) carbonyl-4 - (4-chlorobenzyl) iperazine; 1- ((2,4-, 6-trifluorophenoxy) ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-Fluoro-5-trif luoromethyl-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazin-1 - (((2,4-dinitronaphthalen-1-yl) oxy) methyl) sarbonyl-4 - (4-chlorobenzyl) piperazine; 1 - (((3,6-di (hydroxysulfonyl) -8-aminonaphthalen-1-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-acetyl-4-chlorofenoxi) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine; 1- ((2,6-dimethyl-4- (1- (3,5-dimethyl-4-hydroxyphenyl) -1-methylethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (3 - (4-hydroxy phenyl) hex-2-yl) phenoxy) methyl) -carbonyl -4- (4-clprobenzyl) piperazine; 1- (((6- (hydroxysulfonyl) naphthalen-2-yl) oxy) -methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-Chloro-4-met-il-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) -piperazine, -1- ((2-bromo-4, 5 -dif luorofenoxi) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2-Chloro-4-methoxy-eoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4-chlorofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (2- (methoxycarboni) ethyl) f enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dif-enyl-4-nitro-enoxy) -yl) -carbonyl-4- (4-chlorobenzyl) piperazine, - 1- ((2-amino-3-methylfenoxy) methyl) carbonyl- 4- (4-chlorobenzyl) iperazine; 1 - ((2-methyl-4-fluorophenoxy) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine; 1 - . 1 - ((2-methyl-4-iodophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-fluoro-6-methoxy-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-3-isopropyl-6-methyl-yl-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) -perazine; 1- ((2-carboxy-3,4,6-trichloro-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-6-isopropyl-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (piperidin-1-yl) -4-methyl-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) -perazine; 1- (((2,3-dihydro-2, 2-dimethylbenzofuran-7-yl) oxy) -methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-di (t-buyl) -4- (1-methylpropyl) phenoxy) methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-methyl-4-bromo-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((phenanthren-9-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-4-bromo-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) -perazine; 1- ((2-f luoro-3-trif luoromethyl-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-5-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-chloro-4-aminofenoxi) me t il) carbonyl-4 - (4-chlorobenzyl) piperazine, -1- ((2-formyl-4-bromo-6-nitrophenoxy) methyl) carbonyl-4 - (4-chlorobenzyl) iperazine; 1- ((2-methoxy-4- (acetyl) methyl-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperaz ina, -1- ((4- (5-mercaptotetrazol-1-yl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4,6-Riyodo-3- (2-carboxy) bu-il-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) -piperazine; 1- ((3-hydroxymethyl-4-nitro-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; "1 - ((2, 3, 5, 6 -tetraf luoro- 4 - (2, 3, 4, 5, 6 -pentaf luorofenyl) fexy) methyl) carbonyl-4 - (4-chlorobenzyl) piperazine; - ((2 - (benzotriazol-2-yl) -4,6-di (1,1-dimethylpropyl) f enoxi) methyl) carbonyl-4- (4-chlorobenzyl) -piperazine; 1- ((2-f-enyl) -3-hydroxy-4-oxo-4H-1-benzopyran-6-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((indanonyl) oxy) methyl) carbonyl 4 - (4 -chlorobenzyl) iperazine; 1- ((2-nitro-4- (hydroxysulfonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-3-met-il-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (2, 4-dinitrophenyl) aminofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; l- ((3-methyl-4-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dibromo-4-nitro phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2,6-diiodo-4-nitro phenoxy) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine, -1 - ((2-formyl-4-nitro-enoxy) methyl) carbonyl-4- ( 4-chlorobenzyl) piperazine, -1 - ((2-atninofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - ((2-amino-5-nitrophenoxy) me il) carbonyl-4 - (4-chlorobenzyl) piperazine; 1 - ((2-amino-5-methyl phenoxy) methyl) carbonyl-4 - (4-chlorobenzyl) iperazine; 1- ((2-amino-4-chlorofenoxyl) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-amino-4-carboxy enoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-amino-4-t-butyl-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-amino-4-methyl-enoxy) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine, - 1- ((2-methyl-3-aminofenoxy) methyl) carbonyl -4- (4-chlorobenzyl) ) piperazine; 1- ((2-carboxy-5-aminofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-methyl-4-aminofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,5-dimethyl-4-amino phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2,6-dibromo-4-aminofenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - ((2-carboxy-4-aminofenoxi) me il) carbonyl -4- (4-chlorobenzyl) piperazine, 1- ((2-aminocarbonyl-f-enoxy) -me) -l) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-aminocarbonyl-4-chlorofenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; l- ((4- (2-aminoethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4,6-tri- (dimethylamino) phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2-hydroxymethyl-6-methoxy-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,3-dimethoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 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-methoxy-enoxy) -ethyl) -carbonyl-4- (4-chlorobenzyl) -perazine; 1- ((2-acetyl-4-me oxy pheno) i) il) carbonyl -4 - (4-chlorobenzyl) piperazine; 1- ((2-acetyl-3-methoxyphenoxy) ethyl) carbonyl -4 - (4-chlorobenzyl) piperazine; 1 - ((2-methoxy-4-acet-yl-enoxy) -methyl) -carbonyl -4 - (4-chlorobenzyl) -perazine; 1- ((2,6-dimethoxy-4-acet-yl-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((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; 1- ((3,5-di (t-butyl) phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1 - . 1 - ((2,6-di (isopropyl) phenoxy) ethyl) carbonyl -4 - (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4- (ethoxycarboni) methylphenoxy) -methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-ethoxy-5-prop-2-enyl-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) piperazine, -1- ((2-methoxy-5-prop-2-enyl-enoxy) -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-trif luoromethyl-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-cyclopentyl enoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-cyclopentylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,3-difluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-6-aminofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, 1- ((2-amino-4-chloro-5-nitrofenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, - 1- ((3,4-difluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-6-chlorofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4-dicarboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,3-dimethoxy-5-f ormilf enoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2-bromo-4-f luorof enoxi) met il) carbonyl-4- (4-chlorobenzyl) piperazine, -1- ((2,6-dichloro-4-f-luo-enoxy) ethyl) carbonyl-4 - (4-chlorobenzyl) piperazine; 1- ((3-methyl-4-isopropyl-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((fluoren-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - ((2-ethyl-ilaminofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2-amino-3-nitro-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-oxo-3,4, 8-trimethyl-2H-l-benzopyran-7-yl) oxy) methyl) carbonyl-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- (((1-Acetylnaphthalen-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, -l- ((2-methoxy-4-nitrophenoxy) methyl) carbonyl-4- (4- chlorobenzyl) piperazine; 1- ((3-methyl-5-isopropylphenoxy) methyl) carbonyl -4- (4-chlorobenzyl) iperazine; 1 - ((2-methyl-4-formylphenoxy) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine, 1- (((1-aminonaf-alen-2-yl) oxy) -yl) -carbonyl -4- ( 4-chlorobenzyl) piperazine; 1- ((4-Aminonaphthalen-1-yl) oxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy -4- (1,2-dihydroxyethyl phenoxy) methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((3- (2-aminoethyl) indolin-5-yl) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- (((5-chloroquinolin-8-yl) oxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4- (2- (amino) ethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 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-diaminofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, -1- ((2- (diethylamino) methyl-4-aminophenoxy) methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-me-il-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) iperazine; 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) -me il) carbonyl -4- (4-chlorobenzyl) piperazine, -1- ((2-carboxy-4-methyl-phenoxy) methyl) carbonyl-4- (4- chlorobenzyl) iperazine; 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-carboxyphenoxy) methyl) carbonyl-4- (4- chlorobenzyl) piperazine; 1 - ((4 - (2-carboxy) yl) phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2- (2-hydroxyethyl) phenoxy) methyl) carbonyl-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) iperazine; 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) carbonyl -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; l - ((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; 1- ((2-formyl-3,5-dimethoxyphenoxy) ethyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1 - ((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- (((f luoren-9-on-l-yl) oxy) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine; 1- (((4-hydroxy-l, 2,3,4-tetrahydronaphthalen-8-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,3,4,5,6-pentabromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 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-triiodophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1 - ((2-f or rmil-4-chloro phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((3-f ormilf enoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - (((l-bromonaf talen-2-yl) oxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine, 1- (((1,6-dibromonaphthalen-2-yl) oxy) methyl) carbonyl -4- (4-chlorobenzyl) iperazine; 1- (((l-nitrosonaf talen-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2,4-dichloronaphthalen-1-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-nitronaphthaien-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-methoxynaphthalen-1-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((1-formylnaphthalen-2-yl) oxy) methyl) carbonyl -4- (4-chlorobenzyl) iperazine; 1- (((1-carboxynaphthalen-1-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((L-amino-4- (hydroxysulfonyl) naph talen-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((4- (naphthalen-2-yl) aminophenoxy) ethyl) 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-hydroxymethyl phenoxy) methyl) carbonyl-4 - (4-chlorobenzyl) piperazine; 1- ((2- (hydroxymethyl) -4-bromofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, -1- ((2,6-di (hydroxymethyl) -4-methyl-enoxy) methyl) - carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2-methoxy -4- (hydroxymethyl) phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((4-mercaptophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-carboxyindol-5-yl) oxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine, 1- (((3-carboxy indol-5-yl) oxy) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine; 1- (((indol-4-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, 1- (((indol-5-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) ) piperazine; 1- ((2- (benzoxazol-2-yl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 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) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((5-Nitroquinolin-8-yl) oxy) -me il carbonyl -4- (4-chlorobenzyl) piperazine; 1- (((quinolin-5-yl) oxy) methyl) carbonyl-4- (4 - chlorobenzyl) piperazine, 1- (((5- (hydroxysulfonyl) -7-ydoquinolin-8-yl) oxy) -methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-phenyl-4) -oxo-4H-l-benzopyran-7-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; l - ((2-carboxy-2,5,7,8-e-ramethyl-2, 3 -dihydro-1-benzopyran-6-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- (((2-oxo-3-chloro-4-methyl-2H-l-benzopyran-7-yl) oxy) ethyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- (((2-OXO-3- (diethylamino) met yl) -4-methyl-2H-1-benzopyran-7-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-oxo-6-methoxy-2H-1-benzopyran-7-yl) oxy) methyl) -carbonyl- (4-chlorobenzyl) piperazine; 1- (((2-oxo-2H-l-benzopyran-7-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4-f ormil-6-bromofenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4-formyl-6-yodofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, -1- ((2-methoxy-4-f ormilf enoxy) methyl) carbonyl-4 - (4-chlorobenzyl) piperazine; 1- ((2-ethoxy-4-f ormilf enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-4-f ormilf enox) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2,4-dichloro-6-n-trofenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine, 1- (2,4-dinitro-6-f ormilf enoxy) methyl) carbonyl- 4- (4-chlorobenzyl) piperazine; < 1- ((2,4-dinitro-6-carboxy-f-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) piperazine, -1- ((2,4-dinitro -6-methyl-phenoxy) -methyl) -carbonyl- 4- (4-chlorobenzyl) iperazine; 1- ((2,5-dinitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-5-methylphenoxy) methyl) carbonyl-4 - (4-chlorobenzyl) iperazine; 1- ((2-nitro-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4-dinitrofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-4-f ormilf enoxi) met il) carbonyl-4- (4-chlorobenzyl) piperazine, -1- ((2-nitro-4-formyl-6-methoxy-enoxy) methyl) carbonyl- 4- (-chlorobenzyl) piperazine; 1- ((2-nitro-4-carboxy enoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-4-met-il-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dinitro-4-methyl phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) iperazine; 1- ((2-nitro-4- (carboxymethyl) phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; l- ((2", 6-dichlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - ((3-methoxy-5-chlorophenoxy) methyl) carbonyl -4 - (4-chlorobenzyl) iperazine; - ((4-cyanophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (1-methyl-l-phenylethyl) f enoxi) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((3- (ethylamino) -4-methyl-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) -piperazine, -1- (((2-acetyl-napht-en-1-yl) oxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2- (carboxymethyl) f enoxi) met il) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (carboxymethyl) f enoxi) met il) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((benzotriazol-1-yl) oxy) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine; 1- (((quinolin-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-f ormilf enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dimethoxy) -4- -f ormilf enoxi) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((3, 4-d imetoxif enoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4,6-tri (t-butyl) phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2,6-dimethoxy -4- (methoxycarbonyl) phenoxy) methyl) -carbonyl-4- (4-chlorobenzyl) iperazine; 1 - ((3-trif luor orne to i phenoxy) me il) carbonyl -4 - (4-chlorobenzyl) piperazine; 1- ((2-methyl-5-aminofenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (4-cyanofenyl) f enoxi) met il) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-nitro-4-aminofenoxi) met il) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-methyl phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) -piperazine; 1 - ((4-methyl-enox) -methyl) -carbonyl -4 - (4-chlorobenzyl) -piperazine, -1- ((4- (methoxycarbonyl) methyl-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) -piperazine; 1- (((carbazol-2-yl) oxymethyl) 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-4-oxo-4H-l-benzopyran-3-yl) oxy) -methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-oxo-4-methyl-2H-l-benzopyran-7-yl) oxy) methyl) -carbonyl -4 - (4-chlorobenzyl) piperazine, - 1- ((4-n) trofenoxy) methyl) carbonyl -4- (4-chlorobenzyl) -piperazine; 1- ((3-carboxy-4-aminofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2-methoxy) -5-aminofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((2-f eni 1-4-oxo -2, 3-dihydro-4H-1-benzopyran-6-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((quinolin-6-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2, 3-diaminofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (hydroxysulfonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, - 1- (((f-luorenon-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-tetrahydronaph so-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-cyano-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-f luorofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, -1- ((2,3,5, 6 -tet raf luorofenoxi) methyl) carbonyl -4- (4 -chlorobenzyl) piperazine, -1- ((2,6-difluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, -1- ((2,3-dichloro-enoxy) ethyl) carbonyl-4- (4 - chlorobenzyl) iperazine; 1- ((2, 3, 6-trichlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-chloro-4,5-dimethyl phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2,5-dichlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2-Chloro-5-methylfenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, -1- ((2- (methylcarbonyl) aminofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) ) iperazine; 1- ((2-isopropoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - 1 - ((2 - (benzyloxy) phenoxy) met yl) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - ((2-ethoxy-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1 - ((2-f-enylf-enoxy) -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 - . 1 - ((2-acetyl-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (ethylcarbonyl) f enoxi) met il) carbonyl-4- (4-chlorobenzyl) piperazine, -l- ((2- (t-butyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) ) piperazine, - 1- ((2-isopropyl-enoxy) 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) iperazine; 1- ((2, 3, 5-trimethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - ((2, 3, 6-trimethyl-ilphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2,4-dimethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2,4-, 6-trimethoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methyl-5-isopropyl-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,5-dimethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, -1 - ((2,5-dimethyl-4- (diethylamino) methylphenoxy) -methyl) carbonyl-4- ( 4-chlorobenzyl) piperazine; 1- ((2- (t-butyl) -6-methylfenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1 - ((2,6-Dimethoxy-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) -perazine; 1- ((2-prop-3-enyl-6-met-il-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, -1- ((2-prop-2-enylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-ethyl) enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-n-propylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; l- ((3-fluorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3,5-difluorofenoxi) methyl) carbonyl (4-chlorobenzyl) piperazine; 1- ((3-Chloro-4-f luorofenoxyl) ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3,5-dichlorophenoxy) methyl) carbanyl-4- (4-chlorobenzyl) piperazine; 1- ((3-Iodophenoxy) methyl) carbonii-4- (4-chlorobenzyl) piperazine; 1- ((3- (phenylamino) f enoxi) me useful) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((3- (diethylamino) f-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) piperazine, - l - ((3-f-enyl-f-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) -perazine; 1- ((3-acetyl-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) -perazine; 1- ((3-trifluoromethyl-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-t-butylphenoxy) methy1) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((3-isopropylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - ((3-methyl-4-acetyl-enoxy) -ethyl) -carbonyl-4- (4-chlorobenzyl) piperazine, 1- ((3,4-dimethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) -perazine; 1- ((2-t-butyl-5-methylphonoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-isopropyl-5-methyl-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-ethyl) enoxy) methyl) carbonyl-4 - (4-chlorobenzyl) piperazine; 1- ((2,6-dimethyl-4-bromo-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dibromo-4-f luorofenoxi) methyl) carbonyl -4- (4-chlorobenzyl) iperazine; 1 - ((2-bromo-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2-methyl-4-chlorophenoxy) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine; 1- ((2-isopropyl-4-chloro-5-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((4- (methylcarbonyl) aminofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - ((4-ethoxy-enoxy) 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; 1- ((4-n-hexoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((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) piper zine, -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-yl yl yl yl) phenoxy) me il) carbonyl- 4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-4-methylfenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-acetyl-4-methylphenox i) useful) carbon il-4- (4-chlorobenzyl) iperazine; 1- ((2- (t-butyl) -4-met il-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3- (ethylamino) -4-methyl-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, -1- ((4- (methoxycarbonyl) methyl-enoxy) -methyl) -carbonyl -4- (4- chlorobenzyl) piperazine, - 1 - ((4-ethyl) enoxy) methyl) carbonyl -4 - (4-chlorobenzyl) iperazine; 1- ((4-n-propylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((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-diiodophenoxy) methyl) carbonyl-4- (4 -chlorobenzyl) iperazine; 1- ((2-carboxy-6-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - ((2-carboxy-6-methyl-phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-5-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - ((2-carboxy-5-methoxyphenoxy) methyl) carbonyl- (4-chlorobenzyl) piperazine; 1 - ((2-carboxy-5-methyl-phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-4-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-carboxy-4-fluorophenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine, -1 - ((2-carboxy-4-chlorophenoxy) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine; 1- ((2-carboxy-4-dodophenoxy) met yl) carbonyl-4- (4-chlorobenzyl) piperazine, -1- ((2-carboxy-4-methoxy-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) ) piperazine; 1 - ((2-chloro-enoxy) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine; 1- ((2, 3,4-trichlorophenoxy) methyl) c-rbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,3,4,5, 6-pentachloro-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4,5-trichlorophenoxy) methyl) carbonyl-4 - (4-chlorobenzyl) piperazine, 1- ((3-methoxy-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3- (methoxycarbonyl) phenoxy) ethyl) carbonyl-4- (4-chlorobenzyl) piperazine, -1 - ((3 - (ethoxycarbonyl) phenoxy) ethyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((4-bromo-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2,6-dimethyl-4-bromo-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3,5-dimethyl-4-bromo phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-methyl-4-chlorophenoxy) me il) c-rbonyl-4 - (4-chlorobenzyl) piperazine, -1- ((2-isopropyl-4-chloro-5-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-ethoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (t-butyl) -4-methyl-enoxy) -ethyl) -carbonyl-4- (4-chlorobenzyl) -piperazine, -1- ((3-formyl-4-nitro-enoxy) -methyl) -carbonyl-4 - (4-chlorobenzyl) piperazine, - 1- ((2-methoxy-4-prop-3-enylf-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (1-phenylethyl) -4-chloro-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (ethoxycarbonyl) methyl phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; "1 - ((4-trifluoromethoxifenoxi) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine; 1- ((3-fluoro-4-chlorophenoxy) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine, - 1- ((2-fluoro-4-chloro-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, - 1- (((7-methoxynaphtalen-2-yl) oxy) methyl) carbonyl -4- ( 4-chlorobenzyl) piperazine; 1- ((2-benzyloxy-4-cyano-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; l- ((2-chloro-3,5-dimethoxy phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2-bromo-3,5-dimethoxy phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((3,5-dimethoxy-4-bromo-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-dibromo-3,5-dimethoxy phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1 - ((4-chloro-enoxy-methyl) -carbonyl-4- (4-chlorobenzyl) -piperazine; 1 - ((3-nitro-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) -piperazine; methyl-3-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3,5-dimethoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (2-nitro) 3-carboxy-6-methyl-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1 - ((3-cyano-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) piperazine, - 1 - ((2 -methoxy-5-nitrophenoxy) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine, 1- ((2-nitro-5-carboxy-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3- (carboxymethyl) f enoxy) met il) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-5-carboxy-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (dimethylamino) methylf-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (2- (dimethylamino) ethylf-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-carboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - (((naphthalen-1-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- (((5-aminonaphthalen-1-yl) oxy) methyl) carbonyl-4- (4- chlorobenzyl) piperazine, 1- ((3-nitro-4-aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,6-di (t-butyl) -4-methyl) enoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-carboxy-4-nitro-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2-methyl-5) -carboxyloxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-4-aminofenoxyl) me il) carbonyl-4 - (4-chlorobenzyl) piperazine; 1- ((4- (benzyloxy) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4 - (aminocarbonyl) phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((3,5-di (trifluoromethyl) f enoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4-dibromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2,6-dibromo-4-methylfenoxy) ethyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2,4-dichlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-methoxy-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) -piperazine; 1- ((3,5-dimethyl-4-bromo-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3,5-dicarboxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-Chloro-4-carboxy phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine, 1- (2,6-dichloro-4-carboxy-enoxy) methyl) carbonyl -4- (4-chlorobenzyl) iperazine; 1- (((2-carboxyquinolin-4-yl) oxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2,6-dimethyl-4-formylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2,6-di (t-butyl) -4-carboxyphenoxy) ethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-amino-5-carboxyphenoxy) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine; 1- ((2,6-di (t-butyl) -4- (hydroxymethyl) phenoxy) methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((4-carboxyquinolin-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-nitro-4-chlorophenoxy) methyl) carbonyl-4 - (4-chlorobenzyl) iperazine; 1- ((3-ethyl-4-chloro-5-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 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) met il) carbonyl -4- (4-chlorobenzyl) piperazine, -1- ((2-chloro-4-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-trif luromet ilf enoxi) met il) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methylphenyl) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methyl-4-acetyl-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, -1 - ((3 - (dimethylamino) phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((3-methyl-4-acetyl phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((3,5-dimethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-f-enylf-enoxy) -methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (ethoxycarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; l- ((4-Acetylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, -1- ((4-benzyl-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, - 1- ((2 -methoxy -4 -carb oxi phenoxy) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine; 1- (((3-carboxinef talen-2-yl) oxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2- (hydroxymethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- (((quinolin-8-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, 1- ((3-aminophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, -1 - ((4- (aminocarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((3,5-dimethoxy-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (cyclohexyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((quinolin-6-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, 1- (2-4-chloro-3-methylphenyl) methyl) -4-carbonyl - (4-chlorobenzyl) piperazine; l- ((2,5-dimethylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-bromophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3- (methylcarbonyl) aminofenoxi) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((3-acetylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-trifluoromethyl-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - . 1 - ((4-bromofenoxyl) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2-f ormilf enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-5-f ormilf enoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((tropinon-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-5-f luorofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-5- f ormilf enoxi) methyl) carbonyl -4 - (4-chlorobenzyl) piperaz ina, - 1 - ((3-formyl-4-nitro-enoxy) me il) car onyl -4 - (4-chlorobenzyl) piperazine; 1- ((2-carboxy-5-nitro-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1 - ((2-amino-4-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-amino-3-carb oxy phenoxy) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-4-aminofenoxi) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2,6-dichloro-4-nitro-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3-fluoro-4-nitrophenoxy) methyl) carbonyl -4 - (4-chlorobenzyl) piperazine, 1- ((2,3-difluoro-6-nitro-enoxy) methyl) carbonyl -4- ( 4-chlorobenzyl) piperazine; l - ((2-chloro-4-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-nitro-4-cyano-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-bromo-4-methyl-enoxy) -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 - ((3,4,5- t rime t yl phenoxy) met il) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-f luorofenoxylethyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3,5-dimethyl-4-chloro-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; - ((4-methoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4- (methoxycarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, - 1 - ((4-trif luoromethyl) enoxi) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; l- ((4-t-butylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-isopropylphenoxy) methyl) -carbonyl-4- (4-chlorobenzyl) piperazine; 1- (((naphthalen-2-yl) oxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, 1- (((6-bromonaf-alen-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-nitro-enoxi) methyl) carbonyl -4- (4-chlorobenzyl) piperazine; 1 - ((2-nitro-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy -4- (amino) methylf-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3- (aminocarbonyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, 1- ((3- (methoxycarbonyl) methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (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-fluorobenzyl) piperazine, - 1- ((2- (4- (methyl) phenylcarbonyl) -5-methoxyphenoxy) -methyl) carbonyl-4- (4-fluorobenzyl) piperazine; 1- ((2-phenylcarbonyl-5-octoxyphenoxy) methyl) carbonyl-4- (4-fluorobenzyl) piperazine; l- ((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-fluorobenzyl) piperazine; 1- ((2-methoxy -4- (3-hydroxyprop-2-enyl) phenoxy) methyl) -carbonyl-4- (4-fluorobenzyl) iperazine; (((3- (phenylaminocarbonyl) naphthalen-2-yl) oxy) -methyl) carbonyl-4- (4-fluorobenzyl) piperazine; 1- (((6- (phenylcarbonyl) naphthalen-2-yl) oxy) methyl) -carbonyl-4- (4-f luorobenzyl) piperazine; 1- ((2- ((2-phenylethyl) carbonyl) phenoxy) methyl) carbonyl-4- (4-fluorobenzyl) piperazine, - 1- ((4- ((4-f luorofenyl) carbonyl) phenoxy) methyl) carbonyl-4 '(4-f luorobenzyl) piperazine, -1- ((2- (phenylamino) carbonylf enoxy) methyl) carbonyl -4- (4-f luorobenzyl) piperazine; 1 - ((2-f-enylcarbonyl-f-ene) methyl) carbonyl-4 - (4-fluorobenzyl) piperazine; 1- ((2-f-enylcarbonyl-4-chloro-5-methyl-enoxy) -methyl) -carbonyl-4- (4-f-luorobenzyl) -perazine; 1- ((4- (4-chlorophenyl) carbonylf enoxy) methyl) carbonyl-4- (4-f luorobenzyl) piperazine; 1- ((4-benzylcarbonyl) phenoxy) methyl) carbonyl-4- (4-f luorobenzyl) iperazine; 1- ((2-f-enylcarbonyl-4-methyl-yl-enoxy) -methyl) -carbonyl -4- (4-f-luorobenzyl) piperazine; 1- ((4- (2-methylcarbonylethyl) phenoxy) methyl) carbonyl-4- (4-fluorobenzyl) piperazine; 1- ((4-phenylcarbonyl-enoxy) -methyl) -carbonyl-4- (4-f-luorobenzyl) piperazine; and 1 - ((3-f-enylcarbonyl phenoxy) methyl) carbonyl-4 - (4-fluorobenzyl) piperazine, - D. In a similar manner, other compounds of the formulas (la), (Ib), (le) are prepared and (Id).

EXAMPLE 3 Compounds of formula (la) and formula (Ib) A. To a solution of 1- (3, 4, 5-trimethoxyphenoxy) methylcarbonylpiperazine (0.22 g, 0.70 mmol) in 1% acetic acid in methanol (6 mL) is added 4-cyanobenzaldehyde (0.33 g, 2.5 mmol) and sodium cyanoborohydride (0.093 g, 1.4 mmol). The resulting mixture is stirred at room temperature for 1.5 hours and the mixture is then concentrated from the volatile fractions in vacuo. The residue is taken up in ethyl acetate and washed with a saturated aqueous solution of NaHCO 3, water and then brine. The organic layer is separated, dried over MgSO4, filtered and concentrated in vacuo to give a yellow oil. Purification by flash column chromatography on silica gel provides 0.21 g of 1- (3,4,5-trimethoxyphenoxy) methyl) carbonyl-4- (4-cyanobenzyl) piperazine, a compound of formula (Ib), as an oil Transparent: NMR (CDC13) 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. In a similar manner, other compounds of formula (Ib) are prepared: 1- ((3,4,5-trimethoxy phenoxy) rae tyl) carbonyl -4- (3,4-dimethoxybenzyl) piperazine; 1- ((3, 4, 5-t rime tox i phenoxy) methyl) carbonyl-4- (4-methoxybenzyl) piperazine; 1 - ((3, 4, 5-trimethoxy phenoxy) methyl) carbonyl-4- (3-chlorobenzyl) piperazine; 1- ((3,4,5-trimethoxy phenoxy) methyl) carbonyl-4- (3-trifluoromethylbenzyl) piperazine, - 1- ((3,4,5-trimethoxy phenoxy) methyl) carbonyl -4- (2, 3-dimethyl-4-methoxybenzyl) piperazine, -1- ((3, 4, 5-trimethoxy phenoxy) methyl) carbonyl-4- (3-f-enoxybenzyl) piperazine; 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl -4 - (4 - (dimethylamino) benzyl) piperazine, - 1- ((3,4,5-trimethoxy phenoxy) methyl) carbonyl -4 - (4 - (methylthio) benzyl) piperazine; 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl -4- (4-methoxy-3-methylbenzyl) iperazine; 1- ((3,4,5-trimethoxy phenoxy) methyl) carbonyl-4- (2-chlorobenzyl) piperazine; 1 - ((3,4,5- t rime tox i phenoxy) me il) carbonyl -4 - (3-nitrobenzyl) piperazine; 1- ((3, 4, 5-trimethoxy-enoxy) methyl) carbonyl-4- (4-hydroxybenzyl) piperazine; 1- ((3, 4, 5-trimethoxy-enoxo) methyl) carbonyl-4- (3,5-dibromo-4-hydroxybenzyl) piperazine; 1- ((3, 4, 5-trimethoxy-enoxy) methyl) carbonyl-4- (2-f-luorobenzyl) piperazine; 1- ((3,4,5-trimethoxy-enoxo) methyl) carbonyl-4- (4-f-luorobenzyl) piperazine; NMR (CDC13) 7.3 (, 2), 7. 0 (m, 2), 6.2 (s, 2), 4.6 (s, 2), 3.9 (m, 9), 3.6 (m, 4), 3.4 (s) , 2), 2.4 (m, 4) ppm; 1 - ((3,4,5-trime oxy eno) ethyl) carbonyl-4 - (4-bromobenzDpjperazine; 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-trimethoxy-enoxo) methyl) carbonyl-4- (2-bromobenzyl) piperazine; 1- ((3,4,5-trimethoxy-noxy) methyl) carbonyl-4- (3-f-luorobenzyl) -perazine; 1- ((3,4,5-rime oxifenoxi) me il) carbonyl-4- (3-bromobenzyl) piperazin; 1- ((3,4,5-trimethoxy-enoxo) methyl) carbonyl-4- (3-cyanobenzyl) piperazine; l- ((3_, 4, 5-trimethoxy-enoxy) methyl) carbonyl-4- (2,4-difluorobenzyl) piperazine; 1- ((3,4,5-trimethoxy-enoxo) methyl) carbonyl-4- (2,3-difluorobenzyl) piperazine; 1- ((3,4,5-trimethoxy-enoxo) methyl) carbonyl-4- (3,4-difluorobenzyl) piperazine; NMR (CDC13) 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-trimethoxy-enoxi) 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-f luorobenzyl) piperazine, -1 - ((3, 4, 5-trimethoxy-enoxy) -methyl) -carbonyl-4 - (4-trifluoromethylbenzyl) piperazine; 1 - ((3,4,5-trimetho if ene i) met il) carbonyl-4 - (4-nitrobenzyl) piperazine; 1- ((3,4,5-trimethoxy-enoxy) -methyl) -carbonyl-4- (4-fluorobenzyl) -perazine; 1- ((3,4,5-trimethoxy-enoxi) methyl) carbonyl-4- (2,5-difluorobenzyl) iperazine; 1- ((3,4,5-trimethoxy-enoxy) methyl) carbonyl-4- (3-nitro-4-hydroxybenzyl) piperazine; 1 - . 1 - ((4-chloro-enoxy) methyl) carbonyl -4 - (4-f-luorobenzyl) piperazine; NMR (CDC13) 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 - ((4-chloro-enoxy) methyl) carbonyl -4 - (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-trimethoxy-enoxo) methyl) carbonyl-4 - (3 - (benzyloxy) benzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-4- (3,4,5-trimethoxybenzyl) piperazine, - C. In a similar manner, the following compounds of formula (la) are prepared: (3S) -1- ((4-chloro phenoxy) methyl) carbonyl-3-methyl-4- (4-f luorobenzyl) 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), 2.7 (m, 1), 2.5 (m, 1), 2.1 (, 1), 1.1 (m, 3) ppm; (3R) -1- ((4-chloro phenoxy) 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) carbonyl-3- (2- ((((4-c-lor phenoxy) methyl) carbonyl) oxy) ethyl) -4- (4-fluorobenzyl) -piperazine; 1- ((4-chlorofenoxyl) methyl) carbonyl-2-hydroxyethyl-4- (4-fluorobenzyl) piperazine, 1- ((4-chlorophenoxy) methyl) carbonyl-2- (2- (2 -methylpropyl) amino) ethyl) -4- (4-f luorobenzyl) piperazine; NMR (CDC13) 7.1 (m, 4), 6.9 (t, 2), 6.7 (d, 2), 4.6 (s, 2), 4.4 (d, l), 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; 1- ((4-chlorofenoxyl) methyl) carbonyl-2- (2- ((4-f luorobenzyl) amino) ethyl) -4- (4-f luorobenzyl) piperazine hydrochloride salt; 1- ((4-chlorophenoxy) methyl) carbonyl-2- (2- ((2-hydroxyethyl) amino) ethyl) -4- (4-f luorobenzyl) iperazine; 1 - ((4-chlorofenoxylmethyl) carbonyl -2 - (2 - ((methyl) amino) ethyl) -4- (4-fluorobenzyl) piperazine; hydrochloride salt of 1- ((4-chlorofenoxi) methyl) carbonyl -3- (2- ((4-fluorobenzyl) amino) ethyl) -4- (4-f luorobenzyl) piperazine; 1- ((4-chlorofenoxi) methyl) carbonyl -3- (2- ((methyl) amino ) -ethyl) -4- (4-f luorobenzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-3- (2- ((2-hydroxyethyl) amino) ethyl) -4- (4-f luorobenzyl) ) piperazine; l- ((4-chlorophenoxy) methyl) carbonyl-3- (2- ((2-methylpropyl) amino) ethyl) -4- (4-f luorobenzyl) piperazine; (trans) -1- ((4 -chloro-2- (((ethyl) amino) methyl) -phenoxy) -methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) iperazine; (CDC13) 7.3 (m, 4), 7.0 (d.2), 6.9 (t, 1), 6.4 (s broad, 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 (broad 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, 4), 3.2 (m, 1), 3.0 (m, 1), 2.7 (dd, 1), 2.6 (c, 2), 2.2 (d, 1), 1.3 (m, 3), 1.0 (m, 9) PPm; (trans) -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 (s broad, 1) 2.7 (d, 1), 2.2 (m, 2), 1.3 (m, 3), 0.9 (m, 3), 0.5 (m, 4) ppm; (trans) -1- ((4-chloro-2- (((dimethyl) -amino) -yl) -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, 3), 4.1 (m, 1), 3.6-3.4 ( m, 4), 3.0 (broad 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-f luorobenzyl) piperazine; NMR (CDC13) 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 (broad 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) -me yl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; 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 (broad s, 1), 2.7 (dt, 1), 2.2 (d, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- ((4-methylpiperazin-1-yl) methyl) -phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 4), 7.1 (dd, 1), 7.0 (t, 2), 6.8 (d, 1), 4.7 (m, 4), 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; (trans) -1- ((4-chloro-2- ((piperazin-1-yl) methyl) -phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-dg) 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 (CDC13) 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 (s broad, 2), 2.7 (m, 4), 2.2 (d.2), 1.3 (m, 3), 0.9 (m, 3) ppm; (trans) -1- ((4-chloro-2- ((morpholin-4-yl) methyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-fluorophenyl) 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 (broad 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) piperazine; 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 (c, 2), 3.0 (m, 1), 2.7 (m, 3), 2. 6 (c, 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 (DMS0-ds) 7.9 (m, 1), 7.7 (m, 2), 7.5 (m, 1), 7.2 (m, 3), 5.1 (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-f luorobenzyl) 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-dg) 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 (m, g), 0.9 (d, 6) ppm; (trans) -1- ((4-chloro-2- ((cyclopropylmethyl) aminomethyl) -phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 3), 7.1 (dd, 1), 7.0 (t, 2), 6.8 (broad d 1), 4.7 (m, 2), 3.8 (s, 2), 3.6 (m, 1), 3.5 (c, 2), 3. 0 (m 2), 2. 7 (dd, 1), 2.4 (m, 3), 2.2 (d, 1) 1.3 (m, 3), 0.9 (m, 4), 0.4 (m, 2), 0.1 (m, 2) ppm; (trans) -1- ((4-chloro-2- (phenylaminomethyl) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; NMR (DMSO-ds) 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 (m, 2), 3.9-3.4 (, 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 (broad d 1), 4.6 (broad s, 3), 4.0 (m , 2), 3.6 (d, 1), 3.4 (d, 1), 3.0 (m, 1), 2.7 (dd, 1), 2.5 (dc, 1), 2.4 (dc, 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) iperazine; NMR (CD30D) 7.6 (, 3), 7.5 (d, 1), 7.3 (m, 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 (m, 3) ppm; (2R) -1- ((4-Chloro-2- ((4-t-butoxycarbonylpiperazin-1-yl) methyl) phenoxy) -yl) -carbonyl-2-methyl-4- (4-fluorobenzyl) -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-t-butoxycarbonylpiperazin-1-yl) methyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMS0-d6) 7.8 (m, 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 (broad 1), 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 (c d, 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; and D. In a similar manner, the following compounds of formula (Id) are made; 1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4 - (2-brombthienyl) methylpiperazine; NMR (CDC13) 7.2 (d.2), 6.8 (dd, 3), 6. 6 (d, 1), 4.6 (s, 2), 3.6 (s, 4), 3.5 (t, 2), 2.4 (c, 4) ppm. E. In a similar manner, other compounds of formulas (la), (Ib), (le) and (Id) are prepared.

EXAMPLE 4 Compounds of formula (la) A. To a solution of (2R, 5R) -1 - ((4-chloro-enoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5 - ((hydroxy) methyl) piperazine (0.17 g, 0.42 mmol ) in CH2C12 (50 ml) at 0 ° C is added triethylamine (excess) and methanesulfonyl chloride (0.050 ml, 0.5 mmol). The resulting mixture is stirred at 0 ° C until alcohol consumption is observed by CCD analysis. The mixture is concentrated from the volatile fractions in vacuo. The residue is taken up in anhydrous DMF (5 ml) and K2CO3 (excess) is added, followed by tetrazole (0.050 g, 0.71 mmol). The resulting mixture is stirred at room temperature for 3 days and filtered. The filtrate is concentrated in vacuo and the residue is taken up in ethyl acetate. This is washed with water, then with brine and then dried over MgSO4 and concentrated in vacuo to give a yellow oil. Purification by flash column chromatography on silica gel provides 25 mg of (2R, 5R) -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 a similar manner, the following compounds of formula (la) are prepared: (2R, 5R) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((1, 2,4-triazol-2-yl) methyl) piperazine; NMR (CDC13) 7. 9 (s, 1), 7.3 (m, 5), 6.9 (m, 4), 4.7 (m, 3), 4.4-3.4 (m, 5), 3.1-2.7 (, 2), 2.4 (t, 1 ), 2.0 (d, 1), 1.2 (m, 3) ppm; (2R, 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 (m, 3), 2.3 (m, 2), 2.0 (m, 1), 1.2 (m, 3) ppm; (2R, 5R) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((piperazin-lyl) methyl) piperazine; (2R, 5S) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((diethylamino) 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), 2.8-2.3 (m, 7), 1.2 (m, 3), 0.9 (t, 6) ppm; (2R, 5S) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- (((ethyl) mino) methyl) piperazine; NMR (CDC13) 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; (2R, 5S) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((4-methyl-piperazin-1-yl) methyl) iperazine; 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- (t-butoxycarbonyl) -piperazin-1-yl) ethyl) piperazine hydrochloride salt; (2R, 5S) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((dimethylamino) methyl) piperazine; (2R, 5S) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- (((cyclopropyl) amino) methyl) -piperazine; (2R, 5S) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) -5- ((cyano) methyl) piperazine; NMR (CDC13) 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, 5S) -1- ((4-chlorofenoxi) methyl) carbonyl-2-methyl-4- (4-f luorobenzyl) - 5- ((((cyclopropyl) methyl) amino) methyl) -piperazine; (2R, 5R) -1- ((4-chloro-enoxy) methyl) carbonyl-2-methyl-4-f-luorobenzyl) -5- (((2-hydroxyethyl) thio) methyl) piperazine; NMR (CDC13) 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- ((-chloro-2- (imidazol-1-ylmethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; NMR (DMSO-dg) 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) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) -piperazine; NMR (CDC13) 7.6 (s, 1), 7.3 (, 2), 7.2 (dd, 1), 7.0 (, 5), 6.8 (d, 1), 5.8 (c, 1), 4.6 (m, 3) , 4.2 (m, 1), 3.5 (c, 2), 3. 2 (m, 1), 3.0 (m, 1), 2.7 (dd, 1), 2.2 (dd, 1), 2.0 (s broad, 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 (c, 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-f luorobenzyl) piperazine; NMR (CDCl 3) 9.4 (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 (c, 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. C. In a similar manner, other compounds of formulas (la), (Ib), (le) and (Id) are prepared.

EXAMPLE 5 Compounds of formula (la) A. To a solution of oxalyl chloride (0.62 g, 5 mmol) in CH2C12 (20 mL) at -50 ° C is added DMSO (0.85 g, 11 mmol in 5 mL solution of CH2C12) for 2 minutes. It is added 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxyethyl) piperazine (1.85 g, 4.5 mmol, in 5 ml solution of CH2C12). The resulting mixture is stirred at -50 ° C for 15 minutes, and then triethylamine (2.3 g, 22 mmol) is added.

After 5 minutes at -50 ° C, the mixture is gradually heated to room temperature. At this time, the mixture is diluted with CH2C12 and washed with water and then with brine. The organic layer is then dried over MgSO4 and concentrated in vacuo to provide 1.7 g of 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- ((formyl) methyl) piperazine as an oil. yellow; NMR (CDCl 3) 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. In a similar manner, the following compounds of formula (la) are made: 4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) -methyl) carbonyl-3- ((acetyl) methyl hydrochloride salt) piperazine; NMR (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 (2R, 5S) -4- (4-fluorobenzyl) -1 - ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5-formylpiperazine. C. In a similar manner, other compounds of formulas (la), (Ib), (le), and (Id) are prepared. "" "EXAMPLE 6 Compounds of formula (la) A. To a solution of 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- ((formyl) methyl) piperazine (0.31 g, 0.77 mmol) in anhydrous THF (20 ml) was added. add methylmagnesium bromide (0.26 ml, 0.77 mmol, 3.0 M solution in ether). The resulting mixture is stirred overnight at room temperature. At this time, the mixture is poured into a 5% aqueous solution of NH 4 Cl and extracted with two portions of ether. The combined organic extracts are washed with brine, and then dried over MgSO4, filtered and concentrated in vacuo to give a yellow oil. Purification by flash column chromatography on silica gel provides 0.29 g of 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxypropyl) piperazine, as a clear, colorless oil, which is converted to its hydrochloride salt; NMR (CDC13) 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. In a similar manner, compounds of formula (la) are prepared: 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxy-2-phenylethyl) piperazine; NMR (CDCl 3) 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- ((4-chloro-enoxy) methyl) carbonyl-3- (2-hydroxypentyl) piperazine; NMR (CDCl 3) 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- (4-fluorobenzyl) -1- ((4-chloro-enoxy) methyl) carbonyl-3- (2-hydroxy-4-enyl) iperazine; NMR (CDCl 3) 7.3 (m, 4), 7.0 (t, 2), 6.8 (d, 2), 5.7 (m, 5.2 (dd, 1), 5.1 (t, 1), 4 5 (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-chlorof enoxi) methyl) carbonyl-3- (2-hydroxy-2- (4-methylphenyl) ethyl) piperazine; hydrochloride salt of (2R, 5R) -4- (4-f luorobenzyl) -1- ((4-chlorophenoxy) ) methyl) carbonyl -2-methyl-5 - (l-hydroxyprop-2-enyl) piperazine; NMR (DMSO-d6) 10.1 (broad 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; (2R, 5R) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5 - (1- hydrochloride salt hydroxybutyl) piperazine, - NMR (DMSO-dg) 10.3 (broad s, 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, ), 1.4 (m, 4), 1.1 (d, 3), 0.8 (t, 3) ppm; 4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxybut-4-ynyl) piperazine, -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxy-2-cyclohexylethyl) -piperazine; (2R, 5R) -4- (4-Fluorobenzyl) -1 - ((4-chlorophenoxy) me il) -carbonyl-2-yl-5- (lhydroxy-yl) piperazine hydrochloride salt; NMR (DMSO-dg) 10.3 (broad s, 1), 7.6 (m, 2), 7.3 (m, 4), 6.9 (d.2), 5.6 (broad s, 1), 4.9 (m, 2), 4.6-4.0 (m, 6), 3.2 (m, 3), 1.2 (d, 3), 1.1 (d, 3) ppm; (2R, 5R) -4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-5- (1-hydroxy-1- (phenyl) methyl) piperazine hydrochloride, - 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) iperazine; 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 (broad m, 3). 0.9 (broad m, 3) ppm; 1- ((4-chlorophenoxy) methyl) carbonyl-2- (1-hydroxyethyl) -4- (4-fluorobenzyl) iperazine; NMR (CDCl 3) 7.2 (m, 4), 7.0 (m, 2), 6.8 (dd, -2), 4.7 (, 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; 1- ((4-chlorophenoxy) methyl) carbonyl-2- (2-hydroxypropyl) -4- (4-fluorobenzyl) piperazine; NMR (DMSO-ds) 7.6 (broad s, 2), 7.3 (d, 4), 6.9 (c, 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) methyl) carbonyl-2- (2-hydroxybut-3-enyl) -4- (4-fluorobenzyl) piperazine; NMR (DMSO-dg) 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. C. In a similar manner, other compounds of formulas (la), (Ib), (le) and (Id) are prepared.

EXAMPLE 7 Compounds of formula (la) 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) is added sodium hydride (0.006 g, 0.15 mmol). The resulting mixture is stirred at room temperature for 30 minutes, and then methyl iodide (0.016 g, 0.11 mmol) is added. Once the analysis by thin layer chromatography shows that the complete consumption of 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (2-hydroxy-2-) has been carried out. phenylethyl) piperazine, the mixture is poured into water and extracted with two portions of ether. The combined organic extracts are dried over MgSO4, filtered and concentrated in vacuo to provide 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, 1), 2.9 (s, 1), 2.6 (m, 1), 2.4 (m, 1), 1.9 (m, 1) ppm. B. In a similar manner, other compounds of the invention are prepared: (2R, 5R) -4 - (4-fluorobenzyl) -l- ((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 (broad s, 1), 2.7 (dd, 1), 2.3 (t, 1), 1.2 (m, 3) ppm; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (2- (methoxy) ethyl) iperazine; NMR (CDC13) 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 (m, 6), 2.8 (m, 3), 2.0 (m, 4) ppm; 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3- (ethoxycarbonyl) methylpiperazin-2-one, 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-piperazin-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-f luorobenzyl) -1- ((4-chloro-enoxy) 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-chloro-enoxy) ethyl) -piperaz-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-f luorobenzyl) -1 - (2- (4-chlorophenoxy) ethyl) -3- ((ethoxycarbonyl) methyl) piperazin-2-one hydrochloride salt; NMR (CDCI3) 7.2 (m, 2), 7.1 (m, 4), 6.8 (d, 2), 4.2 (m, 9), 3.5 (m, 5), 2.9 (broad s, 1), 1.3 (t , 3) ppm; (trans) -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 (broad m, 2.5), 4.2 (broad s, 0.5), 3.8 (s, 3), 3.6-3.2 (m, 4 ), 3.0 (broad s, 1), 2.7 (m, 1), 2.2 (d.1), 1.2 (broad m, 3), 1.9 (broad m, 3) ppm; and (trans) -1- ((5-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 (broad m, 2.5), 4.2 (broad s, 0.5), 3.8 (s, 3), 3.6-3.2 (m, 4 ), 3.0 (broad s, 1), 2.7 (m, 1), 2.2 (d, 1), 1.2 (broad m, 3), 1.9 (broad m, 3) ppm. C. In a similar manner, other compounds of formulas (la), (Ib), (le) and (Id) are prepared.

EXAMPLE 8 Compounds of formula (la) A. To a solution of 4-chlorobenzyl isocyanate (0.59 g, 3.5 mmol) in anhydrous THF (15 ml) at 0 ° C is added 1- (4-chlorobenzyl) piperazine (0.74 g, 3.5 mmol). The resulting mixture is stirred at room temperature. After 20 hours, the mixture is concentrated from the volatile fractions. The resulting solid is washed with ethyl acetate and dried in vacuo to provide 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. In a similar manner, other compounds of formula (la) are prepared: 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (N '-methylureido) -amino) methyl) piperazine; NMR (CDC13) 7.2 (m, 4), 7.0 (t, 2), 6.8 (dd, 2), 5.7 (s broad, 1), 5.2 (m, 1), 5.0 (m, 1), 4.8-2.0 (m, 15) ppm; 4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl -2- (N- (ethoxycarbonylmethyl) ureido) methyl) piperazine, NMR (DMSO-dg) 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) -glycinamido) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f-luorobenzyl) piperazine; NMR (CDC13) 9.8 (broad s, 1), 8.3 (s, 1), 7.3 (m, 2), 7.0 (m, 3), 6.8 (d, 1), 6.0 (s broad, 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-fluorobenzyl) piperazine; NMR (DMSO-ds) 9.8 (broad m, 1), 9.4 (s, 1), 8.2 (s, 1), 7.6 (m, 2), 7.3 (m, 2), 7.0 (m, 2), 6.0 (broad m, 2), 5.0 (m, 3), 4.3 (broad m, 3), '4.0 (s.2), 3.7-3.2 (m, 4), 2.8 (s, 3), 1.3 (m, 3), 1.2 (m, 3) ppm, - (trans) -l- ((4-chloro-2 - (N-ethylureido) -f-enoxy) methyl) carbonyl-2, 5-dimethyl-4- (4- f luorobenzyl) piperazine, - NMR (CDCl 3) 8.8 (s, 1), 8.4 (s, 1), 7.3 (m, 2), 7.0 (m, 2), 6.8 (m, 3), 4.7 (m, 2 ), 4.1 (m, 2), 3.6-3.3 (m, 4), 3.0 (broad 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 1 - (2,4-dichlorophenyl) -ureido) phenoxy) methyl) carbonyl -2,5-dimethyl-4 (4-f-luorobenzyl) piperazine; NMR (DMS0-d6) 10.4 (broad 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. O (m, 2), 4.7 (m, 1), 4.3 (m, 3), 3.8 (c, 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-nitrofenyl) -ureido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (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; (trans) -1- ((4-chloro-2- (N '- (4-methylphenyl) -ureido) phenoxy) methyl) carbonyl-2, 5-dimethyl-4 - (4-f-luorobenzyl) piperazine, - NMR (DMSO-dg) 10.5 (broad 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 (m, 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-f luorobenzyl) piperazine, NMR (CDCl 3) 9.0 (s) , 1), 8.4 (s, 1), 7.3 (m, 8), 7.0 (t, 2), 6.8 (c, 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 1 -ethylureido) ethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; ' NMR (CDCl 3) 7.3 (m, 4), 7.0 (t, 2), 6.8 (d, 1), 5.6 (m, 1), 5.4 (broad d, 1) 4.7 (m, 2), 3.5 (c, 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; (trans) -1- ((4-Chloro-2- (oxazol-2-ylaminomethyl) -phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-luobenzyl) piperazine: NMR (CDC13) 7.3 (m, 3), 7.2 (dd, 1), 7.0 (t, 2), 6.8 (d, 1), 4.7 (m, 3), 4.4 (s, 2), 4.3 (t, 2), 3.9 (m, 1 ), 3.8 (t, 2), 3.5 (c, 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-chlorophenyl) -3- (ureido) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) -piperazine; NMR (DMSO-dg) 7.3 (m, 4), 7.2 (m, 2), 7.1 (t, 2), 5.8 (broad s, 1), 5.4 (broad 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-dg) 7.3 (m, 5), 7.1 (t, 2), 6.6 (c, 1), 5.6 (s broad, 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; (t ran s) - 1 - ((4-c l o ro-2 - ((N '- (3-methoxyphenyl) ureido) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-dg) 10.2 (broad s, 1), 9.5 (s, 1), 8.5 (broad s, 1), 8.2 (s, 1), 7.7 (, 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- ((N1 - (trichloromethylcarbonyl) -ureido) f enoxi) methyl) carbonyl-2 , 5-dimethyl-4 - (4-fluorobenzyl) piperazine; NMR (CDC13) 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. 0 (m, 1), 2.7 (dd, 1), 2.2 (d, 1), 1.3 (m, 3), 0.9 (m, 3) ppm. C. In a similar manner, other compounds of formulas (la), (Ib), (le) and (Id) are prepared.

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 anhydrous THF (2 mL) is added 4-fluorobenzyl bromide (0.11). ml, 0.85 mmol), diisopropylethylamine (0.15 ml, 0.85 mmole) and sodium iodide (0.042 g, 0.28 mmole).

The resulting mixture is stirred at room temperature for 2 days. At this time, the mixture is poured into ether and washed with a 5% aqueous solution of NaHCO 3, and then with brine. The organic layer is dried over MgSO4, filtered and concentrated in vacuo to give a yellow oil. Purification by flash column chromatography on silica gel provides 0.17 g of (cis) -1- ((4-chlorophenoxy) methyl) carbonyl-3,5-dimethyl-4- (4-fluorobenzyl) piperazine as a rose oil; which is converted to its hydrochloride salt; NMR (CDC13) 7.6 (m, 2), 7.3 (m, 4), 7.0-6.8 (m, 2), 5.0-2.8 (m, 10), 1.5-1.3 (m, 6) ppm. B. In a similar manner, other compounds of formula (la) are prepared: 1- ((4-chlorophenoxy) methyl) 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), 1.6 (s, 2), 0.8 (m, 1), 0.5 (m, 2), 0.1 (m, 2) ppm, - Hydrochloride salt (3R, 5R) -4- (4-Fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3,5-dimethylpiperazine: NMR (CDC13) 13.3 (m, 1), 7.9 (c, 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, 5S) -4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-3,5-dimethylpiperazine hydrochloride salt; NMR (CDC13) 13.3 (m, 1), 7.9 (c, 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- ((4-chloro-enoxy) methyl) carbonyl-2- ((4-fluorobenzyl) amino) methyl) -4- (4-f luorobenzyl) piperazine; 1 - ((4-chloro-enoxy) methyl) carbonyl-2 - (((methyl) amino) methyl) -4- (4-f luorobenzyl) piperazine: NMR (CDC13) 7.3 (m, 4), 7.0 (t, 2), 6.8 (d, 2). 4.5 (c, 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 1- ((4-chloro-enoxy) methyl) carbonyl-3-trifluoromethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 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. C. In a similar manner, the compounds of formulas (la), (Ib), (ic) and (Id) are prepared.

EXAMPLE 10 Compounds of formula (le) A. To a solution of l- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-4 (benzyl) iperazine (0.15 g, 0.37 mmol) in toluene (10 mL) is added iodomethane (0.15 mL, 2.2 mmoles). The resulting mixture is stirred at room temperature for 4 days. At that time, the solid that precipitates is filtered and washed with ether to provide 0.019 g of 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-4-methyl-4- (benzyl) iperazinium iodide as a white solid; NMR (DMSO-ds) 7.6 (s, 5), 6.3 (s, 2), 4.8 (s, 2), 4.7 (s, 2), 4.2 (d, 1), 4.0 (d, 1), 3.8 ( s, 6), 3.6-3.3 (m, 9), 3.1 (s, 3) ppm. B. In a similar manner, other compounds of formulas (le) are prepared: 1- ((3,4,5-trimethoxyphenoxy) methyl) carbonyl-4-methyl-4- (4-f luorobenzyl) piperazinium iodide; NMR (DMSO-dg) 7.6 (dt, 2), 7.4 (t, 2), 6.3 (s, 2), 4.8 (s, 2), 4.7 (s, 2), 4.2 (d, 1), 4.0 ( d, 1), 3.8 (s, 6), 3.6-3.3 (m, 9), 3.0 (s, 3) ppm; Bromide of 1- ((3,4-, 5-trimethoxyphenoxy) methyl) carbonyl-4- (prop-2-enyl) -4- (4-fluorobenzyl) -piperazinium; NMR (DMSO-dg) 7.6 '(dt, 2). 7.4 (t, 2), 6.2 (m, 3), 5.75 (d, 1), 5.65 (d, 1), 4.8 (s, 2), 4.7 (s, 2), 4.2-3.3 (m, 19) ppm; Bromide of 1- ((3,4-, 5-trimethoxyphenoxy) methyl) carbonyl-4-benzyl-4- (4-fluorobenzyl) piperazinium; NMR (DMSO-dg) 7.7-7.1 (m, 9), 6.2 (s, 2), 4.8 (m, 6), 4.0-3.3 (m, 17) ppm; and 1- (3, 4, 5-trimethoxyphenoxy) methyl) carbonyl-2,4-dimethyl-4- (4-fluorobenzyl) piperazinium iodide; NMR (DMSO-dg) 7.6 (m, 2), 7.2 (m, 4), 7.0 (d, 2), 4.9 (s, 2), 4.6 (s, 2), 3.6-3.3 (m, 7), 3.1 (s, 2), 2.9 (s, 1), 1.2 (m, 3) ppm.

C. In a similar manner, other compounds of formula (le) are prepared.

EXAMPLE 11 Compounds of formula (la) A. To a solution of l- ((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) is added lithium hydroxide monohydrate (0.40 ml, 9.5 mmol). The resulting mixture is stirred at room temperature for 30 min. At that time, the analysis by CLAP shows that complete conversion has occurred. The mixture is poured into ethyl acetate and washed sequentially with a solution of aqueous acetic acid / water (pH < 4), water, and brine. The organic layer is separated, dried over MgSO4, filtered and concentrated in vacuo to provide 0.060 g of 1- (3,4,5-trimethoxyphenoxy) methyl) carbonyl -2- (carboxy) methyl-4- (4 - fluorobenzyl) piperazine as a white solid, - NMR (CDC13) 7.4 (m, 2), 7.1 (m, 2), 6.2 (m, 2), 5.1 (m, 1), 4.7 (m, 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) 476. B. In a similar way , the following compounds of the invention are prepared: 1- ((4-chlorophenoxy) methyl) carbonyl-3- (carboxy) methyl -4- (4-fluorobenzyl) piperazine; NMR (DMSO-dg) 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 (CDC13) 9.4 (broad 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 (m, 2), 3.4 (m, 1), 3.3 (m, 1), 1.4-1.3 (m, 6) ppm. C. In a similar manner, other compounds of formulas (la), (Ib), (le) and (Id) are prepared.

EXAMPLE 12 Compounds of formula (la) A. To a solution of lithium aluminum hydride (0.29 g, 7 mmol) in an anhydrous THF solution (16 mL) is added 1- ((4-chlorophenoxy) methyl) carbonyl-4- (4-fluorobenzyl) - piperazine (0.36 g, 1.0 mmol, in 3 ml of THF). The resulting mixture is stirred at room temperature for 9 hours. At that time, 0.3 ml of water and 0.3 ml of a 15% aqueous solution of NaOH are added and the resulting mixture is stirred at room temperature. After 18 hours, the mixture is filtered through a short column of Celite (THF) and the filtrate is concentrated in vacuo to provide 0.12 g of 1- (2- (4-chlorophenoxy) ethyl) -4- (4- -fluorobenzyl) piperazine as a clear 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. B. In a similar manner, other compounds of formulas (la), (Ib), (le) and (Id) are prepared.

EXAMPLE 13 Compound of formula (Ib) A. To a solution 1- (1- (t-butoxycarbonyl) amino-2- (4-chlorophenyl) ethyl) carbonyl-4 (benzyl) piperazine (0.20 g, 0.44 mmol) in a solution of CH2C12 (3 ml) was add trifluoroacetic acid (3 ml). The resulting mixture is stirred at room temperature. After 18 hours, the mixture is concentrated in vacuo to give a yellow oil. This is dissolved in ethyl acetate and washed with an aqueous solution of NaHCO 3.

The organic layer is separated, dried over MgSO4, filtered and concentrated in vacuo to give 0.17 g of a clear colorless film. This is dissolved in ether and treated with an ethereal HCl solution, which results in the formation of a white precipitate. The concentration affords 0.18 g of 1- (1-amino-2- (4-chlorophenyl) ethyl) carbonyl-4 (benzyl) iperazine as a white solid; NMR (CDC13) 7.4 (m, 7), 7.1 (m, 2), 4.0 (t, 1), 3.7-3.1 (m, 4), 2.8 (m, 2), 2.4-2.2 (m, 5), 1.8 (m, 1) ppm. B. In a similar manner, the following compounds of formula (Ib) are prepared: 1- (3-amino-2- (4-chlorophenyl) rovyl) carbonyl -4- (4-chlorobenzyl) piperazine; NMR (CDC13) 7.2 (m, 8), 3.8 (s, 3), 3.6-3.3 (m, 8), 3. 0 (m, 2), 2.6 (of, 2), 2.4-2.1 (m, 4) ppm, and 1 - "(1-amino-2- (4-chlorophenyl) ethyl) carbonyl-4- (4-chlorobenzyl) ) iperazine; NMR (CDCI3) 7.3 (m, 6), 7.1 (d, 2), 4.0 (t, 1), 3.6- 3.1 (m, 6), 2.8 (of, 2), 2.6 (s broad, 2 ), 2.4 (m, 3), 1.8 (m, 1) ppm C. In a similar manner, the following compounds of formula (la) are prepared: (trans) -1- ((4-chloro-2- ( aminomethyl) -phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) iperazine; NMR (CDCI3) 7.3 (m, 3), 7.2 (dd, 1), 7.0 (t, 2), 6.8 (broad d, 1), 4.7 (m, 2), 3.9 (s, 2), 3.5 (m , 3), 3.0 (broad 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) carbonyl-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 (broad s, 1), 2.7 (dd, 1), 2.2 (d, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; (2R, 5S) -l- ((4-chloro-2- (glycinamide) -phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-dg) 10.0 (s, 1), 8.2 (m 3), 7.6 (s, 1), 7.3 (m, 2), 7.1 (dd, 1), 6.9 (m, 1), 5.2- 4.2 (m, 5), 3.8-2.9 (m, 7), 1.2 (m, 6) ppm; (2R) -l - ((4-chloro-2 - (glycinamide) -phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-dg) 11.4 (broad s, 1), 10.0 (s, 1), 8.3 (broad s, 2), 8.1 (s, 1), 7.8 (m, 2), 7.4 (t, 2). 7.1 (d, 1), 7.0 (d, 1) 5.0 (c, 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- ((N1-methyglycinamido) -phenoxy) methyl) carbonyl -2 5-dimethyl-4- (4-fluorobenzyl) iperazine; NMR (CDCl 3) 9.g (s, 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 (s broad, 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-4- (4-f luorobenzyl) piperazine; NMR (CDC13) 10.2 (s, 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), 3.6-3.2 (m, 5), 3.0 (m, 1), 2.7 (dd, 1 ), 2.2 (d, 1), 1.4 (d, 3), 1.3 (m, 3), 1.0 (broad s, 3) ppm; (trans) -1- ((4-chloro-2 - (1- (methylamino) -ethyl) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) -piperazine; NMR (CDCl 3) 7.3 (m, 3), 7.1 (dd, 1), 7.0 (t, 2), 6.8 (broad d, 1), 4.7 (m, 3), 4.0 (c, 2), 3.6 (c, 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 (d wide, 1), 7.4-7.1 (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), 2.4 (s, 3), 2.2 (m, 1), 1.2 (m, 3), 0.8 (m, 3) ppm; (2R) -1- ((4-chloro-2- ((piperazin-1-yl) methyl) -phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; NMR (DMSO-dg) 9.2 (broad 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; (2R, 2S) -1- ((4-chloro-2- ((piperazin-1-yl) methyl) phenoxy) -methyl) carbonymi-2,5-dimethyl-4- (4-fluorobenzyl) iperazine, NMR ( DMSO-dg) 9.8 (s broad, 1), 9.2 (s broad, 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, 1), 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) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine, - NMR (DMSO -dg) 11.3 (broad 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 (m, 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 (c, 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. ~ D. In a similar manner, other compounds of formulas (la), (Ib), (le) and (Id) are prepared.

EXAMPLE 14 Compounds of formula (la) A. To a solution of (trans) -1- ((4-chloro-2-carboxyphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine (0.217 g, 0.50 mmol) in a solution of tetrahydrofuran (5 ml) at 0 ° C is added isobutyl chloroformate (0.075 g, 0.55 mmole) and N-methylmorpholine (0.0556 g, 0.55 mmole). The resulting mixture is stirred at 0 ° C for 20 min, which results in the formation of a white precipitate. A solution of methylamine in tetrahydrofuran (0.25 ml, 2.0 M, 0.50 mmol) is then added, and the mixture is stirred for an additional 30 min, at which time it is concentrated from the volatile fractions in vacuo. The resulting residue is dissolved in ethyl acetate and washed with water, then with brine, dried over MgSO4, filtered and concentrated to 0.208 g of a foam. This is dissolved in ethyl acetate and treated with an ethereal 1 M HCl solution (excess). The resulting solid is collected by filtration and washed with ethyl acetate. Drying in vacuo gives 0.19 g of (trans) -1- ((4-chloro-2- (methylaminocarbonyl) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine as a white solid; NMR (DMSO-ds) 10.8 (broad d, 1), 9.2 (broad 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 (m, 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) are prepared: (trans) -l - ((4-chloro-2 - ((aminocarbonylmethyl) aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl- 4- (4-fluorobenzyl) piperazine; NMR (DMSO-dg) 9.4 (broad 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 (broad d, 1), 1.2 (broad d, 3), 0.9 (broad d, 3) ppm; (t r a n s) - 1 - ((4-c l or r o - 2 - ((2-aminoethyl) aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDC13) 9.4 (broad 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 (broad d, 1), 2.3 (d, 1), 1.3 (broad d, 3), 1.0 (m, 2) ppm; (trans) -l - ((4-chloro-2 - ((4-aminocarbonylphenyl) aminocarbonyl) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine, - NMR (DMSO-dg ) 11.4 (s, 1), 7.9 (m, 5), 7.7 (d, 1), 7.4 (m, 3), 7.1 (t, 2), 5.4 (d, 1), 5.1 (m, 2), 4.6 (s broad, 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) -1- (2- (4-chlorophenyl) -3- (t-butoxycarbonylamino) propyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; NMR (CDCl 3) 7.3 (m, 4), 7.2 (d, 2), 7.0 (t, 2), 4.8 (s broad, 1), 4.6 (m, 1), 4.0 (ra, 1), 3.4 (m, 6), 3.0 (m, 1), 2.6 (m, 2), 2.1 (m, 1), 1.4 (s, 9), 1.2 (m, 3), 0.9 (m, 3) ppm. C. In a similar manner, other compounds of formulas (la), (Ib), (le) and (Id) are prepared.

EXAMPLE 15 Compound of formula (la) A. To a solution of hydroxylamine hydrochloride (0.17 9, 2.5 mmol) in DMSO (3 mL) is added triethylamine (0.252 g, 2.5 mmol). The mixture is stirred at room temperature for 10 minutes, and then filtered and washed with THF. The filtrate is concentrated in vacuo to remove the THF and 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 is heated at 75 ° C for 20 hours. At this time, the mixture is diluted with water and extracted with ethyl acetate. The organic extract is washed with water, then with brine, and dried over MgSO4, filtered and concentrated in vacuo to provide 0.21 g of an oil. Dissolve 0.030 g of this oil in ethyl acetate and treat with an ethereal solution 1 M HCl (excess). The resulting solid is collected by filtration and washed with ethyl acetate. Drying in vacuo gives 0. 0 2 7 g d e (t ra n s) -l- ((4-c l o r o -2- (hydroxyamidino) f enoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine as a white solid; NMR (CDC13) 7.6 (s, 1), 7.3 (t, 2). 7.2 (dd, 1), 7.0 (t, 2), 6.7 (broad d, 1), 6.1 (s broad, 2), 4.7 (m, 3), 3.7 (broad d, 1), 3.5 (c, 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. B. In a similar manner, other compounds of formulas (la), (Ib), (le) and (Id) are prepared.

EXAMPLE 16 Compounds of formula (la) 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 diethyl azodicarboxylate (0.060 ml) and diphenylphosphoryl azide (0.081 ml) are added. The mixture is stirred at room temperature for 2 days, and then concentrated from the volatile fractions in vacuo. Purification by flash column chromatography on silica gel provides 0.047 g of 1- ((4-chlorophenoxy) methyl) carbonyl-2- (2-azidoethyl) -4- (4-f luorobenzyl) piperazine as a colorless and clear oil , -RMN (CDC13) 7.3 (m, 4), 7.0 (t.2), 6.9 (d, 2), 4.7 (m, 3), 4.4 (broad 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. B "In a similar manner, the compounds of formulas (la), (Ib), (le) and (Id) are prepared.

EXAMPLE 17 Compound of formula (la) A. To a solution of (trans) -1- ((4-chloro-2-aminofenoxi) methyl) carbonyl-2, 5 -dimethyl-4 - (4 -f luorobenzyl) piperazine (0.169 g, 0.416 moles) in 10 ml of methylene chloride, phthalic anhydride (0.074 g, 0.499 mol) and several molecular sieves of 4Á are added. The mixture is stirred at room temperature for 3 hours, and then at 70 ° C for 3 hours. At that time, the mixture is cooled to 0 ° C and treated with oxalyl chloride (0.064 g, 0.499 moles). This is stirred at room temperature for 3 hours and then divided between methylene chloride and water. The organic layer is concentrated to provide an oil. Purification by flash chromatography on silica gel provides 0.058 g of a clear oil. This is dissolved in ethyl acetate and treated with an ethereal solution 1 M HCl (excess). The resulting solid is collected by filtration and washed with ethyl acetate. Drying in vacuo gives 0.045 g of (trans) -1 - ((4-chloro-2- (phthalimido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine as a white solid , - 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 (m, 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) pppm. B. In a similar manner, the following compounds of formula (la) .- (trans) -1- ((4-chloro-2 - (maleimido) -phenoxy) methyl) carbonyl-2, 5-dimethyl-4 are made - (4-fluorobenzyl) piperazine; NMR (CDC13) 7.3 (m, 6), 7.0 (t, 2), 6.8 (s, 1), 4.6 (m, 3), 4.0 (m, 1), 3.5 (c, 2), 3.2 (m, 1), 3.0 (broad s, 1), 2.6 (dd, 1), 2.2 (broad d, 1), 1.2 (m, 3), 0.9 (m, 3) ppm. C. In a similar manner, compounds of formulas (la), (Ib), (le) and (Id) are prepared.

EXAMPLE 18 This example illustrates the preparation of representative pharmaceutical compositions for oral administration containing compound of the invention, or a pharmaceutically acceptable salt thereof, for example, the hydrochloride salt of 1- ((2-methylphenoxy) methyl) carbonyl-4- ( 4-chlorobenzyl) piperazine: TO.

The above ingredients are mixed and supplied in hard shell gelatin capsules containing 100 mg each, one capsule is approximately a total daily dosage.

B.

The above ingredients with the exception of magnesium stearate are combined and granulated using water as the granulating liquid. The formulation is then dried, mixed with the magnesium stearate and tabletted with an appropriate tabletting machine.

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 provide 100 ml of the solution which is filtered and bottled.

The above ingredients are melted, mixed and filled into soft elastic capsules.

AND.

The compound of the invention is dissolved in a cellulose / saline solution, filtered and bottled for use.

EXAMPLE 19 This example illustrates the preparation of a representative pharmaceutical formulation 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: The compound of the invention is dissolved in propylene glycol, polyethylene glycol 400, and polysorbate 80. A sufficient amount of 0.9% saline is then added with stirring to provide 100 ml of I.V. which is filtered through a 0.2 m membrane filter and packed under sterile conditions.

EXAMPLE 20 This example illustrates the preparation of a representative pharmaceutical composition in the form of suppositories containing compound of the invention, or a pharmaceutically acceptable salt thereof, for example 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) -methyl) carbonyl) -2- (2-hydroxyethyl) iperazine: The ingredients are melted together and mixed in a steam bath, and poured into molds containing 2.5 g of total weight.

EXAMPLE 21 This example illustrates the preparation of a representative pharmaceutical formulation for insufflation containing a compound of the invention, or a pharmaceutically acceptable salt thereof, for example (2R, 5R) -4- (4-fluorobenzyl) -1- ((4- chlorophenoxy) methyl) carbonyl) -2,5-dimethylpiperazine: The ingredients are ground, mixed and packed in an insufflator _equipped with a dosing pump.

EXAMPLE 22 This example illustrates the preparation of a representative pharmaceutical formulation in nebulized form containing a compound of the invention, or a pharmaceutically acceptable salt thereof, for example 1- (((4-chlorophenyl) amino) methyl) carbonyl) -4- ( 4-chlorobenzyl) piperazine: The compound of the invention is dissolved in ethanol and combined with water. The formulation is then packed in a nebulizer equipped with a dosing pump.

EXAMPLE 23 This example illustrates the preparation of a representative pharmaceutical formulation in aerosol form containing a compound of the invention, or a pharmaceutically acceptable salt thereof, for example l- ((4-chloro-2- (((ethyl) amino) methyl) phenoxy) methyl) carbonyl) -2,5-dimethyl-4- (4-fluorobenzyl) iperazine: The compound of the invention is supplied in oleic acid and the propellants. The resulting mixture is then poured into an aerosol container to which a metering valve is placed. In the following examples, 293MR cells are used.

These are human embryonic kidney cells (HEK293) which have been stably transfected to express the human CCR1 receptor by the following procedure: HEK293 cells are obtained from American Type Culture Collection (ATCC CRL 1573). CDNA for human CCRl is provided through the collaboration of Dr. Stephen Peiper of the University of Louisville, Kentucky. The CCR1 gene is subcloned using standard techniques (see, eg, Molecular Cloning: A Laboratory Manual, 2nd Edition, Cold Spring Harbor Laboratory Press, 1989) into a standard plasmid containing the SV40 promoter and an extender. The plasmid also contains hygromycin and puromycin resistance genes. Standard transfection protocols with calcium phosphate are used to insert the plasmid into HEK293 cells. The cells are selected for stable expression of CCRl using selection by hygromycin and puromycin. Cells are tested for their ability to bind RANTES or MlP-labeled with 125I with high affinity.

EXAMPLE 24 Essay Trí Vi tro -. Calcium Flow Since the CCR1 receptor, in common with 7 other transmembrane G protein coupled receptors, responds to the binding of its ligand, for example MlP-la and RANTES, by mobilizing free intracellular calcium, one can measure the biological activity by assays of calcium flow using fluorescent dye Fura 2. In the next test, the ability of the compounds of the invention to block their biological response is measured.

Protocol: 1) Two flasks of 293MR cells are detached, washed and resuspended in Hanks Ca2"(50 ml of Hanks, 1M of Hepes 10 ml, 1.6 ml of 500 mM CaCl2, pH 7.4). The cells are washed twice in this medium. 2) The cells are counted, CCR1 = 28 x 10 cells / ml are taken to 2 x 10 6 cells / ml when suspended in 14 ml of Hanks Ca2 +. To 10 ml of these cells (20 x 106) are added 30 ml of medium (containing 50 μg of Fura in 50 μl of DMSO). The final cell concentration is 1.0 x 10e cells / ml. The final concentration of Fura is 1.25 μM. 4) Cells are incubated at 37 ° C for 30 minutes in the presence (or absence) of increasing concentrations of compounds of the invention. The cells are washed as in the above to remove free Fura. The cells are resuspended at 1 x 10 cells / ml. The cells then form aliquots (2.0 ml) in a cuvette and are placed in a spectrofluorimeter. The cells are then stimulated with either MlP-la or RANTES (Peprotech Inc.), and the release of Ca2 + in the spectrofluorimeter is measured.5) The data is corrected for Ca2 + nM released by adding 100 μl of Triton X-100 0.1% (for maximum values) followed by 100 μl of 500 mM EGTA, pH 8.5 (for minimum values).

When tested in this assay, the compounds of the invention demonstrate the ability to inhibit Ca2 + mobilization in response to binding of MlP-la and RANTES to the CCR1 receptor.

EXAMPLE 25 In Vi tro test The tests were performed on a microphysiometer to investigate the functional activity of the antagonist of interest. The microphysiometer determines 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. al., Science (1989), vol 246, pp 243-247). It has been shown that the microphysiometer can be used to measure the 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. Nati Acad. Sci. (1989), vol 87, pp 4007-4011). The following assay demonstrates that activation of CCR1 receptors endogenously expressed in human THP-1 cells with MlP-la and RANTES induces physiological changes that result in an increase in metabolic rates and further that the compounds of the invention inhibit this effect from a way dependent on the dose.

Materials : Cytosensor capsule equipment (Molecular Devices Cat # R8013). 2 Agarose entrapment medium (Molecular Devices Cat # R8023). Medium modified PRMI 1640 for cytosensor, low buffered (Molecular Devices Cat # R8023). 4 Cytosensing sterilizing equipment (Molecular Devices Cat # R8017). 5. Reference Electrode Maintenance Equipment (Molecular Devices Cat # 0310-2805). 6. Working solution for MlP-la or RANTES (Peprotech Inc.): 10 μM in modified RPMI 1640 medium (Molecular Devices Cat # R8016) supplemented with BSA 1 mg / ml (bovine serum albumin), 100 units / ml penicillin and 100 μg / ml streptomycin). This working solution is referred to below as a "modified culture medium". 7 Working solution MCP-1: 10 μM in modified culture medium. The compounds in the concentrated solution of the invention: 1 mM in DMSO (stored at room temperature). 9 Cell culture: a. THP-1 (ATCC Cat # TIB202). b. Tissue culture medium: RPMI 1640 supplemented with 10% FBS (fetal bovine serum). This medium is referred to below as "growth medium".

Procedure test: THP-1 cells are grown in T-25 cm 2 flasks in growth medium at 37 ° C, 5.0% C02, 95% air to a cell density of 1 x 10 cells / ml. The cells are harvested by centrifugation (5 minutes at 20 G) and resuspended in modified growth medium. The cell count is performed by exclusion of Trypan blue dye and the cells are _ > 90% viable. The cells are again centrifuged, removed on a swirling surface and the resulting pellet is resuspended to a final cell concentration of 1 x 10s / 0.1 ml. The entrapment reagent in agarose cells is melted and placed in a 37 ° C water bath. A cell suspension is prepared: 0.15 ml of THP-l cells are added to a 1.5 ml centrifuge tube with 50 μl of the molten agarose solution. In addition to the capsule containers: the capsule containers are placed in a 12-well microtiter plate, a separator is added to the capsule container, and 7 μl of cell / agarose suspension is pipetted onto the container center. After 3 minutes, 1 ml of modified growth medium is pipetted out of the capsule container, and 200 μl of the modified growth medium is pipetted into the interior. The capsule insert is then placed in the container with a sterile forcep and 500 μl of modified culture medium is pipetted into the insert. The completed capsule is loaded in cameras of the microphysiometer. The chambers are perfused at a rate of 100 μl / minute with modified culture medium. The pumping cycle is 50 seconds on and 40 seconds off. The multiple data points that represent the metabolic rate are taken and used as a baseline. The cells are exposed to the compounds of the invention for 30 minutes before the addition of the chemokine agonists to a final concentration of 10 nM. The treated and untreated cells were exposed with agonists for 100 seconds and the data was collected. When tested in this assay, the compounds of the invention demonstrated the ability to inhibit the activity of the CCR1 receptor by MlP-la or RANTES.

EXAMPLE 26 In Vitro Assay In Vitro Assay for CCRl 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 for the CCR1 receptor are determined by their ability to compete with 15I-MIP-la or 1 5I-RANTES for binding to the CCR1 receptor.

Reagents and Solutions: MlP-la and RANTES (Peprotech Inc.) Cells: 293MR cells (KD = 1-3 nM and Bmax = 2-3 x 10s sites / cell) are shed by trypsinization and plated in flasks at least 48 hours before of the experiment. Ligand: 125 I-MIP-I and 12 I-RANTES from New England Nuclear (the specific activity is 2200 Ci / mmol, 25 μCi / vial) is reconstituted in 1 ml of H20. Assay buffer: 130 mM NaCl, 5 mM KCl, 1 mM MnCl 2, 50 mM Tris, 30 μg / ml bacitracin, 0.1% BSA, pH 7.4. Shock absorber: Phosphate buffer solution (PBS). Compounds of the invention: The concentrated solution of the compounds is 1 mM in 100% DMSO. The highest concentration in the assay is 10 μM and can vary based on the potency of the compounds. A 1: 3 serial dilution is made from the highest concentration with the assay buffer. Usually, 6 concentrations of each compound are analyzed to generate a dose curve from which the Kx value is determined.

Test Procedure: The assays are performed in 96-well v-shaped microtiter plates in a total volume of 100 μl. 293MR cells are separated from the 225 cm2 T flask in PBS by shaking. The cells are washed once in PBS and resuspended in the assay buffer to approximately 1.1 x 10? cells / ml. The cells are incubated (approximately 8000 cells / assay) with either • I-MIP-the 'I-RANTES (approximately 15,000-20,000 cpm / test) in the presence and absence of different concentrations of compounds at room temperature for 30-40 minutes. The reactions end when collecting through a GF / B filter plate pre-wetted with PEI 0.3% (Sigma # P-3143) plus 0.5% BSA and washing five times with cold PBS. The radioactivity in each well is determined by scintillation counting followed by the addition of 50 μl of scintillation fluid.

Non-specific binding is defined as binding in the presence of 100 nM of unlabeled MlP-la or RANTES. The concentration of the CCR1 receptor used in the assay is 0.4 nM and 125 I-MIP-la or 125 I-RANTES is 0.06 nM. The concentrations of the compounds in the assay are typically 10 μM to 30 nM in 1: 3 dilutions, and the concentrations for more potent compounds are lower, depending on the potency.

Calculations: The dose curves of each compound are generated with 6 concentration points and the CIS0 values are determined by fitting the data to the log-logit (linear) equation with an EXCEL analysis sheet. The K ± values are then calculated by dividing the IC50 by 1.025 to correct the concentration of the tagged ligand. When tested in this assay, the compounds of the invention demonstrate their affinity for binding to the CCR1 receptor.

Claims

not. CLAIMS: A compound of the following formula (la) wherein: Rla is one or more substituents independently selected from the group consisting of oxo, halo, (C 1 -C 8) alkyl, (C 3 -C 10) cycloalkyl, (C 3 -C 10) cycloalkyl (C 1 -C 8) alkyl, (C 3) cycloalkyl -C10) amino (C 1 -C 8) alkyl, (C 3 -C 10 cycloalkyl) alkyl (C 1 -C 8) alkylamino (C 1 -C 8) alkyl, haloalkyl (C 1 -C 8), alkenyl (C 2 -C 8), alkynyl (C 2 -C 8) ), phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, (phenyl or naphthyl) alkenyl (C2-C8), formyl, formylalkyl (C1-C8), hydroxyalkyl (C1-C8), hydroxyalkenyl (C2- C8), hydroxyalkynyl (C2-C8), (hydroxy) (phenyl or naphthyl) alkyl (C1-C8), (hydroxy) (C3-C10) cycloalkyl (C1-C8) alkyl, (C1-C8) mercaptoalkyl, cyanoalkyl ( C1-C8), (C1-C8) haloalkyl carbonylamino (C1-C8) alkyl, (C1-C8) alkoxy (phenyl or naphthyl) (C1-C8) alkyl, (C1-C8) alkoxy (C1-C8) alkyl , (phenyl or naphthyl) oxyalkyl (C1-C8), (phenyl or naphthyl) alkoxy (C1-C8) alkyl (C1-C8), alkyl (C1-C8) thioalkyl (C1-C8), alkyl (Cl-C8) sui f inilalqu ilo (C1-C8), alkyl (C1-C8) sulfonylalkyl (C1-C8), hydroxyalkyl (C1-C8) thioalkyl (C1-C8), aminoalkyl (C1-C8), monoalkyl (C1-C8) aminoalkyl (C1- C8), dialkyl (C1-C8) aminoalkyl (C1-C8), mono (phenyl or naphthyl) aminoalkyl (C1-C8), mono (phenyl or naphthyl) alkyl (C1-C8) aminoalkyl (C1-C8), alkyl ( C1-C8) carbonylamino (C1-C8) alkyl, (C1-C8 alkyl) carbonyl) (C1-C8 alkyl) amino (C1-C8) alkyl, (C1-C8) azidoalkyl, (C1-C8) ureidoalkyl, monoalkyl (C1-C8) ureidoalkyl (C1-C8), dialkyl (C1-C8) ureidoalkyl (C1-C8), (C1-C8 alkoxy) carbonylalkyl (C1-C8)) ureidoalkyl (C1-C8), alkoxy (C1- C8) carbonylaminoalkyl (C1-C8), hydroxyalkyl (C1-C8) aminoalkyl (C1-C8), (phenyl or naphthyl) oxyalkyl (C1-C8) carbonyloxyalkyl (C1-C8), alkoxy (C1-C8) alkyl (C1- C8) carbonyloxyalkyl (C1-C8), (phenyl or naphthyl) alkoxy (C1-C8) alkyl (C1-C8) carbonyloxyalkyl (C1-C8), alkyl (C1-C8) carbonyl, alkyl (C1-C8) carbonylalkyl (C1 -C8), carboxy, (C1-C8) alkoxycarbonate an onyl, (phenyl or naphthyl) (C1-C8) alkoxycarbonyl, (phenyl or naphthyl) alkyl (C1-C8) carbonyl, aminocarbonyl, (C1-C8) monoalkylaminocarbonyl, dialkyl (C1-C8) aminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, mono (phenyl or naphthyl) aminocarbonylalkyl (C 1 -C 8), carboxyalkyl (C 1 -C 8), alkoxy (C 1 -C 8) carbonylalkyl (C 1 -C 8), (phenyl or naphthyl) alkoxy (C 1 -C 8) carbonylalkyl ( C1-C8), aminocarbonylalkyl (C1-C8), monoalkyl (C1-C8) aminocarbonylalkyl (C1-C8), dialkyl (C1-C8) aminocarbonylalkyl (C1-C8), mono (phenyl or naphthyl) aminocarbonylalkyl (C1-C8) , mono (phenyl or naphthyl) alkyl (C1-C8) aminocarbonylalkyl (C1-C8), (phenyl or naphthyl) sulfonyl, heterocyclyl of 3-15 members consisting of carbon atoms and one to five heteroatoms selected from the group consisting of of nitrogen, oxygen and sulfur and (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and ufre) (C 1 -C 8) alkyl, - R 2 is one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, (C 1 -C 8) alkyl, mercapto, mercapto (C 1 -C 8) alkyl, alkylthio (C 1) -C8), rent (C1-C8) sulfonyl, alkyl (C1-C8) sufonyl, alkyl (C1-C8) thioalkyl (C1-C8), alkyl (C1-C8) sulfinylalkyl (C1-C8), alkyl (C1-C8) sulfonylalkyl (C1-C8), alkoxy (C1-C8), (phenyl or naphthyl) oxy, haloalkyl (C1-C8), formyl, formylalkyl (C1-C8), nitro, nitroso, cyano, (phenyl or naphthyl) alkoxy (C1-C8), haloalkoxy (C1-C8), cycloalkyl (C3-C10), (C3-C10) cycloalkyl (C1-C8) alkyl, (hydroxy) (C3-C10) cycloalkyl (C1-C8) alkyl, (C3-C10) cycloalkyl amino, (C3-C10) cycloalkyl (C1-C8) aminoalkyl, (C3-C10) cycloalkyl (C1-C8) alkyl) amino, (C3-C10) alkyl (C1-C8) alkyl) amino (C1-C8) alkyl, cyano (C1-C8) alkyl, (C2-C8) alkenyl , (C2-C8) alkynyl, phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, (phenyl or naphthyl) alkenyl (C2-C8), hydroxyalkyl (C1-C8), (hydroxy) (phenyl or naphthyl) alkyl (C1-C8), hydroxyalkyl (C 1 -C 8) thio (C 1 -C 8) alkyl, (C 2 -C 8) hydroxyalkenyl, (C 2 -C 8) hydroxyalkynyl, (C 1 -C 8) alkoxy (C 1 -C 8) alkyl, (C 1 -C 8) alkoxy) phenyl or naphthyl) (C 1 -C 8) alkyl, (phenyl or naphthyl) oxyalkyl (C 1 -C 8), (phenyl or naphthyl) (C 1 -C 8) alkoxy (C 1 -C 8) alkyl, amino, (C 1 -C 8) aminoalkyl) amino , dialkyl (C1-C8) amino, mono (phenyl or naphthyl) amino, mono (phenyl or naphthyl) (C1-C8) alkyl amino, (C1-C8) aminoalkyl, (C1-C8) monoalkyl amino (C1-C8) alkyl, (C1-C8) dialkylamino (C1-C8) alkyl, hydroxyalkyl (C1- C8) (C1-C8) aminoalkyl, mono (phenyl or naphthyl) aminoalkyl (C1-C8), mono (phenyl or naphthyl) alkyl (C1-C8) aminoalkyl (C1-C8), alkyl (C1-C8) carbonylamino, ( (C 1 -C 8) alkylcarbonyl) (C 1 -C 8 alkyl) amino, (C 1 -C 8) alkylcarbonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkylcarbonyl) (C 1 -C 8 alkyl) aminoalkyl ( C1-C8), (C1-C8) alkoxycarbonylamino, (C1-C8alkoxy) carbonyl) (C1-C8alkyl) amino, (C1-C8) alkoxycarbonylaminoalkyl (C1-C8), (C1-6alkoxy) C8) carbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, carboxy, (C 1 -C 8) alkoxycarbonyl, (phenyl or naphthyl) (C 1 -C 8) alkoxycarbonyl, (C 1 -C 8) alkylcarbonyl, (C 1 -C 8) alkylcarbonylalkyl (C 1 -C 8) alkyl, (phenyl or naphthyl) carbonyl, (phenyl or naphthyl) carbonylalkyl (C 1 -C 8), (phenyl or naphthyl) alkyl (C 1 -C 8) carbonyl, (phenyl or naphthyl) (C 1 -C 8) alkylcarbonylalkyl (C1-C8), carboxyalkyl (C1-C8), alkoxy (C1-C8) carbonylalkyl (C1-C8), (phenyl or naphthyl) (C1-C8) alkoxycarbonylalkyl (C1-C8), alkoxy (C1-C8) alkyl (C1-C8) carbonyloxyalkyl (C1-C8), aminocarbonyl, monoalkyl (C1-C8) aminocarbonyl, dialkyl (C 1 -C 8) aminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonyl, aminocarbonylalkyl (C 1 -C 8), mono (C 1 -C 8) alkyl aminocarbonylalkyl (C 1 -C 8), dialkyl (C 1 -C 8) aminocarbonylalkyl (C 1 -C 8), mono (phenyl or naphthyl) aminocarbonylalkyl (C 1 -C 8), mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonylalkyl (C 1 -C 8), amidino, guanidino, ureido, mono (C1-C8) ureido, dialkyl (C1-C8) ureido, ureidoalkyl (C1-C8), (C1-C8) monoalkyl ureido (C1-C8) alkyl, (C1-C8) dialkyldido (C1-C8) alkyl, 3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, and (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) alkoyl (C1-C8) , - R3 is a carbocyclic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, (C1-C8) alkoxy, mercapto, (C1-C8) mercaptoalkyl, alkylthio (C1- C8), (C 1 -C 8) alkyl sulfinyl, (C 1 -C 8) alkyl, suphonyl, (phenyl or naphthyl) sulfonyl, alkyl (C 1 -C 8) thioalkyl (C 1 -C 8), alkyl (C1-C8) sulfinylalkyl (C1-C8), alkyl (C1-C8) sulfonylalkyl (C1-C8), (C1-C8) alkoxy, (C1-C8) hydroxyalkoxy, (phenyl or naphthyl) oxy, (C1-C8) haloalkyl, formyl, formylalkyl (C1-C8), nitro, nitroso, cyano, ( phenyl or naphthyl) (C1-C8) alkoxy, (C1-C8) haloalkoxy, (C1-C8) aminoalkoxy, (C3-C10) cycloalkyl, (C3-C10) cycloalkyl (C1-C8) alkyl, (hydroxy) cycloalkyl (C3-C10) (C1-C8) alkyl, (C3-C10) cycloalkyl amino, (C3-C10) cycloalkyl (C1-C8) amino, (C1-C8) cyano (C1-C8) alkyl, (C2-C8) alkenyl, (C2) alkynyl -C8), phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, (phenyl or naphthyl) alkenyl (C2-C8), hydroxyalkyl JC1-C8), (hydroxy) (phenyl or naphthyl) alkyl (C1-C8), ((C1-C8) monoalkyl) amino (phenyl or naphthyl) alkyl (C 1 -C 8), (C 1 -C 8 hydroxyalkyl) thio (C 1 -C 8) alkyl, (C 2 -C 8) hydroxyalkenyl, (C 2 -C 8) hydroxyalkynyl, (C 1 -C 8) alkoxy (C 1 -C 8) alkyl, (alkoxy) (C1-C8)) (phenyl or naphthyl) alkyl (C1-C8), (phenyl or naphthyl) oxyalkyl (C1-C8), (phenyl or naphthyl) (C1-C8) alkoxy (C1-C8) alkyl, amino, (C1-C8) aminoalkyl, dialkyl (C1- C8) amino, mono (phenyl or naphthyl) amino, mono (phenyl or naphthyl) alkyl (C 1 -C 8) amino, amino (C 1 -C 8) aminoalkyl) amino, (3-15 membered heterocyclyl consisting of carbon atoms and from one to five hydrocarbons selected from the group consisting of nitrogen, oxygen and sulfur) amino (C3-C10) cycloalkyl (C1-C8) alkyl) amino, alkylcarbonylamino , (C1-C8) alkoxycarbonylamino, (C2-C8) alkenylcarbonylamino, (C3-CIO) cycloalkylcarbonylamino, (phenyl or naphthyl) carbonylamino, (3-15 membered heterocyclyl consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylamino, (C1-C8) haloalkyl carbonylamino, (C1-C8) alkoxy alkyl (C1 -C8) carbonylamino, (C 1 -C 8) alkoxycarbonylalkyl (C 1 -C 8) carbonylamino, (C 1 -C 8 alkylcarbonyl) (C 1 -C 8 alkyl) amino, (C 1 -C 8 alkoxycarbonyl) (C 1 -C 8 alkyl) amino, alkyl (C1-C8) sulfonylamino, (C1-C8) aminoalkyl, (C1-C8) monoalkylamino (C1-C8) alkyl, (C1-C8) dialkylamino (C1-C8) alkyl, hydroxy (C1-C8) alkylaminoalkyl (C1- C8), mono (phenyl or naphthyl) aminoalkyl (C1-C8), mono (phenyl or naphthyl) alkyl (C1-C8) aminoalkyl (C1-C8), alkyl (C1-C8) carbonylaminoalkyl (C 1 -C 8), (phenyl or naphthyl) carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) carbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (C3-C10) cycloalkyl (C1-C8) alkyl) amino (C1-C8) alkyl, (C1-C8) alkoxycarbonylamino (C1-C8) alkyl, (C1-C8) alkoxy (C1-C8) carbonylalkyl-carbonylaminoalkyl (C1- C8), (C 1 -C 8 alkoxycarbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (C 1 -C 8) alkyl sulfonylamino (C 1 -C 8) alkyl, (alkyl) (C 1 -C 8) sulfonyl) (C 1 -C 8 alkyl) • amino (C 1 -C 8) alkyl, (phenyl or naphthyl) sulfonylamino (C 1 -C 8) alkyl, ((phenyl or naphthyl) sulfonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) aminoalkyl (C 1 -) C8), carboxy, (C1-C8) alkoxycarbonyl, (phenyl or naphthyl) (C1-C8) alkoxycarbonyl, alkyl (C1-C8) carbonyl, (phenyl or naphthyl) carbonyl, (phenyl or naphthyl) alkyl (C1-C8) carbonyl, (hydroxy (C1-C8) alkoxy) carbonyl, carboxyalkyl (C1-C8), alkoxy (C1-C8) carbonylalkyl (C1-C8), (phenyl or naphthyl) (C1-C8) alkoxycarbonylalkyl (C1-C8), alkoxy (C1-C8) alkyl (C1-C8) carbonyloxyalkyl (C1-C8), dialkyl (C1-C8) aminocarbonyloxyalkyl (C1-C8) alkyl (C1-C8) carbonylalkyl (C1-C8), (phenyl or naphthyl) 'carbonylalkyl (C1-C8), (phenyl or naphthyl) alkyl (C1-C8) carbonylalkyl (C1-C8), aminocarbonyl, (C1-C8) monoalkyl aminocarbonyl, dialkyl (C1-C8) aminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, mono (phenyl or naphthyl) aminocarbonylalkyl (C1-C8), (aminocarbonylalkyl (C 1 -C 8)) aminocarbonyl, (C 1 -C 8) monoalkyl aminocarbonylalkyl (C 1 -C 8) alkyl aminocarbonyl, (carboxyalkyl) (C 1 -C 8)) aminocarbonyl, (C 1 -C 8 alkoxy) carbonylalkyl (C 1 -C 8) aminocarbonyl, (C 1 -C 8) aminocarbonyl aminocarbonyl, (hydroxy (C1-C8) alkyl) aminocarbonyl, aminocarbonylalkyl (C1-C8), (C1-C8) monoalkylaminocarbonylalkyl (C1-C8), dialkyl (C1-C8) aminocarbonylalkyl (C1-C8), mono (phenyl or naphthyl) aminocarbonylalkyl (C1-C8), mono (phenyl or naphthyl) ) rent (C 1 -C 8) aminocarbonylalkyl (C 1 -C 8), amidino, hydroxyamidino, guanidino, ureido, mono (C 1 -C 8) alkyl ureido, mono (phenyl or naphthyl) ureido, mono (phenyl or naphthyl) alkyl (C 1 -C 8) ureido, monohaloalkyl (C1-C8) ureido, ((C1-C8) monoalkyl) (mono (phenyl or naphthyl)) ureido, dialkyl (Cl-C8) ureido, di (phenyl or naphthyl) ureido, (haloalkyl (C1-C8) carbonyl) ureido, ureidoalkyl (C1-C8), (C1-C8) monoalkyl ureidoalkyl (C1-C8), dialkyl (C1-C8) ureidoalkyl (C1-C8), mono (phenyl or naphthyl) ureidoalkyl (C1-C8), mono (phenyl or naphthyl) alkyl (C1-C8) ureidoalkyl (C1-C8), monohaloalkyl (C1-C8) ureidoalkyl (C1-C8), (haloalkyl) (C 1 -C 8)) (C 1 -C 8 alkyl) ureido (C 1 -C 8) alkyl, (C 1 -C 8 alkoxy) carbonylalkyl (C 1 -C 8)) ureido (C 1 -C 8) alkyl, glycinamide, (C 1 -C 8) monoalkyl glycinamide, aminocarbonylglycinamide, (C 1 -C 8 alkoxy) C 1 -C 8 alkylcarbonyl) glycinamide, (aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, (C 1 -C 8 alkoxycarbonyl) C 1 -C 8 alkylcarbonyl (C 1 -C 8 alkyl) glycinamide, (C 1 -C 8 alkoxy carbonylamino) (C 1 -C 8) alkylcarbonyl) glycinamide, (phenyl or naphthyl) carbonylglycinamide, ((phenyl or naphthyl) carbonyl) (C 1 -C 8 alkyl) C8)) glycinamide, (mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonyl) glycinamide, (mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, (mono ( phenyl or naphthyl) aminocarbonyl) glycinamide, (mono (phenyl or naphthyl) aminocarbonyl) (C1-C8 alkyl) glycinamide, glycinamide (C1-C8), alaninamide, monoalkyl (C1-C8) alaninamido, alaninamidoalkyl (C1-C8), heterocyclyl 3-15 members consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group which consists of nitrogen, oxygen and sulfur) (C1-C8) alkyl, - or R3 is a 3-15 membered heterocyclic ring system consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, Oxygen and sulfur, substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, (C 1 -C 8) alkyl, (C 1 -C 8) alkyl, suphonyl, (phenyl or naphthyl) sulfonyl, (C 1 -C 8) alkoxy ), hydroxyalkoxy (C1-C8), haloalkyl (C1-C8), formyl, nitro, cyano, haloalkoxy (C1-C8), alkenyl (C2-C8), alkynyl (C2-C8), phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, amino, (C1-C8) monoalkyl amino, dialkyl (C1-C8) amino, mono (fe nyl or naphthyl) amino, mono (phenyl or naphthyl) alkyl (C 1 -C 8) amino, (C 1 -C 8) alkyl carbonylamino, (C 1 -C 8) alkoxy carbonylamino, (C 2 -C 8) alkenyl carbonylamino, (C 3 -C 10) cycloalkyl) carbonylamino, (phenyl or naphthyl) carbonylamino, haloalkyl (C 1 -C 8) carbonylamino, alkoxy (C 1 -C 8) alkyl (C 1 -C 8) carbonylamino, alkoxy (C 1 -C 8) carbonylalkyl (C 1 -C 8) _ carbonylamino, (alkyl ( C1-C8) carbonylalkyl (C1-C8) amino), (C1-C8 alkoxy) carbonyl) (C1-C8 alkyl) amino, (C1-C8) alkyl sulfonylamino, (C1-C8) aminoalkyl, monoalkylaminoalkyl (C1 -C8), dialkyl (C1-C8) aminoalkyl (C1-C8), alkyl (C1-C8) carbonylaminoalkyl (C1-C8), (phenyl or naphthyl) carbonylaminoalkyl (C1-C8), (C1-C8alkyl) carbonyl ) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (C 1 -C 8) alkoxy carbonylamino (C 1 -C 8) alkyl, carboxy, (C 1 -C 8) alkoxycarbonyl, (phenyl or naphthyl) (C 1 -C 8) alkoxy carbonyl, (C 1 -C 8) alkylcarbonyl, (phenyl or naphthyl) carbonyl, (phenyl or naphthyl) (C1-C8) alkylcarbonyl, aminocarbonyl, (C1-C8) monoalkylaminocarbonyl, dialkyl (C1-C8) aminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, aminocarbonylalkyl (C1-C8), monoalkyl (C1- C8) aminocarbonylalkyl (C1-C8), dialkyl (C1-C8) aminocarbonylalkyl (C1-C8), mono (phenyl or naphthyl) aminocarbonylalkyl (C1-C8), guanidino, ureido, monoalkyl (Cl -C8) ureido, ureidoalkyl (C1-C8), monoalkyl (C1-C8) ureidoalkyl (C1-C8), and glycinamide; R4 is -0-, -N (R7) -, -C (R8) 2- or a bond; R5 is an alkylene chain or a C1-C8 alkylidene chain, or, if R4 is a bond, R5 is a C1-C8 alkylidene chain optionally substituted by (phenyl or naphthyl) or -N (R7) 2; R5 is -C (O) -, -C (S) -, -CH2- or a bond, - each R7 is independently selected from the group consisting of hydrogen, (C1-C8) alkenyl, phenyl or naphthyl, (phenyl or naphthyl) (C 1 -C 8) alkyl, (C 1 -C 8) alkylcarbonyl, (C 1 -C 8) alkylcarbonylalkyl (C 1 -C 8), (phenyl or naphthyl) alkyl (C 1 -C 8) carbonyl, (phenyl or naphthyl) alkyl (C 1 -C 8) carbonylalkyl (C 1 -C 8), aminocarbonyl, mono (C 1 -C 8) alkyl aminocarbonyl, dialkyl (C 1 -C 8) aminocarbonyl, and (C 1 -C 8) alkoxy carbonyl; and each R8 is independently selected from the group consisting of hydrogen, (C1-C8) alkyl, phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, hydroxy, (C1-C8) alkoxy, hydroxyalkyl (C1-C8) ), (C 1 -C 8) alkoxy (C 1 -C 8) alkyl, amino, (C 1 -C 8) aminoalkyl, dialkyl (C 1 -C 8) amino, alkyl (C 1 -C 8) carbonylamino, cycloalkyl (C 3 -C 10) carbonylamino, cycloalkyl (C3-C10) (C1-C8) alkylcarbonylamino, (C1-C8) alkoxycarbonylamino, (C1-C8) alkyl sulfonylamino, (phenyl or naphthyl) carbonylamino, (C1-C8) alkoxycarbonylalkyl (C1-C8) carbonylamino, (C 1 -C 8 alkylcarbonyl) (C 1 -C 8 alkyl) amino, (phenyl or naphthyl) alkyl (C 1 -C 8) carbonylamino, ((phenyl or naphthyl) alkyl (C 1 -C 8) carbonyl) (alkyl (C1) Amino) -C8), (C 1 -C 8) alkylcarbonylamino (C 1 -C 8) alkyl, cycloalkylcarbonylamino (C 1 -C 8) alkyl, (C 1 -C 8) alkoxy carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) carbonyl) (C 1 -C 8 alkyl) ) aminoalkyl, (phenyl or naphthyl) alkyl (C 1 -C 8) carbonylamino (C 1 -C 8) alkyl, (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylaminoalkyl (C 1 -C 8), ((phenyl or naphthyl) alkyl (C 1 -C 8) carbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (phenyl or naphthyl) sulfonylamino, alkyl (C 1 -C 8) C8) sulfonylamino (C1-C8) alkyl, ureido, (C1-C8) ureido monoalkyl, (C1-C8) monohaloalkyl ureido, dialkyl (C1-C8) ureido, ureido (C1-C8) alkyl, (C1-C8) monoalkyl ureidoalkyl ( C1-C8), dialkyl (C1-C8) ureidoalkyl (C1-C8), monohaloalkyl (C1-C8) ureidoalkyl (C1-C8), aminoalkyl (C1-C8), monoalkyl (C1-C8) aminoalkyl (C1-C8) , (C1-C8) dialkylamino (C1-C8) alkyl, carboxyalkyl (C1-C8), alkyl oxy (C1-C8) carbonylalkyl (C1-C8), aminocarbonylalkyl (C1-C8), monoalkyl (C1-C8) aminocarbonylalkyl (C1-C8), and dialkyl (C1-C8) aminocarbonylalkyl ((C1-C8)); with the proviso that when R4 is -N (R7) -, Rs is an alkylene chain and Rs is -C (0) -, -C (S) - or CH2-, R3 can not be a saturated heterocyclic ring system from bridge to monocyclic containing 4-8 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 heterocyclic ring system containing 4-6 members consisting of carbon atoms and two nitrogen atoms, and a single stereoisomer or a mixture thereof; or a pharmaceutically acceptable salt thereof. 2. The compound as described in claim 1, wherein: R3 is a carbocyclic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, (C1-C8) alkyl, mercapto , mercaptoalkyl (C1-C8), alkylthio (C1-C8), (C1-C8) alkyl sulfinyl, (C1-C8) alkylsulfonyl, (phenyl or naphthyl) sulfonyl, (C1-C8) alkylthio (C1-C8) alkyl, (C1-C8) alkylsulfinylalkyl ( C1-C8), (C1-C8) alkyl sulfonylalkyl (C1-C8), alkoxy (C1-C8), hydroxyalkoxy (C1-C8), (phenyl or naphthyl) oxy, haloalkyl (C1-C8), formyl, formylalkyl ( C1-C8), nitro, nitroso, cyano, (phenyl or naphthyl) alkoxy (C1-C8), haloalkoxy (C1-C8), aminoalkoxy (C1-C8), cycloalkyl (C3-C10), cycloalkyl (C3-C10) (C 1 -C 8) alkyl, (hydroxy) (C 3 -C 10) cycloalkyl (C 1 -C 8) alkyl, (C 3 -C 10) cycloalkyl amino, (C 3 -C 10) cycloalkyl (C 1 -C 8) alkyl, (C 1 -C 8) cyano (C 1 -C 8) alkyl , (C2-C8) alkenyl, (C2-C8) alkynyl, phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, (phenyl or naphthyl) alkenyl (C2-C8), hydroxyalkyl (C1-C8), (hydroxy) (phenyl or naphthyl) (C1-C8) alkyl, ((C1-C8) amino) (phenyl or naphthyl) alkyl (C1-C8), (hydroxy (C1-C8) alkyl) thio (C1-C8) alkyl , hydroxyalkenyl (C2-C8), hydroxyalkynyl (C2-C8), alkoxy (C1-C8) (C1-C8) alkyl, (C1-C8) alkoxy (phenyl or naphthyl) (C1-C8) alkyl, (phenyl or naphthyl) oxyalkyl (C1-C8), (phenyl or naphthyl) alkoxy (C1-C8) (C1-C8) alkyl, amino, (C1-C8) aminoalkyl, (C1-C8) dialkylamino, mono (phenyl or naphthyl) amino, mono (phenyl or naphthyl) alkyl (C1-C8) amino, amino (C1-C8) aminoalkyl, 3-15 membered heterocyclyl consisting of carbon atoms and one to hetero hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, amino, (C3-C10 cycloalkyl) (C 1 -C 8) alkylamino, (C 1 -C 8) alkylcarbonylamino, (C 1 -C 8) alkoxycarbonylamino, (C 2 -C 8) alkenylcarbonylamino, (C 3 -C 10) cycloalkylcarbonylamino, (phenyl or naphthyl) carbonylamino, (heterocyclyl) 3-15 membered consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylamino, (C1-C8) haloalkyl carbonylamino, (C1-C8) alkoxy (C1-C8) alkyl ) carbonylamino, (C 1 -C 8) alkoxycarbonylalkyl (C 1 -C 8) carbonylamino, (C 1 -C 8 alkyl) carbonyl) (C 1 -C 8 alkyl) amino, (C 1 -C 8 alkoxycarbonyl) (C 1 -C 8 alkyl) amino, alkyl (C1-C8) sulfonylamino, (C1-C8) aminoalkyl, (C1-C8) monoalkylamino (C1-C8) alkyl, (C1-C8) dialkylamino (C1-C8) alkyl, hydroxy (C1-C8) alkylaminoalkyl (C1- C8), mono (phenyl or naphthyl) aminoalkyl (C1-C8), mono (phenyl or naphthyl) alkyl (C1-C8) aminoalkyl (C1-C8), alkyl (C1-C8) carbonylaminoalkyl (C1-C8), (phenyl or naphthyl) carbonylaminoalkyl (C1-C8), (alkyl) (C 1 -C 8) carbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (C 1 -C 8) cycloalkylamino (C 1 -C 8) alkyl, (C 1 -C 8) alkoxy carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8) alkoxycarbonylalkyl (C1-C8) carbonylaminoalkyl (C1-C8), (C1-C8alkoxy) carbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, alkyl (C 1 -C 8) sulfonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) sulfonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (phenyl or naphthyl) sulfonylamino (C 1 -C 8) alkyl, (( phenyl or naphthyl) sulfonyl) (alkyl (C1-C8)) (C1-C8) aminoalkyl, (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) aminoalkyl (C1-C8) , carboxy, (C1-C8) alkoxycarbonyl, (phenyl or naphthyl) (C1-C8) alkoxycarbonyl, (C1-C8) alkylcarbonyl, (phenyl or naphthyl) carbonyl, (phenyl or naphthyl) alkyl (C1-C8) carbonyl, (hydroxy (C1-C8) alkoxy) carbonyl, carboxyalkyl (C1-C8), alkoxy (C1-C8) carbonylalkyl (C1-C8), (phenyl or naphthyl) alkoxy (C1-C8) carbonylalkyl (C1-C8), (C 1 -C 8) alkoxy (C 1 -C 8) alkyl carbonyloxyalkyl (C 1 -C 8), dialkyl (C 1 -C 8) aminocarbonyloxyalkyl (C 1 -C 8), alkyl (C 1 -C 8) carbonylalkyl (C 1 -C 8), (phenyl or naphthyl) carbonylalkyl (C1-C8), (phenyl or naphthyl) alkyl (C1-C8) carbonylalkyl (C1-C8), aminocarbonyl, (C1-C8) monoalkylaminocarbonyl, dialkyl (C1-C8) aminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, mono (phenyl or naphthyl) aminocarbonylalkyl (C1-C8), ((C 1 -C 8) aminocarbonyl) aminocarbonyl, (C 1 -C 8) aminocarbonylalkyl (C 1 -C 8) alkyl aminocarbonyl, (C 1 -C 8) carboxylaminocarbonyl, (C 1 -C 8) alkoxycarbonylalkyl (C 1 -C 8) alkyl) aminocarbonyl, ((C 1 -C 8) aminoalkyl) aminocarbonyl, (C 1 -C 8) hydroxy (C 1 -C 8) alkylaminocarbonyl, aminocarbonylalkyl (C 1 -C 8), (C 1 -C 8) monoalkyl aminocarbonylalkyl (C 1 -C 8), (C 1 -C 8) dialkyl aminocarbonylalkyl ( C1-C8), mono (phenyl or naphthyl) aminocarbonylalkyl (C1-C8), mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonylalkyl (C 1 -C 8), amidino, hydroxyamidino, guanidino, ureido, mono (C 1 -C 8) alkyl ureido, mono (phenyl or naphthyl) ureido, mono (phenyl or naphthyl) alkyl (C 1 -C 8) ureido, monohaloalkyl (C1-C8) ureido, ((C1-C8) monoalkyl) (mono (phenyl or naphthyl)) ureido, dialkyl (C1-C8) ureido, di (phenyl or naphthyl) ureido, (haloalkyl (C1-C8) carbonyl) ureido, ureidoalkyl (C1-C8), (C1-C8) monoalkyl ureidoalkyl (C1-C8), dialkyl (C1-C8) ureidoalkyl (C1-C8), mono (phenyl or naphthyl) ureidoalkyl (C1-C8), mono (phenyl or naphthyl) alkyl (C1-C8) ureidoalkyl (C1-C8), monohaloalkyl (C1-C8) ureidoalkyl (C1-C8), (haloalkyl) (C 1 -C 8)) (C 1 -C 8 alkyl) ureido (C 1 -C 8) alkyl, (C 1 -C 8 alkoxy) carbonylalkyl (C 1 -C 8)) ureido (C 1 -C 8) alkyl, glycinamide, (C 1 -C 8) monoalkyl glycinamide, aminocarbonylglycinamide, (C 1 -C 8) alkoxy (C 1 -C 8) alkylcarbonyl) glycinamide, (aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, (C 1 -C 8 alkoxy) carbonylalkyl (C 1 -C 8) carbonyl) (C 1 -C 8 alkyl) C8)) glycinamide, (C 1 -C 8 alkoxy) carbonylamino (C 1 -C 8) alkylcarbonyl) glycinamide, (phenyl or naphthyl) carbonylglycinamide, ((phenyl or naphthyl) carbonyl) (C 1 -C 8 alkyl) glycinamide, (mono ( phenyl or naphthyl) alkoxy (C 1 -C 8) aminocarbonyl) glycinamide, (mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, (mono (phenyl or naphthyl) aminocarbonyl) glycinamide, (mono (phenyl or naphthyl) aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, glycinamide (C 1 -C 8) alkyl, alaninamide, (C 1 -C 8) monoalkyl alaninamide, alaninamido (C 1 -C 8) alkyl, 3-15 membered heterocyclyl consists of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and (3-15 membered heterocyclyl consisting of carbon atoms and from one to five selected heteroatoms) from the group consisting of nitrogen, oxygen and sulfur) alkyl (Cl-C8). 3. The compound as described in claim 2, wherein: R4 is -0-, -N (R7) - or -C (R8) -; R5 is an (C2-C8) alkylene chain, - R7 is selected from the group consisting of hydrogen, (C1-C8) alkyl, phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, (C1-C8) alkyl carbonyl, (C 1 -C 8) alkylcarbonylalkyl (C 1 -C 8), (phenyl or naphthyl) alkyl (C 1 -C 8) carbonyl, (phenyl or naphthyl) alkyl (C 1 -C 8) carbonylalkyl (C 1 -C 8), aminocarbonyl, (C 1 -C 8) monoalkylaminocarbonyl, dialkyl (C 1 -C 8) aminocarbonyl, and (C 1 -C 8) alkoxycarbonyl; each R8 is independently selected from the group consisting of hydrogen, (C1-C8) alkyl, phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, hydroxy, (C1-C8) alkoxy, hydroxy (C1-C8) alkyl, (C1-C8) alkoxy (C1-C8) alkyl, amino, (C1-C8) aminoalkyl) amino , dialkyl (C1-C8) amino, alkyl (C1-C8) carbonylamino, cycloalkyl (C3-C10) carbonylamino, cycloalkyl (C3-C10) (C1-C8) alkylcarbonylamino, (C1-C8) alkoxycarbonylamino, (C1-C8) alkyl sulfonylamino, (phenyl or naphthyl) carbonylamino, (C1-C8) alkoxycarbonylalkyl (C1-C8) carbonylamino, (C 1 -C 8 alkylcarbonyl) (C 1 -C 8 alkyl) amino, (phenyl or naphthyl) alkyl (C 1 -C 8) carbonylamino, ((phenyl or naphthyl) alkyl (C 1 -C 8) carbonyl) (alkyl (C1) -C8)) amino, (C 1 -C 8) alkylcarbonylaminoalkyl (C 1 -C 8), (C 3 -C 10) cycloalkylcarbonylamino (C 1 -C 8) alkyl, (C 1 -C 8) alkoxycarbonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) C8) carbonyl) (C 1 -C 8 alkyl) aminoalkyl (C 1 -C 8), (phenyl or naphthyl) C 1 -C 8 alkylcarbonylamino (C 1 -C 8) alkyl, (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (C 1 -C 8) alkylcarbonylamino, ((phenyl or naphthyl) alkyl (C 1 -C 8) carbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (phenyl or naphthyl) sulfonylamino, (C 1 -C 8) alkyl sulfonylamino (C 1 -C 8) alkyl, ureido, (C 1 -C 8) monoalkyl ureido, monohalo (C 1 -C 8) alkyl ureido, dialkyl (C 1 -C 8) ureido, ureido (C 1 -C 8) alkyl, (C 1 -C 8) mono (C 1 -C 8) ureidoalkyl C8), dialkyl (C1-C8) ureidoalkyl (C1-C8), monohaloalkyl (C1-C8) ureidoalkyl (C1-C8), aminoalkyl (C1-C8), monoalkyl (C1-C8) aminoalkyl (C1-C8), dialkyl (C1-C8) (C1-C8) aminoalkyl, (C1-C8) carboxyalkyl, (C1-C8) alkoxycarbonylalkyl (C1-C8), aminocarbonylalkyl (C1-C8), (C1-C8) monoalkylaminocarbonylalkyl (C1-C8) ), and dialkyl (C1-C8) aminocarbonyl-alkyl. 4. The compound as described in claim 3, wherein: R4 is -O-, -Rs is methylene; and Rs is -C (0) - 5. The compound as described in claim 4, wherein: Rla is one or more substituents independently selected from the group consisting of halo, (C 1 -C 8) alkyl, (C 3 -C 10) cycloalkyl, (C 3 -C 10) cycloalkyl aminoalkyl (C1-C8), haloalkyl (C1-C8), hydroxyalkyl (C1-C8), hydroxyalkenyl (C2-C8), hydroxyalkynyl (C2-C8), (hydroxy) (phenyl or naphthyl) alkyl (C1-C8), cyanoalkyl (C 1 -C 8), (C 1 -C 8) haloalkyl carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8) alkoxy (C 1 -C 8) alkyl, (phenyl or naphthyl) (C 1 -C 8) alkoxy (C 1 -C 8) alkyl, (C1-C8) alkylthio (C1-C8) alkyl, hydroxy (C1-C8) alkylthioalkyl (C1-C8), (C1-C8) aminoalkyl, (C1-C8) monoalkylamino (C1-C8) alkyl, (C1-C8) dialkylamino (C1-C8) alkyl, mono (phenyl or naphthyl) aminoalkyl (C1-C8) ), mono (phenyl or naphthyl) alkyl (C1-C8) aminoalkyl (C1-C8), azidoalkyl (C1-C8), monoalkyl (C1-C8) ureidoalkyl (C1-C8), (C1-C8 alkoxy) carbonylalkyl (C1-C8)) ureidoalkyl (C1-C8), hydroxyalkyl (C1-C8) aminoalkyl (C1-C8), (phenyl or naphthyl) oxyalkyl (C1-C8) carbonyloxyalkyl (C1-C8), (phenyl or naphthyl) alkoxy (C 1 -C 8) C 1 -C 8 alkylcarbonyloxyalkyl (C 1 -C 8) alkyl (C 1 -C 8) carbonylalkyl (C 1 -C 8), (C 1 -C 8) alkoxycarbonyl, (C 1 -C 8) alkoxycarbonylalkyl (C 1 -C 8) ), and (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (C 1 -C 8) alkyl, - is one more substituents independently selected from the group consisting of hydrogen and halo, - R3 is phenyl optionally substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, (C1-C8) alkyl, (C1-C8) alkoxy, hydroxy (C1-C8) alkoxy ), (C1-C8) haloalkyl, formyl, nitro, cyano, (C1-C8) aminoalkoxy, (C3-C10) cycloalkyl, (C3-C10) cycloalkyl (C1-C8) aminoalkyl, (phenyl or naphthyl) alkyl (C1) -C8) , hydroxy (C1-C8) alkyl, ((C1-C8) amino) alkyl (phenyl or naphthyl) alkyl (C1-C8), alkoxy (C1-C8) alkyl (C 1 -C 8), amino, (C 1 -C 8) aminoalkyl, dialkyl (C 1 -C 8) amino, mono (phenyl or naphthyl) alkyl (C 1 -C 8) amino, alkyl (C 1 -C 8) carbonylamino, alkenyl (C 2 -) C8) carbonylamino, (C3-C10) cycloalkyl carbonylamino, (phenyl or naphthyl) carbonylamino, (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylamino, (C1-C8) haloalkyl carbonylamino, (C1-C8) alkoxy carbonylaminoalkyl (C1 -C8), (C1-C8) alkoxycarbonylalkyl (C 1 -C 8) carbonylamino, (C 1 -C 8 alkylcarbonyl) (C 1 -C 8 alkyl) amino, (C 1 -C 8) alkyl sulfonylamino, amino (C 1 -C 8) alkyl, (C 1 -C 8) monoalkyl aminoalkyl (C 1 -C 8) -C8), dialkyl (C1-C8) aminoalkyl (C1-C8), mono (phenyl or naphthyl) aminoalkyl (C1-C8), mono (phenyl or naphthyl) alkyl (C1-C8) aminoalkyl (C1-C8), alkyl (C 1 -C 8) carbonylamino (C 1 -C 8) alkyl, (phenyl or naphthyl) carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) carbonyl) (alkyl) (C1-C8)) (C1-C8) aminoalkyl, (C1-C8) cycloalkylalkyl) amino (C1-C8) alkyl, (C1-C8) alkoxycarbonylamino (C1-C8) alkyl, (C1-C8) alkoxycarbonylalkyl (C1 -C8) carbonylaminoalkyl (C1-C8), (C1-C8 alkoxy) carbonyl) (C1-C8) alkyl) aminoalkyl (C1-C8), (C1-C8) alkyl sulfonylamino (C1-C8) alkyl, (alkyl) (C 1 -C 8) sulfonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (phenyl or naphthyl) sulfonylamino (C 1 -C 8) alkyl, ((phenyl or naphthyl) sulfonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) aminoalkyl (C 1 -) C8), carboxy, (C1-C8) alkoxycarbonyl, (C1-C8) alkylcarbonyl, (hydroxy (C1-C8) alkoxycarbonyl, aminocarbonyl, (C1-C8) monoalkylaminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, ( aminocarbonylalkyl (C1-C8)) aminocarbonyl, ((C1-C8) aminoalkyl) aminocarbonyl, (hydroxy (C1-C8) alkyl) aminocarbonyl, dialkyl (C1-C8) aminocarbonylalkyl (C1-C8), hydroxyamidino, ureido, monoalkyl (C1-C8) ureido, mono (phenyl or naphthyl) ureido, mono (phenyl or naphthyl) alkyl (C1-C8) ureido, (mono (C1-C8) alkyl) (mono (phenyl or naphthyl)) ureido, (haloalkyl ( C1-C8) carbonyl) ureido, ureidoalkyl (C1-C8), monoalkyl (C1-C8) ureidoalkyl (C1-C8), dialkyl (C1-C8) ureidoalkyl (C1-C8), mono (phenyl or naphthyl) ureidoalkyl (C1 -C8), mono (phenyl or naphthyl) alkyl (C1-C8) ureidoalkyl (C1-C8), monohaloalkyl (C1-C8) ureidoalkyl (C1-C8), (haloalkyl (C1-C8)) (C1-C8 alkyl) )) ureidoalkyl (C1-C8), (C1-C8alkoxy) carbonylalkyl (C1-C8)) ureidoalkyl (C1-C8), glycinamide, (C1-C8) monoalkyl glycinamide, aminocarbonylglycinamido, (C1-C8alkoxy) alkyl (C 1 -C 8) carbonyl) glycinamide, (aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, (C 1 -C 8 alkoxy) carbonylalkyl (C 1 -C 8) carbonyl) (C 1 -C 8 alkyl) glycinamide, (alkoxy) C1-C8) carbonylaminoalkyl (C1-C8) carbonyl) glycinamide, (phenyl or naphthyl) carbonylglycinamide, ((phenyl or naphthyl) carbonyl) (C1-C8 alkyl) glycinamide, (mono (fe nil or naphthyl) alkyl (C 1 -C 8) aminocarbonyl) glycinamide, (mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, (mono (phenyl or naphthyl) aminocarbonyl) glycinamide, (mono (phenyl or naphthyl) aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, alaninamide, 3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur , and (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (C 1 -C 8) alkyl. 6. The compound as described in claim 5, selected from the group consisting of the following compounds: (2 S) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-f-luorobenzyl) piperazine , 1- ((phenoxy) methyl) carbonyl-2-ethyl-4- (4-f luorobenzyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chloro-enoxy) methyl) carbonyl-2-ethylpiperazine; 4- (4-fluorobenzyl) -1- ((4-chloro-enoxy) 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-f luorobenzyl) piperazine, -1- (4-chlorofenoxi) methyl) carbonyl-2 - (2- (methyl) amino) ethyl) -4- (4-f luorobenzyl) piperazine; 1- (4-chloro-enoxy) methyl) carbonyl-2- (2- (2-hydroxyethyl) amino) ethyl) -4- (4-f luorobenzyl) iperazine; 4- (4-fluorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl-3- ((4-chloro-enoxy) -methyl) -carbonyl) oxy) methyl-5-methylpiperazine; 4- (4-fluorobenzyl) -1- (4-chlorophenoxy) methyl) carbonyl-3- (ethoxycarbonyl) iperazine; 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-f-luorobenzyl) -1- (4-chloro-enoxy) -methyl) -carbonyl-3- (2- (methoxy) -ethyl) -piperazine; 4- (4-fluorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl-3- (2-hydroxy-2- (4-methyl-phenyl) -ethyl) -piperazine; 4- (4-fluorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl-3- (2-hydroxypropyl) piperazine; 4- (4-fluorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl-3 - (2-hydroxybut -4 -inyl) iperazine; 4- (4-fluorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl-5- (2-hydroxy-2-methylpropyl) piperazine; 4- (4-fluorobenzyl) -1- (4-chloro-enoxy) -methyl) -carbonyl-3- (2-hydroxyethyl) piperazine; 1- (4-chloro-enoxy) methyl) carbonyl -3- (2- (2-hydroxyethyl) amino) ethyl) -4- (4-f luorobenzyl) piperazin, - (cis) -4- (4-f luorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl -2,3-dimethylpiperazine; (2S, 5R) -1- (4-chloro-3,5-dimethoxyphenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (2S, 5S) -4- (4-f luorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl -2,5-dimethylpiperazine; (2R, 5S) -4- (4-f luorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl-2-methyl-5- (2-methylthio) ethylpiperazine; (2R, 5R) -4- (4-f luorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl-2-methyl-5- (benzyloxy) methyl-piperazin; (2R, 5R) -1- (4-chlorophenoxy) methyl) carbonyl-2-methyl-4 - (4-fluorobenzyl) -5- ((2-hydroxyethyl) thio) methyl) piperazine: 4- (4-fluorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl-2- (N '- (ethoxycarbonylmethyl) ureido) methyl) piperazine; (2R, 5S) -1- (4-chloro-enoxy) methyl) carbonyl-2-methyl-5 - (amino) carbonyloxy) methyl-4- (4-f luorobenzyl) piperazine; 4- (4-fluorobenzyl) -1- (4-chlorophenoxy) methyl) carbonyl-3- (acetyl) methyl) piperazine; (2R, 5R) -4- (4-f luorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl-2-methyl-5- (l-hydroxy-1- (phenyl) methyl) iperazine; (2R, 5R) -4- (4-f luorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl-2-methyl-5- (1-hydroxybu il) iperazine; (2R, 5S) -1- (4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-f-luorobenzyl) -5- (diethylamino) methyl) piperazine; (2R, 5S) -1- (4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-f-luorobenzyl) -5- (dimethylamino) methyl) piperazine; (2R, 5S) -1- (4-chlorophenoxy) methyl) carbonyl-2-methyl-4 - (4-fluorobenzyl) -5- ((cyclopropyl) amino) methyl) iperazine; (2R, 5S) -1- (4-chlorophenoxy) methyl) carbonyl-2-methyl-4- (4-f-luorobenzyl) -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-f luorobenzyl) piperazine; (cis) -4- (4-f luorobenzyl) -1- (4-chloro-enoxy) methyl) carbonyl -2,6-dimethylpiperazine; 1- (phenoxy) methyl) carbonyl-2-methyl-4- (4-f luorobenzyl) iperazine, 1- (2 - (acetylamino) phenoxy) methyl) carbonyl-2-methyl-4 - (4-fluorobenzyl) iperazine; 1- (4-chloro-enoxy) -me il) carbonyl-2- (2-hydroxypropyl -4 - (4-f luorobenzyl) iperazine; 1- (4-chlorofenoxi) methyl) carbonyl-2- (2-hydroxybutyl) -3- -enyl) -4- (4-f luorobenzyl) piperazine, -l (4-chlorophenoxy) methyl) carbonyl-3-trifluoromethyl-4- (4-f-luorobenzyl) piperazin; and (trans) -1- (4-chloro-2- (4- (2,5-di (trifluoromethyl) f enylcarbonyl) -piperazin-l-yl) methyl) phenoxy) methyl) carbonyl -2,5- dimethyl -4- (4-f luorobenzyl) iperazine. 7. The compound as described in claim 5, wherein: Rla is one or more substituents independently selected from the group consisting of (C 1 -C 8) alkyl, (C 3 -C 10) cycloalkyl, (C 1 -C 8) hydroxyalkyl, hydroxyalkenyl ( C2-C8), cyano (C1-C8) alkyl, (C1-C8) alkoxy (C1-C8) alkyl, (C1-C8) monoalkylamino (C1-C8) alkyl, (C1-C8) azidoalkyl, (C1-C8) monoalkyl ) ureidoalkyl (C1-C8), (phenyl or naphthyl) oxyalkyl (C1-C8) carbonyloxyalkyl (C1-C8), and (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (C 1 -C 8) alkyl, - R 2 is one or more substituents independently selected from the group consists of hydrogen, chlorine or fluoro; R3 is phenyl substituted by one or more substituents independently selected from the group consisting of hydroxy, halo, (C1-C8) alkyl, (C1-C8) alkoxy, formyl, nitro, cyano, (C1-C8) aminoalkoxy, (C3) cycloalkyl -C10) aminoalkyl (C1-C8), hydroxyalkyl (C1-C8), ((C1-C8) monoalkylamino) (phenyl or naphthyl) (C1-C8) alkyl, (C1-C8) alkoxy (C1-C8) alkyl, amino, (C1-C8) aminoalkyl, (C1-C8) dialkylamino, mono (phenyl or naphthyl) alkyl (C1-C8) amino, (C1-C8) alkylcarbonylamino, (C2-C8) alkenyl carbonylamino, (C3-C10) cycloalkyl carbonylamino, (phenyl or naphthyl) carbonylamino, (3-15 membered heterocyclyl consisting of carbon and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylamino, haloalkyl (C 1 -C 8) carbonylamino, alkoxy (C 1 -C 8) carbonylaminoalkyl (C 1 -C 8), alkoxy (C 1 -C 8) carbonylalkyl ( C1-C8) carbonylamino, (C1-C8) alkyl sulfonylamino, amino (C1-C8) alkyl, (C1-C8) monoalkyl amino (C1-C8) alkyl, (C1-C8) dialkylamino (C1-C8) alkyl, mono (phenyl) or naphthyl) (C 1 -C 8) alkyl amino (C 1 -C 8) alkyl, (C 1 -C 8) alkyl carbonylamino (C 1 -C 8) alkyl, (phenyl or naphthyl) carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) carbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (C 1 -C 8) cycloalkylalkyl) (C 1 -C 8) -alkoxy, (C 1 -C 8) -alkoxycarbonylalkyl (C 1 -C 8) alkylcarbonylamino (C 1 -C 8) alkyl, (C 1 -C 8) alkylsulfonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) sulfonyl) (alkyl) (C 1 -C 8)) (C 1 -C 8) aminoalkyl, (phenyl or naphthyl) sulfonylamino (C 1 -C 8) alkyl, ((phenyl or naphthyl) sulfonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, carboxy, (C 1 -C 8) alkoxycarbonyl, (C 1 -C 8) alkylcarbonyl, (hydroxy (C 1 -C 8) alkoxycarbonyl, aminocarbonyl, (C 1 -C 8) monoalkylaminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, (aminocarbonylalkyl (C 1 -C 8) )) aminocarbonyl, ((C 1 -C 8) aminoalkyl) aminocarbonyl, (C 1 -C 8) hydroxy (C 1 -C 8) aminocarbonyl, hydroxyamidino, ureido, mono (C 1 -C 8) alkylidene, mono (phenyl or naphthyl) ureido, mono (phenyl or naphthyl) alkyl (C1-C8) ureido, ((C 1 -C 8) monoalkyl (mono (phenyl or naphthyl)) ureido, (haloalkyl) (C1-C8) carbonyl) ureido, ureidoalkyl (C1-C8), monoalkyl (C1-C8) ureidoalkyl (C1-C8), dialkyl (C1-C8) ureidoalkyl (C1-C8), mono (phenyl or naphthyl) ureidoalkyl (C1-C8), mono (phenyl or naphthyl) alkyl (C1-C8) ureidoalkyl (C1-C8), monohaloalkyl (C1-C8) ureidoalkyl (C1-C8), (haloalkyl (C1-C8)) (alkyl (C1-C8)) ureidoalkyl (C1-C8), (C1-C8alkoxy) carbonylalkyl (C 1 -C 8)) ureido (C 1 -C 8) alkyl, glycinamide, (C 1 -C 8) monoalkyl glycinamide, aminocarbonylglycinamido, (C 1 -C 8) alkoxy (C 1 -C 8) alkylcarbonyl) glycinamide, (C 1 -C 8 alkoxy) carbonylamino (C1-C8) carbonyl) glycinamide, (phenyl or naphthyl) carbonylglycinamide, ((phenyl or naphthyl) carbonyl) (alkyl) (C 1 -C 8)) glycinamide, (mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonyl) _ (C 1 -C 8 alkyl) glycinamide, (mono (phenyl or naphthyl) aminocarbonyl) glycinamide, (mono (phenyl or naphthyl) aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, alaninamide, 3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, and (heterocyclyl 3-15 members consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (C 1 -C 8) alkyl. 8. The compound as described in the 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) piperazine, 4- (4-fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2-ethylpiperazine , - (2R) -4- (4-f luorobenzyl) -1- ((4-chlorofenoxi) methyl) carbonyl-2-propylpiperazine, - (2S) -4- (4-f luorobenzyl) -1- (( 4-chloro enoxy) methyl) carbonyl-2-propylpiperazine, 4- (4-fluorobenzyl) -1- (((4-chlorophenoxy) me il) carbonyl) -spiro [cyclopropane-1,2'-piperazine], - 1- ((4-chlorophenoxy) methyl) carbonyl-2-hydroxymethyl-4- (4-fluorobenzyl) piperazine, -4- (4-fluorobenzyl) -1- ((4-chlorofenoxy) methyl) carbonyl-2- ( 2- (methoxy) ethyl) piperazine; l- (4-chlorophenoxy) methyl) carbonyl -2- (2- ((2-methylpropyl) amino) ethyl) -4- (4-f luorobenzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-3-methyl-4- (4-f-luorobenzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-4- (4-fluorobenzyl) -5-methylpiperazine; (2R) -1- ((4-chlorophenoxy) methyl) carbonyl-3-methyl-4- (4-fluorobenzyl) piperazine; (2 S) -1- ((4-chlorophenoxy) methyl) carbonyl-3-methyl-4- (4-f luorobenzyl) piperazine, 4- (4-fluorobenzyl) -1- ((4-chlorofenoxi) methyl) carbonyl-3- (hydroxymethyl) iperazine; 4- (4-fluorobenzyl) -1- ((4-chloro-enoxy) methyl) carbonyl-3- (2-hydroxyethyl) piperazine; 4- (4-fluorobenzyl) -1- ((4-chlorofenoxyl) met il) carbonyl-2- ((methyl) ureido) methyl) piperazine, - (2R, 3R) -4- (4-f luorobenzyl) - 1- ((4-chloro-enoxy) -methyl) -carbonyl-2,3-dimethyl-piperazine, - (cis) -1- ((4-chloro-enoxy) -methyl) -carbonyl -3,5-dimethyl-4- (4-fluorobenzyl) piperazine; 4- (4-f luorobenzyl) -1- ((4-chloro-enoxy) methyl) carbonyl-2- (2- (((4-chlorophenoxy) -methyl) carbonyl) oxy) ethyl-5-methylpiperazine, (2R, 5R) -1- ((4-chlorophenoxy) methyl) carbonyl-2-methyl-4 - (4-f luorobenzyl) -5- ((hydroxy) methyl) piperazine; (2R, 5R) - ((4-f luorobenzyl) -1- ((4-chlorofenoxi) methyl) carbonyl-2-methyl-5- ((methoxy) -methyl) piperazine, - (2R, 5S) -4 - (4-f luorobenzyl) -1- ((4-chloro-enoxy) methyl) carbonyl-2-methyl-5- (1-methylethyl) piperazine; (2R, 5R) -4- (4-fluorobenzyl) -1- ((4-chloro-enoxy) methyl) carbonyl-2-methyl-5- (1-hydroxyethyl) piperazine; (2R, 5R) -4- (4-f luorobenzyl) -1- ((4-chlorofenoxy) methyl) carbonyl -2-methyl-5- (1-hydroxyprop-3-yl) piperazine; (2R, 5S) -1- ((4-chlorophenoxy) methyl) carbonyl -2-methyl-4 - (4-f luorobenzyl) - 5- ((cyano) methyl) piperazine; (2R, 5R) -l - ((4- chloro or phenoxy) 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; (3S, 5S) -4- (4-f luorobenzyl) -1- ((4-chloro-enoxy) methyl) carbonyl-3,5-dimethylpiperazine; 1- ((4-chloro-3-n-trofenoxy) ) methyl) carbonyl-2-methyl-4 - (4-fluorobenzyl) ) piperazine; (trans) -1- ((4-chloro-2-methylphonoxy) methyl) carbonyl -2,5-dimethyl-4 - (4-f luorobenzyl) iperazine; (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-chloro-3-nitrophenoxy) methyl) carbonyl -2-methyl-4- (4-fluorobenzyl) iperazine; (trans) -1- ((4-chloro-2- (benzylamino) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-Chloro-2- ((1-methyl-1-buyl) -amino) -phenoxy) -methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) -piperazine; (trans) -1- ((4-chloro-2- (iso-propylcarbonylamino) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (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-f luorobenzyl) piperazine, - (trans) -1- ((4-chloro-2 - ((cyclopropylmethyl) aminomethyl) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (phenylaminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (acetylaminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((methylamino) (phenyl) methyl) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (1- (phenylsulfonyl) (methyl) aminoethyl) phenoxy) -methyl) carbonyl-2, 5-dimethyl-4- (4-f-luorobenzyl) piperazine: (trans ) -1- ((4-chloro-2- (1- (acetyl) (methyl) aminoethyl) phenoxy) -methyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (1- (N-methyl-N'-ethylureido) -ethyl) phenoxy) methyl) -carbonyl-2,5-dimethyl-4 - (4-f-luorobenzyl) ) piperazine; (trans) -l- ((4-chloro-2 - (l- ((methyl) (ethyl) amino) ethyl) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-f-luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (1- (dimethylamino) and yl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) iperazine; (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) iperazine; 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) iperazine; (trans) -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) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((3-Forylphenoxy) 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-methyl-phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((5-nitro-2-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (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, - (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) piperazine, - (trans) -1- ((2-acetyl-4 , 5-dimethyl phenoxy) 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) -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-nitrophenoxy) 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-methyl-enoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; 1- ((4-chlorophenoxy) methyl) carbonyl-2- (2-azidoethyl) -4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (f -imido) phenoxy) methyl) carbonyl -2,5-dimethyl-4 - (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (maleimido) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((4-chloro-2- ((4- (benzylcarbonyl) piperazin-1-yl) methyl) phenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-f-luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((4- ((2,3,4-trifluorofenyl) aminocarbonyl) -piperazin-l-yl) methyl) phenoxy) me il) carbonyl -2 , 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2 - ((4 - ((2-f luorofenyl) aminocarbonyl) piperazin-1-yl) methyl) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (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) 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- ((N1- (3-me hoxyphenyl) ureido) phenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; ) -1- ((4-chloro-2- ((N1 - (methoxycarbonylmethylcarbonyl) -N '- (methyl) glycinamide) phenoxy) methyl) carbonyl -2,5-dimethyl-4 - (4-fluorobenzyl) piperazine; trans) -1- ((4-chloro-2- ((N '- (2-methoxycarbonylethyl) carbonyl-N' - (methyl) glycinamide) phenoxy) 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-Fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((N '- (3-trif luoromethyl-4-f luorofenyl) carbonyl-N 1 - (methyl) glycinamide) phenoxy) methyl ) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((N 1 - (4-methylbenzyl) aminocarbonyl-N '- (methyl) glycinamide) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((N1 - (3-chlorophenyl) carbonyl-N '- (methyl) glycinamide) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4- f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((N1 - (4-f luorobenzyl) aminocarbonyl-N '- (methyl) glycinamide) phenoxy) methyl) carbonyl -2,5-dimethyl -4- (4-f luorobenzyl) piperazine, - (trans) -1- ((4-chloro-2 - (N 1 - (2-yodofenylcarbonyl) glycinamide) -phenoxy) methyl) carbonyl-2, 5-dimethyl -4- (4-fluorobenzyl) piperazine, - (trans) -1 - ((4-chloro-2 - (N '- (2,3-dif luorofenylcarbonyl) glycinamide) -phenoxy) -methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N 1 - ((4-f enoxyphenyl) aminocarbonyl) -glycinamido) phenoxy) -methyl) carbonyl -2, 5-dimethyl-4- (4-f-luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N1- (2,4-difluorophenylcarbonyl) -glycinamido) -phenoxy) methyl) - carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((2-iodophenyl) rbonyl) 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) 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; (2S) -1- ((4-chloro-2- (ureido) phenoxy) methyl) carbonyl -2-methyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((2,5-di (trifluoromethyl) phenyl) carbonyl-aminomethyl) -phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; and (trans) -1- ((4-chloro-2- (N1 - (2- (phenyl) cyclopropyl) ureidomethyl) -phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine. 9. The compound as described in claim 7, wherein: Rla is one or more substituents independently selected from the group consisting of (C 1 -C 8) alkyl and (C 1 -C 8) hydroxyalkyl; R2 is one or more substituents independently selected from the group consisting of hydrogen, chloro or fluoro; R3 is phenyl substituted by one or more substituents independently selected from the group consisting of halo, (C1-C8) alkyl, (C1-C8) alkoxy, formyl, nitro, (C3-C10) cycloalkyl (C1-C8) aminoalkyl, hydroxyalkyl (C1-C8), amino, alkyl (C 1 -C 8) carbonylamino, haloalkyl (C 1 -C 8) carbonylamino, alkoxy (C 1 -C 8) alkyl (C 1 -C 8) carbonylamino, alkoxy (C 1 -C 8) carbonylalkyl (C 1 -C 8) carbonylamino, alkyl (C1-C8) sulfonylamino, (C1-C8) aminoalkyl, (C1-C8) monoalkyl amino (C1-C8) alkyl, (C1-C8) dialkylamino (C1-C8) alkyl, (C 1 -C 8 alkyl) sulfonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (C 1 -C 8) alkylcarbonyl, aminocarbonyl, (C 1 -C 8) aminocarbonyl monoalkyl, mono (phenyl or naphthyl) aminocarbonyl, (aminocarbonylalkyl (C1-C8)) aminocarbonyl, (aminoalkyl) (C1-C8)) aminocarbonyl, hydroxyamidino, ureido, (haloalkyl) - (C 1 -C 8) carbonyl) ureido, ureido (C 1 -C 8) alkyl, glycinamide, (C 1 -C 8) monoalkyl glycinamide, aminocarbonylglycinamide, (C 1 -C 8) alkoxy (C 1 -C 8) alkylcarbonyl) glycinamide, (aminocarbonyl) (C1-C8 alkyl) glycinamide, (C 1 -C 8 alkoxy) carbonylaminoalguyl (C 1 -C 8) carbonyl) glycinamide, alaninamide, and (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur ) alkyl (Cl-C8). 10. The compound as described in 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) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (2R, 5S) -1- ((4-chloro-2- (aminocarbonyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (2S, 5R) -l - ((4-bromo-3,5-dimethoxyphenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (2R, 5S) -1- ((3-hydroxy-5-methylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (2S, 5R) -1- ((4-nitro-3-formylphenoxy) -me il) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) 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) carbonyl-2,5-dimethylpiperazine; (2R, 5S) -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) iperazine; (2R, 5S) -1- (4-chloro-3,5-dimethoxyphenoxy) methyl) carbonyl-2, 5-dimethyl-4- ((4-fluorobenzyl) piperazine; (2R, 5S) -4- (4- fluorobenzyl) -1- ((4-chlorophenoxy) methyl) carbonyl-2- (2-hydroxyethyl) -5-methylpiperazine; (2R, 6R) -4- (4-Fluorobenzyl) -1- ((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, - (2R, 5S) -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-fluorobenzylperazine, - (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-f luorobenzyl) -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) ethylcarbonylamino) -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- (bromomethyl carbonylamino) phenoxy) -methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) iperazine; (2R) -1- ((4-chloro-2- (glycinamide) phenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) ) piperazine; (trans) -1- ((4-chloro-2- ((N '-methylgli cinnamido) 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) glycinamide) phenoxy) -methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperaz ina; (trans) -1- ((4-chloro-2- ((aminocarbonyl) (methyl) glycinamide) -phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (N 1 -ethylurio) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (ethylcarbonylamino) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2-amino-5-nitro-enoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-fluorobenzyl) piperazinylhydrochloride salt; (trans) -1- ((4-chloro-2- (((ethyl) amino) methyl) f-enoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine, (trans) - 1- ((4-chloro-2- (((diethyl) amino) methyl) phenoxy) -methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (((cyclopropyl) amino) methyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((4-chloro-2- (((dimethyl) amino) methyl) phenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) iperazine, (trans) - 1 - ((4-chloro-2 - (((methyl) amino) methyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((amino) methyl) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2 - ((4-methylpiperazin-1-yl) methyl) phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-f-luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((piperazin-1-yl) ethyl) phenoxy) -methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (trans) -1- ((4-chloro-2- (ethylaminomethyl) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) 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) 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; (2 R, 5 S) - 1 - ((4-Cl-2 - ((p iperaz in-1-yl) methyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) ) piperazine, - (trans) -1- ((4-chloro-2- ((4-l-butoxycarbonylpiperazin-1-yl) ethyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f) luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (imidazol-1-ylmethyl) f enoxi) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine, - (rans) -1 - ((4-chloro-2- (1- (imidazol-1-yl) and yl) phenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (triazol-1-ylmethyl) f-enoxy) methyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (tetrazol-1-ylmethyl) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((morpholin-4-yl) met yl) phenoxy) methyl) -carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (2R) -1- ((4-chloro-2-arainocarbonylf-enoxy) methyl) carbonyl-2-methyl-4- (4-f-luorobenzyl) -perazine; 1- ((4-chloro-2-formylphenoxy) methyl) carbonyl-2-methyl-4- (4-fluorobenzyl) piperazine; (2R, 5S) -1- ((4-chloro-2-formylphenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (2R) -1- ((4-chloro-2-formylphenoxy) -yl) -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-fiuorobenzyl) piperazine; (trans) -1- ((4-chloro-2- ((4-aminocarbonylphenyl) aminocarbonyl) -phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (hydroxdino) 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-4- (4-fluorobenzyl) iperazine; (trans) - 1- ((4-chloro-2- (N 1 - (methoxymethylcarbonyl) glycinamide) -phenoxy) methyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine, -y (trans) -1- ( (4-chloro-2- (N 1 - (ethoxycarbonylaminocarbonyl) -glycinaraido) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine. 11. The compound as described in the claim 9, wherein R2 is 4-fluoro and R3 is phenyl substituted at the 4-position with chlorine and at the 2-position by aminocarbonyl, ureido, or glycinamide; specifically, the compound is selected from the group consisting of the following compounds: (2R, 5S) -l- ((4-chloro-2- (aminocarbonyl) phenoxy) methyl) carbonyl-2, 5-dimethyl-4- (4 -f luorobenzyl) piperazine; (trans) -1- ((4-chloro-2- (glycinamide) phenoxy) methyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (2 R) -1- ((4-Cl-2-gold- (ureido) f-enoxy) methyl) carbonyl-2-methyl-4- (4-f-luorobenzyl) -piperazine; (trans) -1- ((4-chloro-2- (ureido) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) iperazine; (2R, 5S) -1- ((4-chloro-2- (ureido) phenoxy) methyl) carbonyl -2,5-dimethyl-4- (4-f luorobenzyl) piperazine; and (2R, 5S) -l- ((4-chloro-2- (glycinamido) -phenoxy) methyl) carbonyl -2,5-d-imethyl-4- (4-fluorobenzyl) piperazine. 12. The compound as described in claim 3, wherein: R 4 is -N (R 7) -; Rs is methylene; Rs is -C (0) -, - and R7 is selected from the group consisting of hydrogen, (C1-C8) alkyl, phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, (C1-C8) alkyl carbonyl, alkyl (C1-C8) carbonylalkyl (C1-C8), (phenyl or naphthyl) alkyl (C1-C8) carbonyl, (phenyl or naphthyl) alkyl (C1-C8) carbonylalkyl (C 1 -C 8), aminocarbonyl, (C 1 -C 8) monoalkylaminocarbonyl, dialkyl (C 1 -C 8) aminocarbonyl, and (C 1 -C 8) alkoxycarbonyl. 13. The compound as described in claim 12, wherein: Rla is one or more substituents independently selected from the group consisting of halo, (C 1 -C 8) alkyl, (C 3 -C 10) cycloalkyl, (C 3 -C 10) cycloalkyl aminoalkyl (C1-C8), haloalkyl (C1-C8), hydroxyalkyl (C1-C8), hydroxyalkenyl (C2-C8), hydroxyalkynyl (C2-C8), (hydroxy) (phenyl or naphthyl) alkyl (C1-C8), cyanoalkyl (C 1 -C 8), (C 1 -C 8) haloalkyl carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8) alkoxy (C 1 -C 8) alkyl, (phenyl or naphthyl) (C 1 -C 8) alkoxy (C 1 -C 8) alkyl, (C1-C8) alkylthio (C1-C8) alkyl, (C1-C8) hydroxyalkyl (C1-C8) alkyl, (C1-C8) aminoalkyl, (C1-C8) monoalkylamino (C1-C8) alkyl, 'dialkyl (C1 -C8) aminoalkyl (C1-C8), mono (phenyl or naphthyl) aminoalkyl (C1-C8), mono (phenyl or naphthyl) alkyl (C1-C8) aminoalkyl (C1-C8), azidoalkyl (C1-C8), monoalkyl (C1-C8) ureidoalkyl (C1-C8), (C1-C8 alkoxy) carbonylalkyl (C1-C8)) ureidoalkyl (C1-C8), (C 1 -C 8) hydroxyalkyl (C 1 -C 8) alkyl, (phenyl or naphthyl) oxyalkyl (C 1 -C 8) carbonyloxyalkyl (C 1 -C 8), (phenyl or naphthyl) alkoxy (C 1 -C 8) alkyl (C 1 -C 8) carbonyloxyalkyl (C1-C8), (C1-C8) alkylcarbonylalkyl (C1-C8), # (C1-C8) alkoxycarbonyl, (C1-C8) alkoxycarbonylalkyl (C1-C8), and (3-15 membered heterocyclyl which consists of carbon atoms and one to five heteroatoms selected from the group of nitrogen, oxygen and sulfur) (C 1 -C 8) alkyl, - R 2 is one or more substituents independently selected from the group consisting of hydrogen and halo; R3 is phenyl optionally substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, (C1-C8) alkyl, (C1-C8) alkoxy, hydroxy (C1-C8) alkoxy, halo (C1-C8) alkyl , formyl, nitro, cyano, (C1-C8) aminoalkoxy, (C3-C10) cycloalkyl, (C3-C10) cycloalkyl (C1-C8) aminoalkyl, (phenyl or naphthyl) (C1-C8) alkyl, hydroxyalkyl (C1- C8), ((C1-C8) monoalkylamino) (phenyl or naphthyl) (C1-C8) alkyl, (C1-C8) alkoxy (C1-C8) alkyl, amino, (C1-C8) aminoalkyl, dialkyl (C1 -C8) amino, mono (phenyl or naphthyl) alkyl (C1-C8) amino, alkyl (C1-C8) carbonylamino, (C2-C8) alkenyl carbonylamino, cycloalkyl (C3 -CIO) carbonylamino, (phenyl or naphthyl) carbonylamino, (3-15 membered heterocyclyl consisting of carbon atoms and one to five heteroatoms selected from the group of nitrogen, oxygen, and sulfur) carbonylamino, haloalkyl (C 1 -C 8) carbonylamino, (C 1 -C 8) alkoxy (C 1 -C 8) alkyl carbonylamino, (C 1 -C 8) alkoxy carbonylalkyl (C 1 -C 8) carbonylamino, (alkyl) (C 1 -C 8) carbonyl) (C 1 -C 8 alkyl) amino, (C 1 -C 8) alkyl sulfonylamino, (C 1 -C 8) aminoalkyl, (C 1 -C 8) monoalkyl (C 1 -C 8) alkyl, (C 1 -C 8) dialkyl ) aminoalkyl (C1-C8), mono (phenyl or naphthyl) aminoalkyl (C1-C8), mono (phenyl or naphthyl) alkyl (C1-C8) __ aminoalkyl (C1-C8), alkyl (C 1 -C 8) carbonylamino (C 1 -C 8) alkyl, (phenyl or naphthyl) carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) carbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (cycloalkylalkyl) (C1-C8)) (C1-C8) aminoalkyl, (C1-C8) alkoxycarbonylaminoalkyl (C1-C8), (C1-C8) alkoxycarbonylalkyl (C1-C8) carbonylaminoalkyl (C1-C8), (C1-6alkoxy) C8) carbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (C 1 -C 8) alkyl sulfonylamino (C 1 -C 8) alkyl, (alkyl) (C 1 -C 8) sulfonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (phenyl or naphthyl) sulfonylamino (C 1 -C 8) alkyl, ((phenyl or naphthyl) sulfonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group of nitrogen, oxygen and sulfur), amino (C 1 -C 8) alkyl ), carboxy, (C 1 -C 8) alkoxycarbonyl, (C 1 -C 8) alkylcarbonyl, (hydroxy (C 1 -C 8) alkoxycarbonyl, aminocarbonyl, (C 1 -C 8) monoalkylaminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, (aminocarbonylalkyl) (C 1 -C 8)) aminocarbonyl, (C 1 -C 8) aminocarbonyl aminocarbonyl, (C 1 -C 8 hydroxyalkyl) aminocarbonyl, dialkyl (C 1 -C 8) aminocarbonylalkyl (C 1 -C 8), hydroxyamidino, ureido, monoalkyl (C1-C8) ureido, mono (phenyl or naphthyl) ureido, mono (phenyl or naphthyl) alkyl (C1-C8) ureido, (mono (C1-C8) alkyl) (mono (phenyl or naphthyl)) ureido, (haloalkyl ( C1-C8) carbonyl) ureido, ureidoalkyl (C1-C8), (C1-C8) monoalkyl ureidoalkyl (C1-C8), dialkyl (C1-C8) ureidoalkyl (C1-C8), mono (phenyl or naphthyl) ureidoalkyl (C1-C8), mono (phenyl or naphthyl) alkyl (C1-C8) ureidoalkyl (C1-C8), monohaloalkyl (C1-C8) ureidoalkyl (C1-C8), (haloalkyl (C1-C8)) (alkyl (C1-C8)) ureidoalkyl (C1-C8), (C1-C8 alkoxy) carbonylalkyl (C 1 -C 8)) ureido (C 1 -C 8) alkyl, glycinamide, (C 1 -C 8) monoalkyl glycinamide, aminocarbonylglycinamide, (C 1 -C 8) alkoxy (C 1 -C 8) alkylcarbonyl) glycinamide, (aminocarbonyl) (C 1 -C 8 alkyl) C8)) glycinamide, (C 1 -C 8 alkoxy) carbonylalkyl (C 1 -C 8) carbonyl) (C 1 -C 8 alkyl) glycinamide, (C 1 -C 8 alkoxy) carbonylamino (C 1 -C 8) alkylcarbonyl) glycinamide, (phenyl or naphthyl) carbonylglycinamido, ((phenyl or naph il) carbonyl) (C 1 -C 8 alkyl) glycinamide, (mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonyl) glycinamide, (mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, (mono (phenyl or naphthyl) aminocarbonyl) glycinamide , (mono (phenyl or naphthyl) aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, alaninamide, 3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group of nitrogen, oxygen and sulfur, and (3-15 membered heterocyclyl consisting of carbon atoms and one to five heteroatoms selected from the group of nitrogen, oxygen and sulfur) (C 1 -C 8) alkyl. 14. The compound as described in the claim 13, wherein: Rla is one or more substituents independently selected from the group consisting of (C1-C8) alkyl, (C3-C10) cycloalkyl, (C1-C8) hydroxyalkyl, (C2-C8) hydroxyalkenyl, cyanoalkyl ( C1-C8), (C1-C8) alkoxy (C1-C8) alkyl, (C1-C8) monoalkyl (C1-C8) aminoalkyl, (C1-C8) azidoalkyl (C1-C8) alkylideido (C1-C8) alkyl, (phenyl or naphthyl) oxyalkyl (C 1 -C 8) carbonyloxyalkyl (C 1 -C 8), and (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group of nitrogen, oxygen and sulfur) alkyl ( C1-C8), - R2 is one or more substituents independently selected from the group consisting of hydrogen, chlorine or fluoro; R3 is phenyl substituted by one or more substituents independently selected from the group consisting of hydroxy, halo, (C1-C8) alkyl, (C1-C8) alkoxy, formyl, nitro, cyano, (C1-C8) aminoalkoxy, (C3) cycloalkyl -C10) aminoalkyl (C1-C8), hydroxyalkyl (C1-C8), ((C1-C8) monoalkylamino) (phenyl or naphthyl) (C1-C8) alkyl, (C1-C8) alkoxy (C1-C8) alkyl, amino, (C1-C8) monoalkyl amino, (C1-C8-) dialkylamino, mono (phenyl or naphthyl) (C 1 -C 8) alkyl, (C 1 -C 8) alkylcarbonylamino, (C 2 -C 8) alkenyl carbonylamino, (C 3 -CIO) carbonylamino (phenyl or naphthyl) carbonylamino (3-15 membered heterocyclyl) consisting of atoms carbon and from one to five heteroatoms selected from the group of nitrogen, oxygen and sulfur), carbonylamino, haloalkyl (C 1 -C 8) carbonylamino, alkoxy (C 1 -C 8) alkyl (C 1 -C 8) carbonylamino, alkoxy (C 1 -C 8) carbonylalkyl (C 1 -C 8) carbonylamino, (C 1 -C 8) alkyl sulfonylamino, amino (C 1 -C 8) alkyl, (C 1 -C 8) monoalkyl (C 1 -C 8) alkyl, (C 1 -C 8) dialkyl amino (C 1 -C 8) alkyl, mono ( phenyl or naphthyl) (C 1 -C 8) alkyl amino (C 1 -C 8) alkyl, (C 1 -C 8) alkylcarbonylammonium (C 1 -C 8) alkyl, (phenyl or naphthyl) carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) carbonyl ) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (C 1 -C 8) cycloalkylalkyl aminoal (C 1 -C 8) -alkyl, (C 1 -C 8) coxy (C 1 -C 8) carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8) alkylsulfonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) sulfonyl) (C 1 -C 8) alkyl) amino (C 1 -C 8) alkyl, (phenyl or naphthyl) sulfonylamino (C 1 -C 8) alkyl, ((phenyl or naphthyl) sulfonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, carboxy , (C 1 -C 8) alkoxycarbonyl, (C 1 -C 8) alkylcarbonyl, (hydroxy (C 1 -C 8) alkoxycarbonyl, aminocarbonyl, (C 1 -C 8) monoalkylaminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, (aminocarbonylalkyl (C 1 -C 8) C8)) aminocarbonyl, ((C 1 -C 8) aminoalkyl) aminocarbonyl, (C 1 -C 8) hydroxy (C 1 -C 8) alkylaminocarbonyl, hydroxyamidino, ureido, mono (C 1 -C 8) ureido, mono (phenyl or naphthyl) ureido, mono (phenyl or naphthyl) ) alkyl (Cl-C8) ureido, ((C1-C8) monoalkyl) (mono (phenyl or naphthyl)) ureido, (C1-C8 haloalkyl) carbonyl) ureido, ureido (C1-C8) alkyl, (C1-C8) monoalkyl ) ureidoalkyl (C1-C8), dialkyl (C1-C8) ureidoalkyl (C1-C8), mono (phenyl or naphthyl) ureidoalkyl (C1-C) 8), mono (phenyl or naphthyl) alkyl (C1-C8) ureidoalkyl (C1-C8), monohaloalkyl (C1-C8) ureidoalkyl (C1-C8), (haloalkyl (C1-C8)) (C1-C8 alkyl) ) ureido (C 1 -C 8) alkyl, (C 1 -C 8 alkoxy) carbonylalkyl (C 1 -C 8)) ureido (C 1 -C 8) alkyl, glycinamide, (C 1 -C 8) monoalkyl glycinamide, aminocarbonylglycinamide, (C 1 -C 8 alkoxy) alkyl ( C1-C8) carbonyl) glycinamide, (aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, (C 1 -C 8 alkoxy) carbonylalkyl (C 1 -C 8) carbonyl) (C 1 -C 8 alkyl) glycinamide, (C 1 -C 8 alkoxy) -C8) carbonylamino (C 1 -C 8) alkylcarbonyl) glycinamide, (phenyl or naphthyl) carbonylglycinamide, ((phenyl or naphthyl) carbonyl) (C 1 -C 8 alkyl) glycinamide, (mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, (mono (phenyl or naphthyl) aminocarbonyl) glycinamide, (mono "(phenyl or naphthyl) aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, alaninamide, heterocyclyl 3- 15 members consisting of carbon atoms and one to five heteroatoms selected from the group of nitrogen, oxygen and sulfur, and (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group - nitrogen, oxygen and sulfur) (C 1 -C 8) alkyl. 15. The compound as described in claim 14, wherein: Rla is one or more substituents independently selected from the group consisting of (C 1 -C 8) alkyl and (C 1 -C 8) hydroxyalkyl, - R 2 is one or more independently selected substituents from the group consisting of hydrogen, chlorine or fluoro; R3 is phenyl substituted by one or more substituents independently selected from the group consisting of halo, (C1-C8) alkyl, (C1-C8) alkoxy, formyl, nitro, (C3-C10) cycloalkyl (C1-C8) aminoalkyl, hydroxyalkyl (C1-C8), amino, alkyl (C1-C8) carbonylamino, haloalkyl (C1-C8) carbonylamino, alkoxy (C1-C8) (C1-C8) alkylcarbonylamino, (C1-C8) alkoxycarbonylalkyl (C1-C8) carbonylamino, (C1-C8) alkyl sulfonylamino, aminoalkyl (C1-C8), (C1-C8) monoalkylamino (C1-C8) alkyl, dialkyl (C1-C8) amino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) sulfonyl) (alkyl) (C1-C8)) (C1-C8) aminoalkyl, (C1-C8) alkylcarbonyl, aminocarbonyl, (C1-C8) monoalkylaminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, (aminocarbonylalkyl (C1-C8)) aminocarbonyl, ( (C 1 -C 8) aminoalkyl) aminocarbonyl, hydroxyamidino, ureido, (C 1 -C 8) haloalkyl carbonyl) ureido, ureido (C 1 -C 8) alkyl, glycinamide, monoalguyl (C1-C8) glycinamide, aminocarbonylglycinamide, (C1-C8) alkoxy (C1-C8) alkylcarbonyl) glycinamide, (aminocarbonyl) (C1-C8 alkyl) glycinamide, (C1-C8 alkoxy) carbonylaminoalkyl (C1- C8) carbonyl) glycinamide, alaninamide, and (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group of nitrogen, oxygen and sulfur) (C 1 -C 8) alkyl. 16. The compound as described in the claim 15, 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. 17. The compound as described in the claim 16, selected from the group consisting of the following compounds: (t rans) - l - ((4-c l o ro f eni l amino) methyl) carbonil-2, 5-dimethyl-4- (4-fluorobenzyl) piperazine; 1- ((4-chloro-2- (aminocarbonyl) phenylamino) methyl) carbonyl-2-methyl-4- (4-f luorobenzyl) piperazine; and 1 - ((4-c l o r or f e n i l a m i n o) methyl) carbonyl-2-methyl-4- (4-f luorobenzyl) iperazine. 18. The compound as described in claim 3, in which: R 4 is -C (R 8) 2-; Rs is methylene; Rs is -CÍO) -; and each R8 is independently selected from the group consisting of hydrogen, (C1-C8) alkyl, amino, monoalkyl (C1-C8) amino, dialkyl (C1-C8) amino, alkyl (C1-C8) carbonylamino, cycloalkyl (C3-C10) carbonylamino, cycloalkyl (C3-C10) alkyl (C1-C8) carbonylamino, alkoxy (C1-C8) ) carbonylamino, (C1-C8) alkyl sulfonylamino, (phenyl or naphthyl) carbonylamino, alkoxy (Cl-C8) carbonylalkyl (C 1 -C 8) carbonylamino, (C 1 -C 8) alkylcarbonylamino (C 1 -C 8) alkyl, (C 3 -CIO) carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8) alkoxycarbonylamino (C 1 -C 8) alkyl, (heterocyclyl) -15 members consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylaminoalkyl (C1-C8), (phenyl or naphthyl) sulfonylamino, (C1-C8) alkyl sulfonylaminoalkyl (C1 -C8), ureido, (C1-C8) monoalkyl ureido, monohaloalkyl (C1-C8) ureido, ureidoalkyl (C1-C8), (C1-C8) monoalkyl ureido (C1-C8) alkyl, (C1-C8) monohaloalkyl ureidoalkyl ( C1-C8), aminoalkyl (C 1 -C 8), (C 1 -C 8) monoalkyl amino (C 1 -C 8) alkyl, and (C 1 -C 8) dialkyl amino (C 1 -C 8) alkyl. 19. The compound as described in claim 18, wherein: R1 is one or more substituents independently selected from the group consisting of halo, (C1-C8) alkyl, (C3-C10) cycloalkyl, (C3-C10) cycloalkyl, aminoalkyl "(C1-C8), haloalkyl (C1-C8), hydroxyalkyl (C1-C8), hydroxyalkenyl (C2-C8), hydroxyalkynyl (C2-C8), (hydroxy) (phenyl or naphthyl) alkyl (C1-C8), cyano (C1-C8) alkyl, (C1-C8) haloalkylamino (C1-C8) alkyl, (C1-C8) alkoxy (C1-C8) alkyl, (phenyl or naphthyl) (C1-C8) alkoxy (C1-C8) alkyl , (C1-C8) alkylthio (C1-C8) alkyl, (C1-C8) hydroxyalkyl (C1-C8) alkyl, (C1-C8) aminoalkyl, (C1-C8) monoalkylamino (C1-C8) alkyl, dialkyl (C1) -C8) ammonioalkyl (C1-C8), mono (phenyl or naphthyl) aminoalkyl (C1-C8), mono (phenyl or naphthyl) alkyl (C1-C8) aminoalkyl (C1-C8), azidoalkyl (C1-C8) monoalkyl ( C1-C8) ureidoalkyl (C1-C8), (C1-C8 alkoxy) carbonylalkyl (C1-C8)) ureidoalkyl (C1-C8), hydroxyalkyl (C1-C8) aminoal (C 1 -C 8), (phenyl or naphthyl) oxyalkyl (C 1 -C 8) carbonyloxyalkyl (C 1 -C 8), (phenyl or naphthyl) alkoxy (C 1 -C 8) alkyl (C 1 -C 8) carbonyloxyalkyl (C 1 -C 8), alkyl (C1-C8) carbonylalkyl (C1-C8), (C1-C8) alkoxycarbonyl, (C1-C8) alkoxycarbonylalkyl (C1-C8), and (3-15 membered heterocyclyl consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) alkyl (C1-C8); R2 is one or more substituents independently selected from the group consisting of hydrogen and halo; R3 is phenyl optionally substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, (C1-C8) alkyl, (C1-C8) alkoxy, hydroxy (C1-C8) alkoxy, halo (C1-C8) alkyl , formyl, nitro, cyano, (C1-C8) aminoalkoxy, (C3-C10) cycloalkyl, (C3-C10) cycloalkyl (C1-C8) aminoalkyl, (phenyl or naphthyl) (C1-C8) alkyl, hydroxyalkyl (C1- C8), ((C 1 -C 8) monoalkyl) amino (phenyl or naphthyl) alkyl (C 1 -C 8), alkoxy (C 1 -C 8) alkyl (C 1 -C 8), amino, (C 1 -C 8) aminoalkyl, dialkyl (C 1 -C 8) amino, mono (phenyl or naphthyl) alkyl (C 1 -C 8) amino, alkyl (C1-C8) carbonylamino, (C2-C8) alkenyl carbonylamino, cycloalkyl (C3-C10) carbonylamino, (phenyl or naphthyl) carbonylamino, (3-15 membered heterocyclyl consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylamino, haloalkyl (C 1 -C 8) carbonylamino, (C 1 -C 8) alkoxy (C 1 -C 8) alkyl carbonylamino, (C 1 -C 8) alkoxy carbonylalkyl (C 1 -C 8) carbonylamino, (C 1 -C 8 alkyl) carbonyl) (C 1 -C 8 alkyl) )) amino, alkyl (C1-C8) sulfonylamino, (C1-C8) aminoalkyl, (C1-C8) monoalkylamino (C1-C8) alkyl, (C1-C8) dialkylamino (C1-C8) alkyl, mono (phenyl or naphthyl) amino (C 1 -C 8) alkyl, mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminoalkyl (C 1 -C 8), alkyl (C 1 -C 8) carbonylamino (C 1 -C 8) alkyl, (phenyl or naphthyl) carbonylaminoalkyl (C1-C8), (C1-C8 alkyl) carbonyl) (alkyl) (C 1 -C 8)) (C 1 -C 8) aminoalkyl, (C 1 -C 8) alkyl (C 1 -C 8) alkylamino (C 1 -C 8) alkyl, (C 1 -C 8) alkoxy carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8) alkoxycarbonylalkyl ( C1-C8) carbonylaminoalkyl (C1-C8), (C1-C8alkoxy) carbonyl) (C1-C8alkyl)) aminoalkyl (C1-C8), alkyl (C1-C8) sulfonylaminoalkyl (C1-C8), (alkyl) (C 1 -C 8) sulfonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (phenyl or naphthyl) sulfonylamino (C 1 -C 8) alkyl, ((phenyl or naphthyl) sulfonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) aminoalkyl (C 1 -) C8), carboxy, to the coxi (Cl - C 8) carboni 1 or, alkyl (Cl - C 8) carbonyl or, (hydroxy (C1-C8) alkoxy) carbonyl, aminocarbonyl, (C1-C8) monoalkylaminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, (aminocarbonylalkyl (C1-C8)) aminocarbonyl, (aminoalkyl) (C 1 -C 8)) aminocarbonyl, (hydroxy (C 1 -C 8) alkyl) aminocarbonyl, dialkyl (C 1 -C 8) aminocarbonylalkyl (C 1 -C 8), hydroxyamidino, ureido, mono (C 1 -C 8) alkyl ureido, mono (phenyl or naphthyl) ureido , mono (phenyl or naphthyl) alkyl (C 1 -C 8) ureido, (mono (C 1 -C 8) alkyl) (mono (phenyl or naphthyl)) ureido, (haloalkyl) (C1-C8) carbonyl) ureido, ureidoalkyl (C1-C8), monoalkyl (C1-C8) ureidoalkyl (C1-C8), dialkyl (C1-C8) ureidoalkyl (C1-C8), mono (phenyl or naphthyl) ureidoalkyl (C1-C8), mono (phenyl or naphthyl) alkyl (C1-C8) ureidoalkyl (C1-C8), monohaloalkyl (C1-C8) ureidoalkyl (C1-C8), (haloalkyl (C1-C8)) (alkyl) (C1-C8)) ureidoalkyl (C1-C8), (C1-C8 alkoxy) carbonylalkyl (C1-C8)) ureidoalkyl (C1-C8), glycinamide, monoalkyl (C1-C8) glycinamide, aminocarbonylglycinamido, (C1-C8 alkoxy) (C1-C8) alkylcarbonyl) glycinamide, (aminocarbonyl) (C1-C8 alkyl) glycinamide, (C1-C8 alkoxy) carbonylalkyl (C1- C8) carbonyl) (C 1 -C 8 alkyl) glycinamide, (C 1 -C 8 alkoxy) carbonylamino (C 1 -C 8) alkylcarbonyl) glycinamide, (phenyl or naphthyl) carbonylglycinamide, ((phenyl or naphthyl) carbonyl) (alkyl (C 1)) -C8)) glycinamide, (mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonyl) glycinamide, (mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, (mono (phenyl or naphthyl) aminocarbonyl) glycinamide, (mono (phenyl or naphthyl) aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, alaninamide, 3-15 merazole heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxy geno and sulfur) (C1-C8) alkyl. 20. The compound as described in claim 19, wherein: Rla is one or more substituents independently selected from the group consisting of (C 1 -C 8) alkyl, '(C3-C10) cycloalkyl, (C1-C8) hydroxyalkyl, hydroxyalkenyl (C2-C8), cyano (C1-C8) alkyl, (C 1 -C 8) alkoxy (C 1 -C 8) alkyl, (C 1 -C 8) monoalkyl amino (C 1 -C 8) alkyl, (C 1 -C 8) azido (C 1 -C 8) alkyl (C 1 -C 8) ureido (C 1 -C 8) alkyl, (phenyl or naphthyl) ) (C 1 -C 8) oxyalkylcarbonyloxyalkyl (C 1 -C 8), and (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) alkyl (C 1 -) C8), - R2 is one or more substituents independently selected from the group consisting of hydrogen, chlorine or fluoro; R3 is phenyl substituted by one or more substituents independently selected from the group consisting of hydroxy, halo, (C1-C8) alkyl, (C1-C8) alkoxy, formyl, nitro, cyano, (C1-C8) aminoalkoxy, (C3) cycloalkyl -C10) aminoalkyl (C1-C8), hydroxyalkyl (C1-C8), ((C1-C8) monoalkylamino) (phenyl or naphthyl) (C1-C8) alkyl, (C1-C8) alkoxy (C1-C8) alkyl, amino, (C1-C8) aminoalkyl, (C1-C8) dialkylamino, mono (phenyl or naphthyl) (C1-C8) alkyl amino, (C1-C8) alkyl carbonylamino, (C2-C8) alkenyl carbonylamino, cycloalkyl (C3 -C10) barbonylamino, (phenyl or naphthyl) carbonylamino, (3-15 membered heterocyclyl consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylamino, (C1-C8) haloalkyl carbonylamino, (C1-C8) alkoxy alkyl (C1 -C8) carbonylamino, (C1-C8) alkoxycarbonylalkyl (C1-C8) carbonylamino, alkyl (C1-C8) sulfonylamino, (C1-C8) aminoalkyl, (C1-C8) monoalkylamino (C1-C8) alkyl, (C1-C8) dialkylamino (C1-C8) alkyl, mono (phenyl or naphthyl) C 1 -C 8 alkyl amino (C 1 -C 8) alkyl, (C 1 -C 8) alkyl carbonylamino (C 1 -C 8) alkyl, (phenyl or naphthyl) carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) carbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (C 1 -C 8) alkyl (C 1 -C 8) alkylamino (C 1 -C 8) alkyl, (C 1 -C 8) alkoxy (C 1 -C 8) carbonylamino (C 1 -C 8) alkylamino ), (C 1 -C 8) alkyl sulfonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) sulfonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (phenyl or naphthyl) sulfonylamino (C 1 -C 8) alkyl , ((phenyl or naphthyl) sulfonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, carboxy, (C 1 -C 8) alkoxycarbonyl, (C 1 -C 8) alkylcarbonyl, (hydroxy (C 1 -C 8) alkoxy) carbonyl, aminocarbonyl, (C 1 -C 8) monoalkyl aminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, (aminocarbonylalkyl (C 1 -C 8) aminocarbonyl, (amino (C 1 -C 8) amino) alkylcarbonyl, (hydroxy (C 1 -C 8) alkyl) aminocarbonyl, hydroxyamidino, ureido, mono (C1-C8) ureido, mono (phenyl or naphthyl) ureido, mono (phenyl or naphthyl) alkyl (C1-C8) urei (mono- (phenyl or naphthyl)) ureido, (C1-C8-haloalkyl) carbonyl) ureido, ureido (C1-C8) alkyl, (C1-C8) -alkyl ureidoalkyl (C1-C8) alkyl , (C 1 -C 8) dialkyl ureido (C 1 -C 8) alkyl, mono (phenyl or naphthyl) ureidoalkyl (C 1 -C 8), mono (phenyl or naphthyl) alkyl (C 1 -C 8) ureido (C 1 -C 8) alkyl, monohaloalkyl (C 1 -C 8) -C8) ureidoalkyl (C1-C8), (haloalkyl (C1-C8)) (alkyl (C1-C8)) ureidoalkyl (C1-C8), (C1-C8 alkoxy) carbonylalkyl (C1-C8)) ureidoalkyl (C1 -C8), glycinamide, (C1-C8) monoalkyl glycinamide, aminocarbonylglycinamido, (C1-C8alkoxy) (C1-C8) alkylcarbonyl) glycinamide, (aminocarbonyl) (C1-C8alkyl) glycinamide, (C1-C8alkoxy) -C8) carbonylalkyl (C 1 -C 8) carbonyl) (C 1 -C 8 alkyl) glycinamide, (C 1 -C 8 alkoxy) carbonylamino (C 1 -C 8) alkylcarbonyl) glycinamide, (phenyl or naph il) carbonylglycinamide, ((phenyl or naphthyl) ) carbonyl) (C 1 -C 8 alkyl) glycinamide, (mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, (mono (phenyl) or naphthyl) aminocarbonyl) glycinamide, (mono (phenyl or naphthyl) aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, alaninamide, 3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of it consists of nitrogen, oxygen and sulfur and (3-15 membered heterocyclyl consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (C 1 -C 8) alkyl. 21. The compound as described in the claim 20, wherein: Rla is one or more substituents independently selected from the group consisting of (C 1 -C 8) alkyl and (C 1 -C 8) hydroxyalkyl, - R 2 is one or more substituents independently selected from the group consisting of hydrogen, chloro or fluoro; R3 is phenyl substituted by one or more substituents independently selected from the group consisting of halo, (C1-C8) alkyl, (C1-C8) alkoxy, formyl, nitro, (C3-CIO) cycloalkyl (C1-C8) aminoalkyl, hydroxyalkyl (C1-C8), amino, alkyl (C 1 -C 8) carbonylamino, haloalkyl (C 1 -C 8) carbonylamino, alkoxy (C 1 -C 8) alkyl (C 1 -C 8) carbonylamino, alkoxy (C 1 -C 8) carbonyl (C 1 -C 8) alkyl carbonylamino, (C 1 -C 8) alkyl sulfonylamino, (C 1 -C 8) aminoalkyl, (C 1 -C 8) monoalkyl amino (C 1 -C 8) alkyl, (C 1 -C 8) dialkyl (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) sulfonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (C 1 -C 8) alkylcarbonyl, aminocarbonyl, (C 1 -C 8) monoalkylaminocarbonium, mono (phenyl or naphthyl) aminocarbonyl, (aminocarbonylalkyl (C 1 -C 8) alkyl) aminocarbonyl , ((C 1 -C 8) aminoalkyl) aminocarbonyl, hydroxyamidino, ureido, (C 1 -C 8) haloalkyl carbonyl) ureido, ureido (C 1 -C 8) alkyl, glycinamide, monoalkyl (C1-C8) glycinamide, aminocarbonylglycinamide, (C1-C8) alkoxy (C1-C8) alkylcarbonyl) glycinamide, (aminocarbonyl) (C1-C8 alkyl) glycinamide, (C1-C8 alkoxy) carbonylaminoalkyl (C1-C8) carbonyl) glycinamide, alaninamide, and (heterocyclyl 3-15 members consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (C 1 -C 8) alkyl. 22. The compound as described in claim 21, 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 one of R8 is hydrogen and the other R8 is selected from the group consisting of amino, (C1-C8) alkylcarbonylamino, cycloalkyl (C3-C0) carbonylamino, cycloalkyl (C3-C10) alkyl (C1-C8) carbonylamino, alkoxy (C 1 -C 8) carbonylamino, (C 1 -C 8) alkyl sulfonylamino, (phenyl or naphthyl) carbonylamino, (C 1 -C 8) alkoxy carbonylalkyl (C 1 -C 8) carbonylamino, alkyl (C 1 -C 8) carbonylamino (C 1 -C 8) alkyl, cycloalkyl (C3-C10) carbonylaminoalkyl (C1-C8), (C1-C8) alkoxycarbonylamino (C1-C8) alkyl, (3-15 membered heterocyclyl which consists of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylaminoalkyl (C1-C8), (phenyl or naphthyl) sulfonylamino, alkyl (C1-C8) sulfonylamino (C1-C8), ureido, monoalkyl (C1-C8) ureido, monohaloalkyl (C1-C8) ureido , (C 1 -C 8) ureidoalkyl, (C 1 -C 8) monoalkyl ureido (C 1 -C 8) alkyl, (C 1 -C 8) monohaloalkyl ureido (C 1 -C 8) alkyl, and (C 1 -C 8) aminoalkyl. 23. The compound as described in claim 22, 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- (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) ropil) carbonyl -2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -3- (amino) ropil) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -3- (t-butoxycarbonylamino) propyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) iperazine; (trans) -1- (2- (4-chlorophenyl) -2- ((ethoxycarbonylmethylcarbonylamino) -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) carbonylamino) ethyl) -carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -2- ((4-methoxy-enylmethyl) -carbonylamino) -ethyl) -carbonyl-2,5-dimethyl-4- (4-f-luorobenzyl) -piperazine; (trans) -1- (2- (4-chlorofenyl) -2- ((2,4-dinitrofenyl) sulfonylamino) -ethyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- (2- (4-chlorofenyl) -2- (cyclopropylcarbonylamino) ethyl) -carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- (2- (4-chlorophenyl) -2- ((2-cyclopropylethyl) carbonylamino) -ethyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- (2- (4-chloro-enyl) -3- ((2-methylpropyl) carbonylamino) -propyl) carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (trans) -1- (2- (4-chlorofenyl) -3- (cyclopentylcarbonylamino) propyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; (t r a n s) - 1 - (2 - (4-c l o r o f e n i l) - 3 - (N 1 - (t-butyl) ureido) propyl) carbonyl-2,5-dimethyl-4 - (4-f luorobenzyl) piperazine; (trans) -1- (2- (4-chloro-enyl) -3- (N '- (ethyl) ureido) propyl) carbonyl-2, 5-dimethyl-4- (4-f luorobenzyl) piperazine, - (trans ) -1- (2- (4-chlorofenyl) -3- (N 1 - (3-chloropropyl) ureido) propyl) -carbonyl-2,5-dimethyl-4- (4-f luorobenzyl) piperazine; and (trans) -1- (2- (4-chlorofenyl) -3- ((morpholin-4-yl) carbonylamino) -propyl) carbonyl -2,5-dimethyl-4 (4-f luorobenzyl) piperazine . 24. The compound as described in claim 1, wherein: R3 is a heterocyclic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, (C1-C8) alkyl, (C1-C8) alkylsulfonyl, (phenyl or naphthyl) sulfonyl, alkoxy ( C1-C8), hydroxyalkoxy (C1-C8), haloalkyl (C1-C8), formyl, nitro, cyano, haloalkoxy (C1-C8), alkenyl (C2-C8), alkynyl (C2-C8), phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, amino, (C1-C8) aminoalkyl, dialkyl (C1-C8) amino, mono (phenyl or naphthyl) amino, mono (phenyl or naphthyl) alkyl (C 1 -C 8) amino, alkyl (C 1 -C 8) carbonylamino, alkoxy (C 1 -C 8) carbonylamino, alkenyl (C 2 -C 8) carbonylamino, cycloalkyl (C 3 -CIO ) carbonylamino, (phenyl or naphthyl) carbonylamino, haloalkyl (C 1 -C 8) carbonylamino, alkoxy (C 1 -C 8) alkyl (C 1 -C 8) carbonylamino, alkoxy (C 1 -C 8) carbonylalkyl (C 1 -C 8) carbonylamino, (C 1 -C 8 alkyl) -C8) carbonyl) (C 1 -C 8 alkyl) amino, (C 1 -C 8 alkoxycarbonyl) (C 1 -C 8 alkyl) amino, (C 1 -C 8) alkyl sulfonylamino, (C 1 -C 8) aminoalkyl, monoalkyl (C1-C8) (C1-C8) aminoalkyl, (C1-C8) dialkylamino (C1-C8) alkyl, (C1-C8) alkylcarbonylamino (C1-C8) alkyl, (phenyl or naphthyl) carbonylamino (C1-C8) alkyl, (C 1 -C 8 alkylcarbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (C 1 -C 8) alkoxycarbonylamino (C 1 -C 8) alkyl, carboxy, (C 1 -C 8) alkoxycarbonyl, (phenyl or naphthyl) (C 1 -C 8) alkoxycarbonyl, (C 1 -C 8) alkylcarbonyl, (phenyl or naphthyl) carbonyl, (phenyl or naphthyl) alkyl (C 1 -C 8) carbonyl, aminocarbonyl, mo (C 1 -C 8) aminocarbonyl, (C 1 -C 8) dialkyl aminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, aminocarbonylalkyl (C 1 -C 8), (C 1 -C 8) monoalkylaminocarbonylalkyl (C 1 -C 8), (C 1 -C 8) dialkyl aminocarbonylalkyl (C1-C8), mono (phenyl or naphthyl) aminocarbonylalkyl (C1-C8), guanidino, ureido, monoalkyl (Cl-C8) ureido, ureidoalkyl (C1-C8), monoalkyl (C1-C8) ureidoalkyl (C1-C8), and glycinamide. 25. The compound as described in claim 24, wherein: R4 is -0-, -N (R7) - or -C (R8) -; Rs is an alkylene chain; R7 is selected from the group consisting of hydrogen, (C1-C8) alkyl, phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, (C1-C8) alkyl carbonyl, (C1-C8) alkyl carbonylalkyl (C1 -C8), (phenyl or naphthyl) alkyl (C1-C8) carbonyl, (phenyl or naphthyl) alkyl (C1-C8) carbonylalkyl (C 1 -C 8), aminocarbonyl, (C 1 -C 8) monoalkylaminocarbonyl, dialkyl (C 1 -C 8) aminocarbonyl, and (C 1 -C 8) alkoxycarbonyl; and each R8 is independently selected from the group consisting of hydrogen, (C1-C8) alkyl, phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, hydroxy, (C1-C8) alkoxy, hydroxy (C1-C8) alkyl, (C1-C8) alkoxy (C1-C8) alkyl, amino, (C1-C8) aminoalkyl) amino , dialkyl (C1-C8) amino, alkyl (C 1 -C 8) carbonylamino, cycloalkyl (C 3 -CIO) carbonylamino, cycloalkyl (C 3 -C 10) alkyl (C 1 -C 8) carbonylamino, alkoxy (C 1 -C 8) carbonylamino, alkyl (C 1 -C 8) sulfonylamino, (phenyl or naphthyl) carbonylamino, (C 1 -C 8) alkoxycarbonylalkyl (C 1 -C 8) carbonylamino, (C 1 -C 8 alkylcarbonyl) (C 1 -C 8 alkyl) amino, (phenyl or naphthyl) alkyl (C 1 -C 8) carbonylamino, (( phenyl or naphthyl) (C 1 -C 8) alkylcarbonyl) (C 1 -C 8 alkyl) amino, (C 1 -C 8) alkylcarbonylamino (C 1 -C 8) alkyl, cycloalkyl. (C3-C10) carbonylaminoalkyl (C1-C8), alkoxy (C1-C8) carbonylaminoalkyl (C1-C8), (C1-C8alkyl) carbonyl) (C1-C8alkyl) aminoalkyl (C1-C8), ( phenyl or naphthyl) (C 1 -C 8) alkylcarbonylamino (C 1 -C 8) alkyl, (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur), carbonylaminoalkyl (C 1 -C 8), ((phenyl or naphthyl) (C 1 -C 8) alkylcarbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (phenyl or naphthyl) sulfonylamino, (C 1 -C 8) alkyl sulfonylaminoalkyl ( C1-C8), ureido, (C1-C8) monoalkyl ureido, monohaloalkyl (C1-C8) ureido, dialkyl (C1-C8) ureido, ureidoalkyl (C1-C8), monoalkyl (C1-C8) ureidoalkyl (C1-C8) , (C1-C8) dialkyldido (C1-C8) alkyl, (C1-C8) monohaloalkyl ureido (C1-C8) alkyl, (C1-C8) aminoalkyl, (C1-C8) monoalkylamino (C1-C8) alkyl, dialkyl (C1) -C8) aminoalkyl (C1-C8), carboxyalkyl (C1-C8), alkoxy (C1-C8) carbonylalkyl (C1-C8), amin acarbonylalkyl (C1-C8), (C1-C8) monoalkylaminocarbonylalkyl (C1-C8), and dialkyl (C1-C8) aminocarbonylalkyl (C1-C8). 26. The compound as described in the claim 25, wherein: R4 is -0-; R5 is methylene; and Rs is -CÍO) -. 27. The compound as described in the claim 26, wherein: Rla is one or more substituents independently selected from the group consisting of halo, (C1-C8) alkyl, (C3-C10) cycloalkyl, (C3-C10) cycloalkyl (C1-C8) aminoalkyl, haloalkyl ( C1-C8), hydroxyalkyl (C1-C8), hydroxyalkenyl (C2-C8), hydroxyalkynyl (C2-C8), (hydroxy) (phenyl or naphthyl) alkyl (C1-C8), cyano (C1-C8) alkyl, haloalkyl (C1-C8) carbonylamino (C1-C8) alkyl, alkoxy ( C1-C8) (C1-C8) alkyl, (phenyl or naphthyl) (C1-C8) alkoxy (C1-C8) alkyl, (C1-C8) alkyl (C1-C8) alkyl, (C1-C8) hydroxyalkyl thioalkyl ( C1-C8), (C1-C8) aminoalkyl, (C1-C8) monoalkylamino (C1-C8) alkyl, (C1-C8) dialkylamino (C1-C8) alkyl, mono (phenyl or naphthyl) aminoalkyl (C1-C8) , mono (phenyl or naphthyl) alkyl (C1-C8) aminoalkyl (C1-C8), azidoalkyl (C1-C8) monoalkyl (C1-C8) ureidoalkyl (C1-C8), (C1-C8 alkoxy) carbonylalkyl (C1- C8)) ureidoalkyl (C1-C8), hydroxyalkyl (C1-C8) aminoalkyl (C1-C8), (phenyl or naphthyl) oxyalkyl (C1-C8) carbonyloxyalkyl (C1-C8), (phenyl or naphthyl) alkoxy (C1- C8) C8) C 1 -C 8 alkylcarbonyloxyalkyl (C 1 -C 8) alkyl, (C 1 -C 8) alkylcarbonylalkyl (C 1 -C 8), (C 1 -C 8) alkoxycarbonyl, (C 1 -C 8) alkoxycarbonylalkyl (C 1 -C 8), and (3-15 member heterocyclyl consisting of ato carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (C 1 -C 8) alkyl; and R2 is one or more substituents independently selected from the group consisting of hydrogen and halo. 28. The compound as described in claim 27, wherein R3 is 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, indolyl, 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, thiazole idinyl, thiadiazolyl, triazolyl, tetrazolyl, tetrahydrofuryl, tetrahydropyranyl, thienyl, thiamorpholinyl, thiamorpholinyl sulfoxide, and thiamorpholinyl sulfone. 29. The compound as described in the claim 28, wherein R3 is benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, quinolinyl, indolyl, indolinyl, oxazolyl, imidazolyl, or benzothienyl. 30. The compound as described in the claim 29, specifically (trans) -1- ((benzo [b] pyran-2-on-7-yloxy) methyl) carbonyl-2,5-dimethyl-4- (4-fluorobenzyl) piperazine. 31. A pharmaceutical composition useful in the treatment of an inflammatory disorder in a human in need of such treatment, which composition comprises a therapeutically effective amount of a compound as described in claim 1. 32. The use of a compound as described in claim 1, for the preparation of a medicament for the treatment of an inflammatory disorder in a human, wherein the treatment comprises administering to a human in need of such treatment a therapeutically effective amount of such a compound 33. A pharmaceutical composition useful for treating an inflammatory disorder in a human in need of such treatment, which composition comprises a therapeutically effective amount of a compound of formula (Ib): "wherein: R 2 is one or more substituents independently 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, alkyl (C 1 -C 8) sulfinyl, (C 1 -C 8) alkylsulfonyl, C 1 -C 8 alkylthio (C 1 -C 8) alkyl, (C 1 -C 8) alkyl sulfinylalkyl (C 1 -C 8), (C 1 -C 8) alkyl sulfonylalkyl (C 1) -C8), (C1-C8) alkoxy, (phenyl or naphthyl) oxy, halo (C1-C8) alkyl, formyl, formylalkyl (C1-C8), nitro, nitroso, cyano, (phenyl or naphthyl) alkoxy (C1-C8) ), haloalkoxy (C1-C8), cycloalkyl (C3-C10), cycloalkyl (C3-C10) alkyl (C1-C8), (hydroxy) cycloalkyl (C3-C10) alkyl (C1-C8), (C3-C10) cycloalkyl amino, (C3-C10) cycloalkyl (C1-C8) aminoalkyl, (C3-C10 cycloalkyl) (C1-C8) alkyl) amino, (C1-C8 cycloalkylalkyl) ) amino (C1-C8) alkyl, cyano (C1-C8) alkyl, (C2-C8) alkenyl, (C2-C8) alkynyl, phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, (phenyl or naphthyl) alkenyl (C2-C8), hydroxyalkyl (C1-C8), (hydroxy) (phenyl or naphthyl) (C1-C8) alkyl, (C1-C8) hydroxyalkyl thioalkyl (C1-C8), (C2-C8) hydroxyalkenyl, (C2-C8) hydroxyalkynyl, (C1-C8) alkoxy (C1-C8) alkyl, (C1-C8) alkoxy (phenyl or naphthyl) alkyl (C1- C8), (phenyl or naphthyl) oxyalkyl (C1-C8), (phenyl or naphthyl) alkoxy (C1-C8) alkyl (C1-C8), amino, (C1-C8) aminoalkyl, dialkyl (C1-C8) amino , mono (phenyl or naphthyl) amino, mono (phenyl or naphthyl) (C1-C8) alkyl amino, (C1-C8) aminoalkyl, (C1-C8) monoalkyl amino (C1-C8) alkyl, (C1-C8) dialkylamino (C1-C8) alkyl, hydroxyalkyl (C1- C8) (C1-C8) aminoalkyl, mono (phenyl or naphthyl) aminoalkyl (C1-C8), mono (phenyl or naphthyl) alkyl (C1-C8) aminoalkyl (C1-C8), alkyl (C1-C8) carbonylamino, (C 1 -C 8 alkylcarbonyl) (C 1 -C 8 alkyl) amino, (C 1 -C 8) alkyl carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) carbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (C 1 -C 8) alkoxy carbonylamino, (C 1 -C 8 alkoxy) carbonyl (alkyl) (C1-C8)) amino, (C1-C8) alkoxycarbonylaminoalkyl (C1-C8), (C 1 -C 8 alkoxycarbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, carboxy, (C 1 -C 8) alkoxycarbonyl, (phenyl or naphthyl) (C 1 -C 8) alkoxycarbonyl, alkyl (C 1 -C 8) -C8) carbonyl, alkyl (C1-C8) carbonylalkyl (C1-C8), (phenyl or naphthyl) carbonyl, (phenyl or naphthyl) carbonylalkyl (C1-C8), (phenyl or naphthyl) alkyl (C 1 -C 8) carbonyl, (phenyl or naphthyl) alkyl (C 1 -C 8) carbonylalkyl (C 1 -C 8), carboxyalkyl (C 1 -C 8), alkoxy (C 1 -C 8) carbonylalkyl (C1-C8), (phenyl or naphthyl) (C1-C8) alkoxycarbonylalkyl (C1-C8), alkoxy (C1-C8) alkyl (C1-C8) carbonyloxyalkyl (C1-C8), aminocarbonyl, monoalkyl (C1-C8) aminocarbonyl, dialkyl (C 1 -C 8) aminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonyl, aminocarbonylalkyl (C 1 -C 8), mono (C 1 -C 8) alkyl aminocarbonylalkyl (C 1 -C 8), dialkyl (C 1 -C 8) aminocarbonylalkyl (C 1 -C 8), mono (phenyl or naphthyl) aminocarbonylalkyl (C 1 -C 8), mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonylalkyl (C 1 -C 8), amidino, guanidino, ureido, mono (C1-C8) ureido, dialkyl (C1-C8) ureido, ureidoalkyl (C1-C8), (C1-C8) monoalkyl ureidoalkyl (C1-C8), dialkyl (C1-C8) ureidoalkyl (C1-C8), heterocyclyl of 3-15 members consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and (3-15 membered heterocyclyl which consists of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (C 1 -C 8) alkyl, - R 3 is a carbocyclic ring system substituted by one or more substituents independently selected from the group consisting of 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) alkylsulphinyl, (C 1 -C 8) alkyl, phenytoin, (phenyl) or naphthyl) sulfonyl, alkyl (C1-C8) thioalkyl (C1-C8), alkyl (C1-C8) sulfinylalkyl (C1-C8), (C 1 -C 8) alkyl sulfonylalkyl (C 1 -C 8), alkoxy (C 1 -C 8), hydroxyalkoxy (C 1 -C 8), (phenyl or naphthyl) oxy, haloalkyl (C 1 -C 8), formyl, formylalkyl (C 1 -C 8) , nitro, nitroso, cyano, (phenyl or naphthyl) alkoxy (C1-C8), haloalkoxy (C1-C8), aminoalkoxy (C1-C8), cycloalkyl (C3-C10), cycloalkyl (C3-C10) alkyl (C1- C8), (hydroxy) (C3-C10) cycloalkyl (C1-C8) alkyl, (C3-C10) cycloalkyl amino, (C3-C10) cycloalkyl (C1-C8) aminoalkyl, (C1-C8) cyanoalkyl, alkenyl (C2) -C8), (C2-C8) alkynyl, phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, (phenyl or naphthyl) alkenyl (C2-C8), hydroxyalkyl (C1-C8), (hydroxy) ( phenyl or naphthyl) (C 1 -C 8) alkyl, ((C 1 -C 8) amino) alkyl (phenyl or naphthyl) alkyl (C 1 -C 8), (hydroxy (C 1 -C 8) alkyl) thio (C 1 -C 8) alkyl, hydroxyalkenyl (C 2) -C8), hydroxyalkynyl (C2-C8), (C1-C8) alkoxy (C1-C8) alkyl, (C1-C8) alkoxy (phenyl or naphthyl) (C1-C8) alkyl, (phenyl or naphthyl) oxyalkyl (C1-C8), (phenyl or naphthyl) (C1-C8) alkoxy (C1-C8) alkyl , amino, (C1-C8) aminoalkyl, (C1-C8) dialkylamino, mono (phenyl or naphthyl) amino, mono (phenyl or naphthyl) alkyl (C1-C8) amino, amino (C1-C8) aminoalkyl), ( 3-15 membered heterocyclyl consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) amino, (C3-C10) cycloalkyl (C1-C8) alkyl) amino, alkyl ( C1-C8) carbonylamino, (C1-C8) alkoxy alkylcarbonylamino, (C2-C8) alkenyl carbonylamino, cycloalkyl (C3-C0) carbonylamino, (phenyl or naphthyl) carbonylamino, (3-15 membered heterocyclyl consisting of carbon atoms and from one to five _ heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylamino, haloalguil (C 1 -C 8) carbonylamino, (C 1 -C 8) alkoxy (C 1 -C 8) alkyl carbonylamino, (C 1 -C 8) alkoxy carbonylalkyl (C 1 -C 8) carbonylamino, (C 1 -C 8 alkyl) carbonyl) (C 1 -C 8 alkyl) )) amino, (C1-C8 alkoxy) carbonyl) (C 1 -C 8 alkyl) amino, (C 1 -C 8) alkyl sulfonylamino, aminoalkyl (C1-C8), (C1-C8) monoalkylamino (C1-C8) alkyl, dialkyl (C1-C8) aminoalkyl (C1-C8), hydroxyalkyl (C1-C8) aminoalkyl (C 1 -C 8), mono (phenyl or naphthyl) aminoalkyl (C 1 -C 8), mono (phenyl or naphthyl) alkyl (C 1 -C 8) ammonium (C 1 -C 8) alkyl, alkyl (C 1 -C 8) carbonylamino (C 1 -C 8) alkyl, (phenyl or naphthyl) carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) carbonyl) (alkyl) (C1-C8)) (C1-C8) aminoalkyl, (C1-C8) cycloalkylalkyl) amino (C1-C8) alkyl, (C1-C8) alkoxycarbonylamino (C1-C8) alkyl, (C1-C8) alkoxycarbonylalkyl (C1 -C8) carbonylaminoalkyl (C1-C8), (C 1 -C 8 alkoxycarbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (C 1 -C 8) alkyl sulfonylamino (C 1 -C 8) alkyl, (alkyl) (C 1 -C 8) sulfonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (phenyl or naphthyl) sulfonylamino (C 1 -C 8) alkyl, ((phenyl or naphthyl) sulfonyl) (C 1 -C 8 alkyl)) (C 1 -C 8) aminoalkyl (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) amino (C 1 -C 8) alkyl, carboxy, alkoxy (C 1 -C 8) -C8) carbonyl, (phenyl or naphthyl) (C1-C8) alkoxycarbonyl, (C1-C8) alkylcarbonyl, (phenyl or naphthyl) carbonyl, (phenyl or naphthyl) alkyl (C1-C8) carbonyl, (hydroxyalkoxy (C1 -C8)) carbonyl, carboxyalkyl (C1-C8), alkoxy (C1-C8) carbonylalkyl (C1-C8), (phenyl or naphthyl) alkoxy (C1-C8) carbonylalkyl (C1-C8), alkoxy (C1-C8) (C 1 -C 8) alkylcarbonyloxyalkyl (C 1 -C 8), dialkyl (C 1 -C 8) arainocarbonyloxyalkyl (C 1 -C 8), alkyl (C 1 -C 8) carbonylalkyl (C 1 -C 8), (phenyl or naphthyl) carbonylalkyl (C 1 -C 8) , (phenyl or naphthyl) C 1 -C 8 alkylcarbonylalkyl (C 1 -C 8), aminocarbonyl, (C 1 -C 8) monoalkyl aminocarbonate nyl, dialkyl (C1-C8) aminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, mono (phenyl or naphthyl) alkyl (C1-C8) aminocarbonyl, (aminocarbonylalkyl (C1-C8)) aminocarbonyl, ((C1-C8) alkyl) aminocarbonylalkyl (C 1 -C 8)) aminocarbonyl, (C 1 -C 8) alkylaminocarbonyl, (C 1 -C 8) alkoxycarbonylalkyl (C 1 -C 8) alkyl aminocarbonyl, (C 1 -C 8) aminocarbonyl aminocarbonyl, (C 1 -C 8 hydroxyalkyl) )) aminocarbonyl, aminocarbonylalkyl (C 1 -C 8), (C 1 -C 8) monoalkyl aminocarbonylalkyl (C 1 -C 8), dialkyl (C 1 -C 8) aminocarbonylalkyl (C 1 -C 8), mono (phenyl- or naphthyl) aminocarbonylalkyl (C 1 -C 8) , mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonylalkyl (C 1 -C 8), amidino, hydroxyamidino, guanidino, ureido, mono (C 1 -C 8) alkylidene, mono (phenyl or naphthyl) ureido, mono (phenyl or naphthyl) (C 1 -C 8) alkyl ureido, monohaloalkyl (C 1 -C 8) ureido, (C 1 -C 8) monoalkyl (mono (phenyl or naphthyl)) ureido, dialkyl (C 1 -C 8) ureido, di (phenyl or naphthyl) ureido, (haloalkyl (C1-C8) carbonyl) ureido, ureidoalq uilo (C1-C8), (C1-C8) monoalkyl ureidoalkyl (C1-C8), dialkyl (C1-C8) ureidoalkyl (C1-C8), mono (phenyl or naphthyl) ureidoalkyl (C1-C8), mono (phenyl or naphthyl) alkyl (C1-C8) ureidoalkyl (C1-C8), monohaloalkyl (C1-C8) ureidoalkyl (C1-C8), (haloalkyl) (C 1 -C 8)) (C 1 -C 8 alkyl) ureido (C 1 -C 8) alkyl, (C 1 -C 8) alkoxy (C 1 -C 8) carbonyl) ureido (C 1 -C 8) alkyl, glycinamide, mono (C 1 -C) alkyl 8) amino acid, aminocarbonylglycinamide, (aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, (C 1 -C 8 alkoxy) carbonylalkyl (C 1 -C 8) carbonyl) glycinamide, (C 1 -C 8 alkoxy) carbonylalkyl (C 1 -) C8) carbonyl), (phenyl or naph il) carbonylglycinamido, ((phenyl or naph il) carbonyl) (C 1 -C 8 alkyl) glycinamide, (mono (phenyl or naphthyl) alkyl) (C1-C8) aminocarbonyl) glycinamide, (mono (phenyl or naphthyl) alguil (C 1 -C 8) aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, (mono (phenyl or naphthyl) aminocarbonyl) glycinamide, (mono (phenyl or naphthyl) aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, glycinamidoalkyl (C1-C8), alaninamido, (C1-C8) monoalkyl alaninamido, alaninamido (C1-C8) alkyl, 3-15 membered heterocyclyl consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (C1-C8) alkyl; or R3 is a 3-15 membered heterocyclic ring system consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, substituted by one or more substituents independently selected from the group consisting of hydrogen , hydroxy, halo, (C 1 -C 8) alkyl, (C 1 -C 8) alkyl, suphonyl, (phenyl or naphthyl) sulfonyl, (C 1 -C 8) alkoxy, hydroxy (C 1 -C 8) alkoxy, (C 1 -C 8) haloalkyl, formyl, nitro, cyano, haloalkoxy (C1-C8), alkenyl (C2-C8), alkynyl (C2-C8), phenyl or naphthyl, (phenyl or naphthyl) alkyl (C1-C8), amino, mono-alkyl (C1-C8) amino , dialkyl (C 1 -C 8) amino, mono (phenyl or naphthyl) amino, mono (phenyl or naphthyl) alkyl (C 1 -C 8) amino, alkyl (C 1 -C 8) carbonylamino, alkoxy (C 1 -C 8) carbonylamino, alkenyl (C 2) -C8) carbonylamino, cycloalkyl (C3-C0) carbonylamino, (phenyl or naphthyl) carbonylamino, haloalkyl (C1-C8) carbonylamino, alkoxy (C1-C8) alkyl (C1-C8) carbonylamino, alkoxy (C1-C8) carbonylalkyl ( C1-C8) carbonylamino, (C 1 -C 8 alkylcarbonyl) (C 1 -C 8 alkyl) amino, (C 1 -C 8 alkoxycarbonyl) (C 1 -C 8 alkyl) amino, (C 1 -C 8) alkyl sulfonylamino, aminoalkyl (C 1 -) C8), (C1-C8) monoalkyl (C1-C8) aminoalkyl, (C1-C8) dialkylamino (C1-C8) alkyl, (C1-C8) alkylcarbonylamino (C1-C8) alkyl, (phenyl or naphthyl) carbonylaminoalkyl (C1 -C8), (C 1 -C 8 alkylcarbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (C 1 -C 8) alkoxy carbonylamino (C 1 -C 8) alkyl, carboxy, (C 1 -C 8) alkoxycarbonyl , (phenyl or naphthyl) (C1-C8) alkoxycarbonyl, (C1-C8) alkylcarbonyl, (phenyl or naphthyl) carbonyl, (phenyl or naphthyl) alkyl (C1-C8) carbonyl, aminocarbonyl, mono (C1-C8) alkyl aminocarbonyl, dialkyl (C1-C8) aminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, aminocarbonylalkyl (C1-C8), mono (C1-C8) alkyl aminocarbonylalkyl (C1-C8), dialkyl (C1-C8) aminocarbonylalkyl (C1-C8) , mono (phenyl or naphthyl) aminocarbonylalkyl (C 1 -C 8), guanidino, ureido, mono (C 1 -C 8) alkyl ureido, ureido (C 1 -C 8) alkyl, mono (C 1 -C 8) alkyl ureido (C 1 -C 8) alkyl, and glycinamide; R4 is -0-, -N (R7) -, -C (R8) 2- or a bond; R5 is an alkylene chain (C1-C8) or an alkylidene chain (C1-C8), or, if R4 is a bond, Rs is an alkylidene chain (C1-C8) optionally substituted by (phenyl or naphthyl) or -N ( R7) 2; R6 is -C (0) -, -C (S) -, -CH2- or a bond, - each R7 is independently selected from the group consisting of hydrogen, (C1-C8) alkyl, phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, (C1-C8) alkylcarbonyl, alkyl (C1-C8) carbonylalkyl (C1-C8), (phenyl or naphthyl) alkyl (C1-C8) carbonyl, (phenyl or naphthyl) alkyl (C1-C8) carbonylalkyl (C 1 -C 8), aminocarbonyl, (C 1 -C 8) monoalkylaminocarbonyl, dialkyl (C 1 -C 8) aminocarbonyl, and (C 1 -C 8) alkoxycarbonyl; and each R8 is independently selected from the group consisting of hydrogen, (C1-C8) alkyl, phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, hydroxy, (C1-C8) alkoxy, hydroxy (C1-C8) alkyl, (C1-C8) alkoxy (C1-C8) alkyl, amino, (C1-C8) aminoalkyl) amino , dialkyl (C1-C8) amino, alkyl (C 1 -C 8) carbonylamino, (C 3 -C 10) cycloalkyl carbonylamino, (C 3 -C 10) cycloalkyl (C 1 -C 8) alkyl carbonylamino, (C 1 -C 8) alkoxy carbonylamino, (C 1 -C 8) alkyl sulfonylaraine, (phenyl or naphthyl) carbonylamino, (C 1 -C 8) alkoxycarbonylalkyl (C 1 -C 8) carbonylamino, (C 1 -C 8 alkylcarbonyl) (C 1 -C 8 alkyl) amino, (phenyl or naphthyl) alkyl (C 1 -C 8) carbonylamino, (( phenyl or naphthyl) (C 1 -C 8) alkylcarbonyl) (C 1 -C 8 alkyl) amino, alkyl (C 1 -C 8) carbonylamino (C 1 -C 8) alkyl, (C 3 -C 10) cycloalkyl) carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8) alkoxy carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) carbonyl) ( (C 1 -C 8) alkyl) aminoalkyl _ (C 1 -C 8), (phenyl or naphthyl) alkyl (C 1 -C 8) carbonylamino (C 1 -C 8) alkyl, (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and carbonylaminoalkyl sulfur (C 1 -C 8), ( (phenyl or naphthyl) (C 1 -C 8) alkylcarbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (phenyl or naphthyl) sulfonylamino, (C1-C8) alkyl sulfonylamido (C1-C8) alkyl, ureido, (C1-C8) monoalkyl ureido, monohaloalkyl (C1-C8) ureido, dialkyl (Cl-C8) ureido, ureidoalkyl (C1- C8), (C1-C8) monoalkyl ureidoalkyl (C1-C8), dialkyl (C1-C8) ureidoalkyl (C1-C8), monohaloalkyl (C1-C8) ureidoalkyl (C1-C8), aminoalkyl (C1-C8), monoalkyl (C1-C8) (C1-C8) aminoalkyl, (C1-C8) dialkylamino (C1-C8) alkyl, (C1-C8) carboxyalkyl, (C1-C8) alkoxycarbonylalkyl (C1-C8), aminocarbonylalkyl (C1-C8) ), (C1-C8) monoalkylaminocarbonylalkyl (C1-C8), and dialkyl (C1-C8) aminocarbonylalkyl (C1-C8); with the proviso that when R4 is -N (R7) -, Rs is an alkylene chain (C1-C8) and Rs is -C (O) -, -C (S) -CH, R3 can not be a system of monocyclic saturated heterocyclic ring or forming a bridge containing 4-8 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 heterocyclic ring system forming a bridge containing 4-6 members consisting of carbon atoms and two nitrogen atoms , and with the proviso that when R3 is optionally substituted by phenyl, R4 is -0-, and R6 is another -C (O) -, -CH2- or a bond, Rs can not be an alkylene chain (C1-C8) ) branched; and with the proviso that when R4 is -0-, R5 is methylene, R6 is -C (0) -, R3 can not be optionally substituted flavonyl; and with the proviso that when R4 is -0-, Rs is methylene, Rs is -C (O) -, R3 can not be phenyl substituted by pyridazinonyl, and a single stereoisomer or a mixture thereof; or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable excipient. 34. The use of a compound of formula (Ib) as set forth in claim 33, for the preparation of a medicament for the treatment of an inflammatory disorder in a human, wherein the treatment comprises administering to a human in need of such treatment a therapeutically effective amount of such compound. 35. The use as described in claim 34, wherein the treatment comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (Ib) wherein: R3 is a carbocyclic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, (C 1 -C 8) alkyl, mercapto, mercaptoalkyl (C 1 -C 8), alkylthio (C 1 -C 8), alkyl (C 1 -C 8) sulfinyl, (C 1 -C 8) alkylsulphonyl, (phenyl or naphthyl) sulfonyl, (C 1 -C 8) alkylthio (C 1 -C 8) alkyl, (C 1 -C 8) alkyl sulfinylalkyl (C 1 -C 8), (C 1 -C 8) alkyl sulfonylalkyl (C 1) -C8), (C1-C8) alkoxy, (C1-C8) hydroxyalkoxy, (phenyl or naphthyl) oxy, (C1-C8) haloalkyl, formyl, formylalkyl (C1-C8), nitro, nitroso, cyano, (phenyl or naphthyl) (C1-C8) alkoxy, (C1-C8) haloalkoxy, (C1-C8) aminoalkoxy, (C3-C10) cycloalkyl, (C3-C10) cycloalkyl (C1-C8) alkyl, (hydroxy) cycloalkyl (C3-) C10) alkyl (C1-C8), (C3-C10) cycloalkyl amino, (C3-C10) cycloalkylamino (C1-C8) alkyl, (C1-C8) cyanoalkyl, alkenyl (C2-C8), (C2-C8) alkynyl, phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, (phenyl or naphthyl) alkenyl (C2-C8), hydroxyalkyl (C1-C8), (hydroxy) ) (phenyl or naphthyl) alkyl (Cl-C8), ((C 1 -C 8) monoalkyl) amino (phenyl or naphthyl) (C 1 -C 8) alkyl, (hydroxy (C1-C8) alkyl) thio (C1-C8) alkyl, hydroxyalkenyl (C2-C8), hydroxyalkynyl (C2-C8), (C1-C8) alkoxy (C1-C8) alkyl, (C 1 -C 8) alkoxy (phenyl or naphthyl) (C 1 -C 8) alkyl, (phenyl or naphthyl) oxyalkyl (C 1 -C 8), (phenyl or naphthyl) alkoxy (C 1 -C 8) alkyl (C 1 -C 8), amino, (C 1 -C 8) aminoalkyl, dialkyl (C 1 -C 8) amino, mono (phenyl or naphthyl) amino, mono (phenyl or naphthyl) alkyl (C 1 -C 8) amino, aminoalkyl (C 1 -C 8) C8) amino, (3-15 membered heterocyclyl which consists of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) amino, (C3-C10) cycloalkyl (C1-C8) alkyl amino), (C 1 -C 8) alkylcarbonylamino, (C 1 -C 8) alkoxycarbonylamino, (C 2 -C 8) alkenylcarbonylamino, (C 3 -C 10) cycloalkylcarbonylamino, (phenyl or naphthyl) carbonylamino, (3-15 membered heterocyclyl) consists of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylamino, (C1-C8) haloalkyl carbonylamino, (C1-C8) alkoxy (C1-C8) alkyl carbonylamino, alkoxy (C1 -C8) carbonylamino (C 1 -C 8) carbonylamino, (C 1 -C 8 alkyl) carbonyl) (C 1 -C 8 alkyl) amino, (C 1 -C 8 alkoxy) carbonyl (C 1 -C 8 alkyl) amino, alkyl (C1-C8) sulfonylamino, am (C1-C8) -noalkyl, (C1-C8) monoalkylamino (C1-C8) alkyl, (C1-C8) dialkylamino (C1-C8) aminoalkyl, (C1-C8) hydroxyalkyl (C1-C8) aminoalkyl, mono (phenyl) naphthyl) amino (C 1 -C 8) alkyl, mono (phenyl or naphthyl) alkyl (C 1 -C 8) ammonium (C 1 -C 8) alkyl, (C 1 -C 8) alkyl carbonylamino (C 1 -C 8) alkyl, (phenyl or naphthyl) carbonylaminoalkyl (C 1 - C8), (C 1 -C 8 alkyl) carbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (C 1 -C 8) alkyl amino (C 1 -C 8) alkyl, (C 1 -C 8) alkoxy carbonylaminoalkyl (C 1 -C 8), C 1 -C 8 alkoxycarbonylalkyl (C 1 -C 8) alkylcarbonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkoxycarbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, alkyl (C 1 -C 8) C 1 -C 8 alkyl sulfonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) sulfonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (phenyl or naphthyl) sulfonylaminoalkyl (C 1 -C 8) -C8), ((phenyl or naphthyl) sulfonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (3-15 membered heterocyclyl which consists of carbon atoms and from one to five selected heteroatoms) ions of the group consisting of nitrogen, oxygen and sulfur) amino (C 1 -C 8) alkyl, carboxy, (C 1 -C 8) alkoxycarbonyl, (phenyl or naphthyl) (C 1 -C 8) alkoxycarbonyl, (C 1 -C 8) alkylcarbonyl, (phenyl or naphthyl) carbonyl, (phenyl or naphthyl) alkyl (C 1 -C 8) carbonyl, (hydroxy (C 1 -C 8) alkoxy) carbonyl, carboxyalkyl (C 1 -C 8), alkoxy (C 1 -C 8) carbonylalkyl (C 1 -C 8), (phenyl or naphthyl) (C1-C8) alkoxycarbonylalkyl (C1-C8), alkoxy (C1-C8) alkyl (C1-C8) carbonyloxyalkyl (C1-C8), dialkyl (C1-C8) aminocarbonyloxyalkyl (C1-C8), (C 1 -C 8) alkyl carbonylalkyl (C 1 -C 8), (phenyl or naphthyl) carbonylalkyl (C 1 -C 8), (phenyl or naphthyl) alkyl (C 1 -C 8) carbonylalkyl (C 1 -C 8), aminocarbonyl, mono (C 1 -C 8) alkyl aminocarbonyl, dialkyl (C1-C8) aminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, mono (phenyl or naphthyl) alkyl (C1-C8) aminecarbonyl, (aminocarbonylalkyl (C1-C8)) aminocarbonyl, (mono (C1-C8) alkyl) aminocarbonylalkyl (C 1 -C 8) aminocarbonyl, (C 1 -C 8) alkylaminocarbonyl, (C 1 -C 8) alkoxycarbonylalkyl (C 1 -C 8) alkyl aminocarbonyl, (C 1 -C 8) aminocarbonyl aminocarbonyl, (hydroxyalkyl (C 1 -C 8) C8)) aminocarbonyl, aminocarbonylalkyl (C1-C8), monoalkyl (C1-C8) aminocarbonylalkyl (C1-C8), dialkyl (C1-C8) aminocarbonylalkyl (C1-C8), mono (phenyl or naphthyl) aminocarbonylalkyl (C1-C8) , mono (phenyl or naphthyl) alkyl (C1-C8) aminoc arbonylalkyl (C1-C8), amidino, hydroxyamidino, guanidino, ureido, (C1-C8) monoalkyl ureido, mono (phenyl or naphthyl) ureido, mono (phenyl or naphthyl) alkyl (Cl-C8) ureido, monohaloalkyl (C1-C8) ) ureido, ((C 1 -C 8) monoalkyl (mono (phenyl or naphthyl)) ureido, dialkyl (C 1 -C 8) ureido, di (phenyl or naph il) ureido, (haloalkyl (C 1 -C 8) carbonyl) ureido, ureidoalkyl (C1-C8), (C1-C8) monoalkyl ureidoalkyl (C1-C8), dialkyl (C1-C8) ureidoalkyl (C1-C8), mono (phenyl or naphthyl) ureidoalkyl (C1-C8), mono (phenyl or naphthyl) ) rent (C1-C8) ureidoalkyl (C1-C8), monohaloalkyl (C1-C8) ureidoalkyl (C 1 -C 8), (C 1 -C 8) haloalkyl (C 1 -C 8 alkyl) ureido (C 1 -C 8) alkyl, (C 1 -C 8) alkoxy (C 1 -C 8) carbonyl) ureido (C 1 -C 8) alkyl, glycinamide, (C1-C8) monoacyl glycinamide, aminocarbonylglycinamido, (C1-C8alkoxy) (C1-C8) alkylcarbonyl) glycinamide, (aminocarbonyl) (C1-C8alkyl) glycinamide, (C1-C8alkoxy) carbonylalkyl (C 1 -C 8) carbonyl) (C 1 -C 8 alkyl) glycinamide, (C 1 -C 8 alkoxy) carbonylamino (C 1 -C 8) alkylcarbonyl) glycinamide, (phenyl or naphthyl) carbonylglycinamide, ((phenyl or naphthyl) carbonyl) ( (C 1 -C 8) alkyl glycinamide, (mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonyl) glycinamide, (mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonyl) (C 1 -C 8 alkyl) glycinamide , (mono (phenyl or naphthyl) aminocarbonyl) glycinamide, (mono (phenyl or naphthyl) aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, glycinamido (C 1 -C 8) alkyl, alaninamide, (C 1 -C 8) monoalkyl alaninamide, alaninamidoalkyl ( C1-C8), 3-15 membered heterocyclyl consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) alkyl (C1) -C8) 36. Use as described in claim 35, wherein the treatment comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (Ib) wherein: R4 is -0-, -N ( R7) - or -C (R8) -; Rs is an (C1-C8) alkylene chain, - R7 is selected from the group consisting of hydrogen, (C1-C8) alkyl, phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, (C1-C8) alkyl carbonyl, (C 1 -C 8) alkylcarbonylalkyl (C 1 -C 8), (phenyl or naphthyl) alkyl (C1-C8) carbonyl, (phenyl or naphthyl) alkyl (C1-C8) carbonylalkyl (C 1 -C 8), aminocarbonyl, (C 1 -C 8) monoalkylaminocarbonyl, dialkyl (C 1 -C 8) aminocarbonyl, and (C 1 -C 8) alkoxycarbonyl; and each Rs is independently selected from the group consisting of hydrogen, (C1-C8) alkyl, phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, hydroxy, (C1-C8) alkoxy, hydroxyalkyl (C1- C8), (C1-C8) alkoxy (C1-C8) alkyl, amino, (C1-C8) aminoalkyl, dialkyl (C1-C8) amino, alkyl (C1-C8) carbonylamino, cycloalkyl (C3-C0) carbonylamino, (C3-C10) cycloalkyl (C1-C8) alkylcarbonylamino, (C 1 -C 8) alkoxy carbonylamino, (C 1 -C 8) alkyl sulfonylamino, (phenyl or naphthyl) carbonylamino, alkoxy (C 1 -C 8) carbonylalkyl (C 1 -C 8) carbonylamino, (C 1 -C 8 alkyl) carbonyl) (alkyl ( C1-C8)) amino, (phenyl or naphthyl) alkyl (C1-C8) carbonylamino, ((phenyl or naphthyl) alkyl (C1-C8) carbonyl) (C1-C8 alkyl) amino, (C1-C8) alkyl) carbonylaminoalkyl (C1-C8), cycloalkyl (C3-C10) carbonylaminoalkyl (C1-C8), alkoxy (C1-C8) carbonylaminoalkyl (C1-C8), (C1-C8alkyl) carbonyl) (C1-C8alkyl)) (C 1 -C 8) aminoalkyl, (phenyl or naphthyl) alkyl (C 1 -C 8) carbonylamino (C 1 -C 8) alkyl, (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylaminoalkyl (C 1 -C 8), ((phenyl or naphthyl) alkyl (C 1 -C 8) carbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (phenyl or naphthyl) sulfonylamino, alkyl (C1-C8) sulfonylamino (C1-C8) alkyl, ureido, (C1-C8) monoalkyl ureido, monohaloalkyl (C1-C8) ureido, dialkyl (C1-C8) ureido, ureidoalkyl (C1-C8), monoalkyl (C1-C8) ureidoalkyl (C1-C8), dialkyl (C1-C8) ureidoalkyl (C1-C8), monohaloalkyl ( C1-C8) ureidoalkyl (C1-C8), aminoalkyl (C1-C8), monoalkyl (C1-C8) aminoalkyl (C1-C8), dialkyl (C1-C8) aminoalkyl (C1-C8), carboxyalkyl (C1-C8) , (C 1 -C 8) alkoxycarbonylalkyl (C 1 -C 8), aminocarbonylalkyl (C 1 -C 8), (C 1 -C 8) monoalkyl aminocarbonylalkyl (C 1 -C 8), and dialkyl (C 1 -C 8) aminocarbonyl (C 1 -C 8) alkyl. 37. Use as described in claim 36, wherein the treatment comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (Ib) wherein: R4 is -O-; Rs is methylene; and R6 is -CÍO) -. 38. Use as described in claim 37, wherein the treatment comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (Ib) wherein: R 2 is one or more substituents selected independently from the group consisting of hydrogen and halo; R3 is phenyl optionally substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, (C1-C8) alkyl, (C1-C8) alkoxy, hydroxy (C1-C8) alkoxy, halo (C1-C8) alkyl , formyl, nitro, cyano, (C1-C8) aminoalkoxy, (C3-C10) cycloalkyl, (C3-C10) cycloalkyl (C1-C8) aminoalkyl, (phenyl or naphthyl) (C1-C8) alkyl, hydroxyalkyl (C1- C8), ((C1-C8) monoalkylamino) (phenyl or naphthyl) (C1-C8) alkyl, (C1-C8) alkoxy (C1-C8) alkyl, amino, (C1-C8) monoalkyl amino, dialkyl (C1 -C8) amino, mono (phenyl or naphthyl) alkyl (C1-C8) amino, alkyl (C1-C8) carbonylamino, (C2-C8) alkenyl carbonylamino, cycloalkyl (C3-CIO) carbonylamino, (phenyl or naphthyl) carbonylamino, (3-15 meierabros heterocyclyl which consists of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylamino, haloalkyl (C 1 -C 8) carbonylamino, (C 1 -C 8) alkoxy (C 1 -C 8) alkyl carbonylamino, (C 1 -C 8) alkoxy carbonylalkyl (C 1 -C 8) carbonylamino, (alkyl) (C 1 -C 8) carbonyl) (C 1 -C 8 alkyl) amino, (C 1 -C 8) alkyl sulfonylamino, (C 1 -C 8) aminoalkyl, (C 1 -C 8) monoalkyl (C 1 -C 8) alkyl, (C 1 -C 8) dialkyl amino (C1-C8) aminoalkyl, mono (phenyl or naphthyl) aminoalkyl (C1-C8), mono (phenyl or naphthyl) alkyl (C1-C8) aminoalkyl (C1-C8), alkyl (C1-C8) carbonylaminoalkylp (C1- C8), (phenyl or naphthyl) carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) carbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (C 1 -C 8) alkyl (amino) alkyl aminoalkyl ( C1-C8), (C1-C8) alkoxycarbonylaminoalkyl (C1-C8), (C1-C8) alkoxycarbonylalkyl (C1-C8) carbonylaminoalkyl (C1-C8), (C1-C8alkoxycarbonyl) (alkyl (C1 -C8)) amino (C 1 -C 8) alkyl, (C 1 -C 8) alkyl sulfonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) sulfonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (phenyl) or (naphthyl) sulfonylamino (C 1 -C 8) alkyl, ((phenyl or naphthyl) sulfonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (3-15 membered heterocyclyl consisting of carbon atoms and one to five hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur) amino (C 1 -C 8) alkyl, carboxy, coxy (Cl - C 8) carbonyl, alkyl (C 1 -C 8) carbonyl, (hydroxy (C 1 -C 8) alkoxy) carbonyl, aminocarbonyl , (C 1 -C 8) monoalkyl aminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, (aminocarbonylalkyl (C 1 -C 8) aminocarbonyl, (amino (C 1 -C 8) aminocarbonyl) aminocarbonyl, (hydroxy (C 1 -C 8) alkyl) aminocarbonyl, dialkyl (C 1 -C 8) -C8) aminocarbonylalkyl (C1-C8), hydroxyamidino, ureido, mono (C1-C8) ureido, ureido, mono (phenyl or naphthyl) ureido, mono (phenyl or naphthyl) alkyl (C1-C8) ureido, (mono-C1-C8alkyl) )) (mono (phenyl or naphthyl)) ureido, (C 1 -C 8) haloalkyl carbonyl) ureido, ureido (C 1 -C 8) alkyl, (C 1 -C 8) monoalkyl ureido (C 1 -C 8) alkyl, (C 1 -C 8) dialkyl ureidoalkyl (C1-C8), mono (phenyl or naphthyl) ureidoalkyl (C1-C8), mono (phenyl or naphthyl) alkyl (C1-C8) ureidoalkyl (C1-C8), monohaloalkyl (C1-C8) ureidoalkyl (C1-C8) , ((C 1 -C 8) haloalkyl (C 1 -C 8) alkyl) ureidoalkyl (C1-C8), (C1-C8 alkoxy) carbonylalkyl (C1-C8)) ureido (C1-C8) alkyl, glycinamide, (C1-C8) monoalkyl glycinamide, aminocarbonylglycinamide, (C1-C8 alkoxy) alkyl (C1- C8) carbonyl) glycinamide, (aminocarbonyl) - (C 1 -C 8 alkyl) glycinamide, (C 1 -C 8 alkoxy) carbonylalkyl (C 1 -C 8) carbonyl) (C 1 -C 8 alkyl) glycinamide, (C 1 -C 8 alkoxy) carbonylamino (C 1 -C 8) alkylcarbonyl) glycinamide, (phenyl or naph il) carbonylglycinamide, ((phenyl or naph il) carbonyl (rent) (C 1 -C 8)) glycinamide, (mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonyl) glycinamide, (mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, (mono (phenyl or naphthyl) aminocarbonyl) glycinamide, (mono (phenyl or naphthyl) aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, alaninamide, heterocyclyl of 3-15 mierabros consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur and (3-15 meracycloheterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur) (C 1 -C 8) alkyl. 39. The use as defined in claim 38, wherein the treatment comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (Ib) which is selected from the group consisting of the following compounds: - ((3,4, 5-trimethoxy-enoxo) methyl) carbonyl-4- (benzyl) piperazine; 1- ((3,5-dimethoxyphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2- (hydroxymethyl) phenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine, 1- ((4-iodophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) iperazine; 1- ((2-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-methylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2,4-dichlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-bromo-2-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-chloro-3-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-bromofenoxyl) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-bromofenoxi) methyl) carbonyl -4- (benzyl) piperazine, 1- ((2,4-dibromofonoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-f ormilf enoxi) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((2-methoxy-5-nitrophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3, 4, 5-trimethoxy-enoxy) methyl) carbonyl-4- (4-fluorobenzyl) piperazine; 1- ((4-chloro-enoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine;

1- ((4-chloro-enoxy) methyl) carbonyl -4- (4-f luorobenzyl) iperazine; 1- ((3-fluoro-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((3,5-dimethoxy-4-chlorophenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine; 1- ((4-bromo-2-forraylphenoxy) methyl) carbonyl-4- (4-chlorobenzyl) piperazine. 1- ((3-formyl-4-nitrophenoxy) methyl) carbonyl-4- (4-fluorobenzyl) piperazine; 1- ((2-aminocarbonyl-4-chlorophenoxy) methyl) carbonyl-4- (4-fluorobenzyl) piperazine; 1- ((3,5-dimethoxy-4-bromophenoxy) methyl) carbonyl-4- (4-fluorobenzyl) piperazine; and 1- ((2-acetylaminofenoxyl) methyl) carbonyl-4- (4-fluorobenzyl) piperazine.

40. A compound of the following formula (le) (le) wherein: Y is a pharmaceutically acceptable counterion: Rlb is one or more substituents independently selected from the group consisting of hydrogen, oxo, halo, (C 1 -C 8) alkyl, (C 3 -C 10) cycloalkyl, (C 3) cycloalkyl -C10) (C1-C8) alkyl, (C3-C10) cycloalkyl) amino (C1-C8) alkyl, (C3-C10 cycloalkyl) (C1-C8) alkyl) amino (C1-C8) alkyl, halo (C1-C8) alkyl , (C2-C8) alkenyl, (C2-C8) alkynyl, phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, (phenyl or naphthyl) alkenyl (C2-C8), formyl, formylalkyl (C1-C8) ), hydroxyalkyl (C1-C8), hydroxyalkenyl (C2-C8), hydroxyalkynyl (C2-C8), (hydroxy) (phenyl or naphthyl) alkyl (C1-C8), (hydroxy) cycloalkyl (C3-C10) alkyl (C1 -C8), mercaptoalkyl (C1-C8), cyano (C1-C8) alkyl, haloalkyl (C1-C8) carbonylaminoalkyl (C1-C8), (C1-C8-alkoxy) (phenyl or naphthyl) alkyl (C1-C8) , (C 1 -C 8) alkoxy (C 1 -C 8) alkyl, (phenyl or naphthyl) oxyalkyl (C 1 -C 8), (phenyl or naphthyl) (C 1 -C 8) alkoxy (C 1 -C 8) alkyl (C 1 -C 8) alkylthio (C 1 -C 8) alkyl, (C 1 -C 8) alkyl sulfinylalkyl (C 1 -C 8) alkyl (C 1 -C 8) sulfonylalkyl (C 1 -C 8), hydroxyalkyl (C 1 -C 8) thioalkyl (C 1 -C 8) ), (C 1 -C 8) aminoalkyl, (C 1 -C 8) aminoalkyl (C 1 -C 8) alkyl, (C 1 -C 8) dialkyl amino (C 1 -C 8) alkyl, mono (phenyl or naphthyl) amino (C 1 -C 8) alkyl, mono ( phenyl or naphthyl) (C 1 -C 8) alkyl amino (C 1 -C 8) alkyl, (C 1 -C 8) alkyl (C 1 -C 8) alkyl carbonylamino (C 1 -C 8) alkyl, (alkyl) (C 1 -C 8) carbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (C 1 -C 8) azidoalkyl, (C 1 -C 8) ureidoalkyl, monoalkyl (C1-C8) ureidoalkyl (C1-C8), dialkyl (C1-C8) ureidoalkyl (C1-C8), (C1-C8 alkoxy) carbonylalkyl (C1-C8)) ureidoalkyl (C1-C8), (C1-C8) alkoxycarbonylaminoalkyl (C1-C8), hydroxyalkyl (C1-C8) aminoalkyl (C1-C8), (phenyl or naphthyl) oxyalkyl (C1-C8) carbonyloxyalkyl (C1-C8), alkoxy (C1-C8) alkyl (C1-C8) carbonyloxyalkyl (C1-C8), (phenyl or naphthyl) alkoxy (C1-C8) alkyl (Cl-C8) carbonyloxyalkyl (C1-C8), alkyl (C 1 -C 8) carbonyl, (C 1 -C 8) alkylcarbonylalkyl (C 1 -C 8), carboxy, (C 1 -C 8) alkoxycarbonyl, (phenyl or naphthyl) (C 1 -C 8) alkoxycarbonyl, (phenyl or naphthyl) (C1-C8) alkylcarbonyl, aminocarbonyl, (C1-C8) monoalkylaminocarbonyl, dialkyl (C1-C8) aminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, mono (phenyl or naphthyl) alkyl (C1-C8) aminocarbonyl, carboxyalkyl (C1-C8), alkoxy (C1-C8) carbonylalkyl (C1-C8), (phenyl or naphthyl) alkoxy (C1-C8) carbonylalkyl (C1-C8), aminocarbonylalkyl (C1-C8), monoalkyl ( C1-C8) aminocarbonylalkyl (C1-C8), dialkyl (C1-C8) aminocarbonylalkyl (C1-C8), mono (phenyl or naphthyl) aminocarbonylalkyl (C1-C8), mono (phenyl or naphthyl) alkyl (C1-C8) aminocarbonylalkyl (C1-C8), (phenyl or naphthyl) sulfonyl, heterocyclyl of 3-15 mierabros consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and (3-15 membered heterocyclyl) which consists of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (C 1 -C 8) alkyl; R 2 is one or more substituents independently 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) alkyl, (C 1 -C 8) alkyl sulphonyl, (C 1 -C 8) alkyl, suphonyl, (C 1 -C 8) alkylthio (C 1 -C 8) alkyl, (C 1 -C 8) alkyl sulfinylalkyl (C 1 -C 8), (C 1 -C 8) alkyl sulfonylalkyl (C 1 -C 8), (C 1 -C 8) alkoxy, (phenyl or naphthyl) oxy, (C 1 -C 8) haloalkyl, formyl, formylalkyl (C 1 -C 8), nitro, nitroso, cyano, (phenyl or naphthyl) (C 1 -C 8) alkoxy, haloalkoxy ( C1-C8), (C3-C10) cycloalkyl, (C3-C10) cycloalkyl (C1-C8) alkyl, (hydroxy) (C3-C10) cycloalkyl (C1-C8) alkyl, (C3-C10) cycloalkyl amino, cycloalkyl (C3-C10) aminoalkyl (C1-C8), (cycloalkyl (C1-C8) alkyl) amino, (cycloalkyl (C3-C10) alkyl (C1-C8)) aminoalkyl (C1-C8), cyano (C1-C8) alkyl , (C2-C8) alkenyl, (C2-C8) alkynyl, phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, (phenyl or naphthyl) alkenyl (C2-C8), hydroxyalkyl (C1-C8), (hydroxy) (phenyl or naphthyl) alkyl (C1-C8), hydroxyalkyl (C1-C8) thioalkyl (C1-C8), hydroxyalkenyl- (C2-C8), hydroxyalkynyl (C2-C8), alkoxy (C1-C8) (C1-C8) alkyl, (C1-C8) alkoxy (phenyl or naphthyl) (C1-C8) alkyl, (phenyl or naphthyl) oxyalkyl (C1-C8), (phenyl or naphthyl) alkoxy (C1-C8) (C1-C8) alkyl, amino, (C1-C8) aminoalkyl, dialkyl (C1-C8) amino, mono-phenyl or naphthyl) amino, mono (phenyl or naphthyl) alkyl (C1-C8) amino , (C 1 -C 8) aminoalkyl, (C 1 -C 8) aminoalkyl (C 1 -C 8) alkyl, (C 1 -C 8) dialkyl amino (C 1 -C 8) alkyl, (C 1 -C 8) hydroxyalkyl (C 1 -C 8) alkyl, mono (phenyl) or naphthyl) (C1-C8) aminoalkyl, mono (phenyl or naphthyl) alkyl (C1-C8) aminoalkyl (C1-C8), alkyl (C1-C8) carbonylamino, (C1-C8 alkyl) carbonyl) (alkyl (C1 -C8)) amino, (C 1 -C 8) alkyl carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) carbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (C 1 -C 8) alkoxy carbonylamino , (C 1 -C 8 alkoxy) carbonyl) (C 1 -C 8 alkyl) amino, (C 1 -C 6) alkoxy 8) carbonylaminoalkyl (C 1 -C 8), (C 1 -C 8 alkoxycarbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, carboxy, (C 1 -C 8) alkoxycarbonyl, (phenyl or naphthyl) alkoxy ( C1-C8) carbonyl, (C 1 -C 8) alkylcarbonyl, (C 1 -C 8) alkylcarbonylalkyl (C 1 -C 8), (phenyl or naphthyl) carbonyl, (phenyl or naphthyl) carbonylalkyl (C 1 -C 8), (phenyl or naphthyl) ) (C1-C8) alkylcarbonyl, (phenyl or naphthyl) alkyl (C 1 -C 8) carbonylalkyl (C 1 -C 8), carboxyalkyl (C 1 -C 8), alkoxy (C 1 -C 8) carbonylalkyl (C 1 -C 8), (phenyl or naphthyl) alkoxy (C 1 -C 8) carbonylalkyl (C1-C8), alkoxy (C1-C8) alkyl (C1-C8) carbonyloxyalkyl (C1-C8), aminocarbonyl, mono (C1-C8) alkylaminocarbonyl, dialkyl (C1-C8) aminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, mono (phenyl or naphthyl) alkyl (C1-C8) aminocarbonyl, aminocarbonylalkyl (C1-C8), monoalkyl (C1-C8) aminocarbonylalkyl (C1-C8), dialkyl (C1-C8) aminocarbonylalkyl (C1-C8), mono (phenyl or naphthyl) aminocarbonylalkyl (C 1 -C 8), mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonylalkyl (C 1 -C 8), amidino, guanidino, ureido, (C 1 -C 8) monoalkyl ureido, dialkyl (C 1 -C 8) ) ureido, ureidoalkyl (C1-C8), (C1-C8) monoalkyl ureido (C1-C8) alkyl, dialkyl (C1-C8) ureidoalkyl (C1-C8), heterocyclyl of 3-15 members which consists of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen or, oxygen and sulfur and (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (C1-C8) alkyl, - R3 is a carbocyclic ring substituted by one or more substituents independently 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, alkyl (C 1 -) C8) sulfinyl, (C1-C8) alkyl, suphonyl, (phenyl or naphthyl) sulfonyl, alkyl (C1-C8) thioalkyl (C1-C8), alkyl (C1-C8) sulfinylalkyl (C1-C8), alkyl (C1-C8) ) sulfonylalkyl (C1-C8), alkoxy (C1-C8), hydroxyalkoxy (C1-C8), (phenyl or naphthyl) oxy, haloalkyl (C1-C8), formyl, formylalkyl (C1-C8), nitro, nitroso, cyano , (phenyl or naphthyl) (C1-C8) alkoxy, (C1-C8) haloalkoxy, (C1-C8) aminoalkoxy, (C3-C10) cycloalkyl, (C3-C10) cycloalkyl (C1-C8) alkyl, (hydroxy) (C3-C10) cycloalkyl (C1-C8) alkyl, cyclone o-alkyl (C3-C10) amino, (C3-cycloalkyl) aminoalkyl (C1-C8), cyano (C1-C8) alkyl, alkenyl (C2-C8), alkynyl (C2-C8), phenyl or naphthyl, (phenyl or naphthyl) ) (C 1 -C 8) alkyl, (phenyl or naphthyl) alkenyl (C 2 -C 8), hydroxyalkyl (C 1 -C 8), (hydroxy) (phenyl or naphthyl) alkyl (C 1 -C 8), (mono (C 1 -C 8) alkyl) amino ) (phenyl or naphthyl) (C1-C8) alkyl, (C1-C8) hydroxyalkyl (C1-C8) alkyl, (C2-C8) hydroxyalkenyl, (C2-C8) hydroxyalkynyl, (C1-C8) alkoxy alkyl ( C1-C8), (C1-C8 alkoxy) (phenyl or naphthyl) alkoyl (C1-C8), (phenyl or naphthyl) oxyalkyl (C1-C8), (phenyl or naphthyl) alkoxy (C1-C8) alkyl ( C1-C8), amino, (C1-C8) aminoalkyl, dialkyl (C1-C8) amino, mono (phenyl or naphthyl) amino, mono (phenyl or naphthyl) alkyl (C1-C8) amino, aminoalkyl (C1-C8) amino) (3-15 membered heterocyclyl consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) amino, (C3-CIO) alkyl (C1-C8) alkyl) A.M or (C 1 -C 8) alkylcarbonylamino, (C 1 -C 8) alkoxycarbonylamino, (C 2 -C 8) alkenylcarbonylamino, (C 3 -CIO) carbonylamino (phenyl or naphthyl) carbonylamino cycloalkyl, (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylamino, (C1-C8) haloalkyl carbonylamino, (C1-C8) alkoxy (C1-C8) alkylcarbonylamino, (C1-6) alkoxy C8) carbonylamino (C1-C8) carbonylamino, (C1-C8 alkyl) carbonyl) (C1-C8 alkyl) amino, (C1-C8 alkoxy) carbonyl) (C1-C8 alkyl) amino, alkyl ( C1-C8) sulfonylamino, (C1-C8) aminoalkyl, (C1-C8) monoalkylamino (C1-C8) alkyl, (C1-C8) dialkylamino (C1-C8) alkyl, (C1-C8) hydroxyalkyl (C1-C8) aminoalkyl ), mono (phenyl or naphthyl) aminoalkyl (C1-C8), mono (phenyl or naphthyl) aminoalkyl (C1-C8), alkyl (C1-C8) carbonylaminoalkyl (C1-C8), (phenyl or naphthyl) carbonylaminoalkyl (C1- C8), (C 1 -C 8 alkyl) carbonyl) (C 1 -C 8 alkyl) aminoalkyl (C 1 -C 8) (C 1 -C 8 cycloalkylalkyl) amino (C 1 -C 8) alkoxy (C 1 -C 8) alkoxycarbonylamino (C 1 -C 8) alkyl (C 1 -C 8) alkoxycarbonylalkyl (C 1 -C 8) carbonylaminoalkyl (C 1 -C 8) ( (C 1 -C 8) alkoxycarbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl (C 1 -C 8) alkylsulfonylamino (C 1 -C 8) alkyl, (alquil (C 1 -C 8) sulfonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (phenyl or naphthyl) sulfonylamino (C 1 -C 8) alkyl, ((phenyl or naphthyl) sulfonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8 &) alkyl, (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur) aminoalkyl (C 1 -C 8) -C8), carboxy, (C1-C8) alkoxycarbonyl, (phenyl or naphthyl) (C1-C8) alkoxycarbonyl, (C1-C8) alkylcarbonyl, (phenyl or naphthyl) carbonyl, (phenyl or naphthyl) alkyl (C1 -C8) carbonyl, (hydroxy (C1-C8) alkoxy) carbonyl, carboxyalkyl (C1-C8), alkoxy (C1-C8) carbonylalkyl (C1-C8), (phenyl or naphthyl) alkoxy (C1-C8) carbonylalkyl (C1- C8), (C1-C8) alkoxy (C1-C8) alkyl carbonyloxyalkyl (C1-C8), dialkyl (C1-C8) aminocarbonyloxyalkyl (C1-C8), alkyl (C1-C8) carbonylalkyl (C1-C8), (phenyl) or naphthyl) carbonylalkyl (C 1 -C 8), (phenyl or naphthyl) alkyl (C 1 -C 8) carbonylalkyl (C 1 -C 8), aminocarbonyl, mono (C 1 -C 8) alkyl aminocarbonyl, dialkyl (C 1 -C 8) aminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonyl, (aminocarbonylalkyl (C 1 -C 8)) aminocarbonyl, (C 1 -C 8) monoalkyl aminocarbonylalkyl (C 1 -C 8) alkyl aminocarbonyl, (carboxyalkyl) (C 1 -C 8)) aminocarbonyl, (C 1 -C 8 alkoxy) carbonylalkyl (C 1 -C 8) aminocarbonyl, (C 1 -C 8) aminocarbonyl aminocarbonyl, (hydroxy (C1-C8) alkyl) aminocarbonyl, aminocarbonylalkyl (C1-C8), (C1-C8) monoalkylaminocarbonylalkyl (C1-C8), dialkyl (C1-C8) aminocarbonylalkyl (C1-C8), mono (phenyl or naphthyl) aminocarbonylalkyl (C1-C8), mono (phenyl or naphthyl) ) (C 1 -C 8) alkyl aminocarbonylalkyl (C 1 -C 8), amidino, hydroxyamidino, guanidino, ureido, (C 1 -C 8) monoalkyl ureido, mono (phenyl or naphthyl) ureido, mono (phenyl or naphthyl) alkyl (Cl-C8) ureido, monohaloalkyl (C1-C8) ureido, (mono (C1-C8) alkyl)) (mono (phenyl or naphthyl)) ureido, dialkyl (C1-C8) ureido, di (phenyl or naphthyl) ureido, (haloalkyl (C1-C8) carbonyl) ureido, ureidoalkyl (C1-C8), mono (C1-C8) alkyl) ureidoalkyl (C1-C8), dialkyl (C1-C8) ureidoalkyl (C1-C8), mono (phenyl or naphthyl) ureidoalkyl (C1-C8), mono (phenyl or naphthyl) alkyl (C1-C8) ureidoalkyl (C1-C8), monohaloalkyl (C1-C8) ureidoalkyl (C1-C8), (C1-C8) haloalkyl (C1-C8 alkyl) ureidoalkyl (C1-C8), (C1-C8 alkoxy) carbonylalkyl (C1-C8)) ureidoalkyl (C1-C8), glycinamide, (C1-C8) monoalkyl glycinamide, aminocarbonylglycinamide, (C1-C8 alkoxy) alkyl (C1-C8) carbonyl) glycinamide, (aminocarbonyl) (C1-C8 alkyl) glycinamide, (C 1 -C 8 alkoxycarbonylalkyl (C 1 -C 8) carbonyl) (C 1 -C 8 alkyl) glycinamide, (C 1 -C 8 alkoxy) carbonylamino (C 1 -C 8) alkylcarbonyl) glycinamide, (phenyl or naphthyl) carbonylglycinamide, ( (phenyl or naphthyl) carbonyl) (C 1 -C 8 alkyl) glycinamide, (mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonyl) glycinamide, (mono (phenyl or naphthyl) (C 1 -C 8) alkyl aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, (mono (phenyl or naphthyl) aminocarbonyl) glycinamide, (mono (phenyl or naphthyl) aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, glycinamide (C 1 -C 8) alkyl, alaninamide, (C 1 -C 8) monoalkyl alaninamide, alaninamido (C 1 -C 8) alkyl, 3-15 membered heterocyclyl consists of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur and (3-15 merazoyl heterocyclyl consisting of carbon atoms, and from one to five heteroatoms selected from the group consisting of nitrogen , oxygen and sulfur) (C 1 -C 8) alkyl; or R3 is a 3-15 membered heterocyclic ring system consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, (C1-C8) alkyl, alkyl (C1-C8) Suphonyl, (phenyl or naphthyl) sulfonyl, (C1-C8) alkoxy, hydroxyalkoxy (C1-C8), haloalkyl (C1-C8), formyl, nitro, cyano, haloalkoxy (C1-C8), alkenyl (C2-C8), alkynyl (C2-C8), phenyl or naphthyl, (phenyl or naphthyl) alkyl (C1-C8), amino, monoalkyl (C1- C8) amino, (C1-C8) dialkyl amino, mono (phenyl or naphthyl) amino, mono (phenyl or naphthyl) alkyl (C1-C8) amino, (C1-C8) alkyl carbonylamino, (C1-C8) alkoxy carbonylamino, alkenyl (C2-C8) carbonylamino, cycloalkyl (C3-C0) carbonylamino, (phenyl or naphthyl) carbonylamino, haloalkyl (C1-C8) carbonylamino, coxy (C1-C8) alkyl (C1-C8) carbonylamino, alkoxy ( C1-C8) carbonylalkyl (C1-C8) carbonylamino, (C1-C8 alkyl) carbonyl) (C1-C8 alkyl) amino, (C1-C8 alkoxy) carbonyl) (C1-C8 alkyl) amino, (C 1 -C 8) alkylsulfonylamino, (C 1 -C 8) aminoalkyl, (C 1 -C 8) monoalkylamino (C 1 -C 8) alkyl, (C 1 -C 8) dialkylamino (C 1 -C 8) alkyl, (C 1 -C 8) alkylcarbonylaminoalkyl (C 1) -C8), (phenyl or naphthyl) carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) carbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (C 1 -C 8) alkoxy carbonylaminoalkyl ilo (C 1 -C 8), carboxy, (C 1 -C 8) alkoxycarbonyl, (phenyl or naphthyl) (C 1 -C 8) alkoxycarbonyl, (C 1 -C 8) alkylcarbonyl, (phenyl or naphthyl) carbonyl, (phenyl or naphthyl) (C 1 -C 8) alkylcarbonyl, aminocarbonyl, (C 1 -C 8) monoalkyl aminocarbonyl, dialkyl (C 1 -C 8) aminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, aminocarbonylalkyl (C 1 -C 8), (C 1 -C 8) monoalkylaminocarbonylalkyl (C 1 -C 8), dialkyl (C 1 -C 8) aminocarbonylalkyl (C 1 -C 8), mono (phenyl or naphthyl) aminocarbonylalkyl (C 1 -) C8), guanidino, ureido, (C1-C8) monoalkyl ureido, ureidoalkyl (C1-C8), monoalkyl (C1-C8) ureidoalkyl (C1-C8), and glycinamide; R4 is -O-N (R7) -, -C (R8) 2- or a bond, - R5 is an alkylene chain (C1-C8) or an alkylidene chain (C1-C8), or, if R4 is a bond , Rs is an alkyl (C1-C8) chain optionally substituted by (phenyl or naphthyl) or -N (R7) 2; Rs is -C (0) -, -C (S) -, -CH2- or a bond; each R7 is independently selected from the group consisting of hydrogen, (C1-C8) alkyl, phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, (C1-C8) alkylcarbonyl, alkyl (C1-C8) carbonylalkyl (C1-C8), (phenyl or naphthyl) alkyl (C1-C8) carbonyl, (phenyl or naphthyl) alkyl (C1-C8) carbonylalkyl (C1-C8), aminocarbonyl, (C1-C8) monoalkylaminocarbonyl, dialkyl (C1-C8) aminocarbonyl, and (C1-C8) alkoxycarbonyl, each R8 is independently selected from the group consisting of hydrogen, (C1-C8) alkyl ), phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, hydroxy, (C1-C8) alkoxy, hydroxy (C1-C8) alkyl, (C1-C8) alkoxy (C1-C8) alkyl, amino, (C1-C8) aminoalkyl) amino , dialkyl (C1-C8) amino, alkyl (C 1 -C 8) carbonylamino, cycloalkyl (C 3 -CIO) carbonylamino, cycloalkyl (C 3 -C 10) alkyl (C 1 -C 8) carbonylamino, alkoxy (C 1 -C 8) carbonylamino, alkyl (C 1 -C 8) sulfonylamino, (phenyl or naphthyl) carbonylamino, (C 1 -C 8) alkoxycarbonylalkyl (C 1 -C 8) carbonylamino, (C 1 -C 8 alkylcarbonyl) (C 1 -C 8 alkyl) amino, (phenyl or naphthyl) alkyl (C 1 -C 8) carbonylamino, (( phenyl or naphthyl) (C 1 -C 8) alkylcarbonyl) (C 1 -C 8 alkyl) amino, alkyl (C1-C8) carbonylaminoalkyl (C1-C8), cycloalkyl (C3-C10) carbonylaminoalkyl (C1-C8), alkoxy (C1-C8) carbonylaminoalkyl (C1-C8), (C1-C8alkyl) carbonyl) (alkyl) (C1-C8)) (C1-C8) aminoalkyl, (phenyl or naphthyl) alkyl (C1-C8) carbonylamino (C1-C8) alkyl, (3-15 membered heterocyclyl consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylaminoalkyl (C1-C8), ((phenyl or naphthyl) alkyl (C 1 -C 8) carbonyl) (C 1 -C 8 alkyl) aminoalkyl (C1-C8), (phenyl or naphthyl) sulfonylamino, (C1-C8) alkyl sulfonylamino (C1-C8) alkyl, ureido, (C1-C8) monoalkyl ureido, monohalo (C1-C8) alkyl ureido, dialkyl (C1-C8) ureido, ureidoalkyl (C1-C8), monoalkyl (C1-C8) ureidoalkyl (C1-C8), dialkyl (C1-C8) ureidoalkyl (C1-C8), monohaloalkyl (C1-C8) ureidoalkyl (C1-C8), aminoalkyl (C1-C8), monoalkyl (C1-C8) aminoalkyl (C1-C8), dialkyl (C1-C8) aminoalkyl (C1-C8), carboxyalkyl (C1-C8), alkoxy (C1-C8) carbonylalkyl (C1-C8), aminocarbonylalkyl (C1-C8), monoalkyl (C1-C8) aminocarbonylalkyl (C1-C8), and dialkyl (C1 -C8) aminocarbonyl (C1-C8) alkyl; and R9 is (C1-C8) alkyl, (phenyl or naphthyl) alkyl (C1-C8), haloalkyl (C1-C8), hydroxyalkyl (C1-C8), alkoxy (C1-C8) alkyl (C1-C8), carboxyalkyl (C1-C8), alkoxy (Cl-C8) carbonylalkyl (C1- C8), rent (C1 - C 8) carbon on the one (C 1 - C 8), on which (C1-C8) carbonylaminoalkyl (C1-C8), aminocarbonylalkyl (C1-C8), (C1-C8) monoalkylaminocarbonylalkyl (C1-C8), dialkyl (C1-C8) aminocarbonylalkyl (C1-C8), (heterocyclyl

3-15 members consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (C 1 -C 8) alkyl, or (C 3 -C 10) cycloalkyl) alkyl (C1-C8), - with the proviso that when R4 is -N (R7) -, R3 can not be a

4- to 8-member heterocyclic ring system consisting of carbon atoms and only one nitrogen atom, and a single stereoisomer or a mixture thereof; or a pharmaceutically acceptable salt thereof. 41. A pharmaceutical composition useful in the treatment of an inflammatory disorder, which composition comprises a therapeutically effective amount of a compound as described in claim 40. 42. The use of a compound as described in claim 40, for the preparation of a medicament for the treatment of an inflammatory disorder in a human, wherein the treatment comprises administering to a human in need of such treatment a therapeutically effective amount of such a compound 43. A compound of the following formula (Id): wherein: R1b is one or more substituents independently selected from the group consisting of hydrogen, oxo, halo, (C1-C8) alkyl, (C3-C10) cycloalkyl, (C3-C10) cycloalkyl (C1-C8) alkyl, (C3-C10) cycloalkyl (C1-C8) aminoalkyl, (C3-C10) cycloalkyl (C1-C8) alkyl) amino (C1-C8) alkyl, halo (C1-C8) alkyl, (C2-C8) alkenyl, alkynyl ( C2-C8), phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, (phenyl or naphthyl) alkenyl (C2-C8), formyl, formylalkyl (C1-C8), hydroxyalkyl (C1-C8), hydroxyalkenyl (C2-C8), hydroxyalkynyl (C2-C8), (hydroxy) (phenyl or naphthyl) alkyl (C1-C8), (hydroxy) (C3-C10) alkyl (C1-C8) alkyl, mercapto (C1-C8) alkyl , (C 1 -C 8) cyanoalkyl, (C 1 -C 8) haloalkyl carbonylaminoalkyl (C1-C8), (C1-C8) alkoxy (phenyl or naphthyl) (C1-C8) alkyl, (C1-C8) alkoxy (C1-C8) alkyl, (phenyl or naphthyl) oxyalkyl (C1-C8), (phenyl or naphthyl) (C1-C8) alkoxy (C1-C8) alkyl, (C1-C8) alkylthio (C1-C8) alkyl, (C1-C8) alkyl sulfinylalkyl (C1-C8), (C1-C8) alkyl sulfonylalkyl (C1-C8), hydroxyalkyl (C1-C8) thioalkyl (C1-C8), aminoalkyl (C1-C8), monoalkyl (C1-C8) aminoalkyl (C1-C8), dialkyl (C1-C8) aminoalkyl (C1-C8), mono (phenyl or naphthyl) aminoalkyl (C1-C8), mono (phenyl or naphthyl) alkyl (C1-C8) aminoalkyl (C1-C8), alkyl (C 1 -C 8) carbonylaminoalkyl (C 1 -C 8), (C 1 -C 8 alkyl) carbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (C 1 -C 8) azidoalkyl, (C 1 -C 8) ureidoalkyl, (C 1 -C 8) monoalkyl ureido (C 1 -C 8) alkyl, (C 1 -C 8) dialkyl ureidoalkyl ( C1-C8), (C1-C8 alkoxy) carbonylalkyl (C1-C8)) ureidoalkyl (C1-C8), alkoxy (C1-C8) carbonylaminoalkyl (C1-C8), hydroxyalkyl (C1-C8) aminoalkyl (C1-C8) ), (phenyl or naphthyl) oxyalkyl (C1-C8) carbonyloxyalkyl. (C1-C8), (C1-C8) alkoxy alkyl (C1-C8) carbonyloxyalkyl (C1-C8), (phenyl or naphthyl) alkoxy (C1-C8) alkyl (C1-C8) carbonyloxyalkyl (C1-C8), alkyl (C 1 -C 8) carbonyl, (C 1 -C 8) alkylcarbonylalkyl (C 1 -C 8), carboxy, (C 1 -C 8) alkoxycarbonyl, (phenyl or naphthyl) (C 1 -C 8) alkoxycarbonyl, (phenyl or naphthyl) (C 1 -C 8) alkylcarbonyl, aminocarbonyl, (C 1 -C 8) monoalkylaminocarbonyl, dialkyl (C 1 -C 8) aminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, mono (phenyl or naphthyl) alkyl (C 1 -) C8) aminocarboralo, carboxyalkyl (C1-C8), alkoxy (C1-C8) carbonylalkyl (C1-C8), (phenyl or naphthyl) alkoxy (C1-C8) carbonylalkyl (C1-C8), aminocarbonylalkyl (C1-C8), monoalkyl (C 1 -C 8) aminocarbonylalkyl (C 1 -C 8), dialkyl (C 1 -C 8) aminocarbonylalkyl (C 1 -C 8), mono (phenyl or naphthyl) aminocarbonylalkyl (C 1 -C 8), mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonylalkyl (C1-C8), (phenyl or naphthyl) sulfonyl, heterocyclyl of 3-15 members consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and (heterocyclyl 3-15) members consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) (C 1 -C 8) alkyl, - R 3 is an anion system carbocyclic substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, (C 1 -C 8) alkyl, mercapto, (C 1 -C 8) mercaptoalkyl, alkylthio (C1-C8), (C1-C8) alkyl sulfinyl, (C1-C8) alkyl, suphonyl, (phenyl or naphthyl) sulfonyl, (C1-C8) alkylthio (C1-C8) alkyl, (C1-C8) alkyl sulfinylalkyl ( C1-C8), alkyl (C1-C8) sulfonylalkyl (C1-C8), (C1-C8) alkoxy, (C1-C8) hydroxyalkoxy, (phenyl or naphthyl) oxy, (C1-C8) haloalkyl, formyl, formylalkyl (C1-C8), nitro, nitroso, cyano, ( phenyl or naphthyl) (C1-C8) alkoxy, haloalkoxy (C1-C8), (C1-C8) aminoalkoxy, (C3-C10) cycloalkyl, (C3-C10) cycloalkyl (C1-C8) alkyl, (hydroxy) (C3-C10) cycloalkyl (C1-C8) alkyl, cycloalkyl (C3-77-.0) amino, (C3-C10) cycloalkyl (C1-C8) aminoalkyl, (C1-C8) cyanoalkyl, alkenyl (C2-C8), (C2-C8) alkynyl, phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, '(phenyl or naphthyl) alkenyl (C2-C8), hydroxyalkyl (C1-C8), ( hydroxy) (phenyl or naphthyl) alkyl (C1-C8), ((C1-C8) monoalkyl) amino (phenyl or naphthyl) alkyl (C 1 -C 8), (C 1 -C 8 hydroxyalkyl) thio (C 1 -C 8) alkyl, (C 2 -C 8) hydroxyalkenyl, (C 2 -C 8) hydroxyalkynyl, (C 1 -C 8) alkoxy (C 1 -C 8) alkyl, (alkoxy) (C1-C8)) (phenyl or naphthyl) (C1-C8) alkyl, (phenyl or naphthyl) oxyalkyl (C1-C8), (phenyl or naphthyl) (C1-C8) alkoxy (C1-C8) alkyl, amino, monoalkyl. (C 1 -C 8) amino, (C 1 -C 8) dialkyl amino, mono (phenyl or naphthyl) amino, mono (phenyl or naphthyl) alkyl (C 1 -C 8) amino, amino (C 1 -C 8) aminoalkyl, (heterocyclyl 3-) 15 merobes consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) amino, (C3-C10) cycloalkyl (C1-C8) alkyl) amino, (C1-C8) alkyl carbonylamino, (C 1 -C 8) alkoxy carbonylamino, (C 2 -C 8) alkenyl carbonylamino, (C 3 -CIO) carbonylamino cycloalkyl, (phenyl or naphthyl) carbonylamino, (3-15 membered heterocyclyl consisting of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) carbonylamino, haloalkyl (C 1 -C 8) carbonylamino, (C 1 -C 8) alkoxy (C 1 -C 8) alkyl carbonylamino, (C 1 -C 8) alkoxy carbonylalkyl (C 1 -C 8) carbonylamino, (C 1 -C 8 alkyl) carbonyl) (C 1 -C 8 alkyl) )) amino, (C 1 -C 8) alkoxycarbonyl) (C 1 -C 8 alkyl) amino, (C 1 -C 8) alkyl sulfonylamino, (C 1 -C 8) aminoalkyl, (C 1 -C 8) aminoalkyl (C 1 -C 8) alkyl , (C1-C8) dialkyl (C1-C8) aminoalkyl, (C1-C8) hydroxyalkyl (C1-C8) aminoalkyl, mono (phenyl or naphthyl) amino (C1-C8) alkyl, mono (phenyl or naphthyl) alkyl (C1- C8) amino (C 1 -C 8) alkyl, (C 1 -C 8) alkyl carbonylamino (C 1 -C 8) alkyl, (phenyl or naphthyl) carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) carbonyl) (C 1 -C 8 alkyl) ) (C 1 -C 8) aminoalkyl, (C 3 -C 10) alkyl (C 1 -C 8) alkyl) amino (C 1 -C 8) alkyl, (C 1 -C 8) alkoxy carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8) alkoxycarbonylalkyl C1-C8) carbonylaminoalkyl (C1-C8), (C1-C8alkoxy) carbonyl) (C1-C8alkyl)) aminoalkyl (C1-C8), alkyl (C1-C8) sulfonylaminoalkyl (C1-C8), (alkyl) (C1-C8) sulfonyl) (C1-C8 alkyl) a (C 1 -C 8) -minoalkyl, (phenyl or naphthyl) sulfonylamino (C 1 -C 8) alkyl, ((phenyl or naphthyl) sulfonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (3-15 membered heterocyclyl which consists of carbon atoms and one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) amino (C 1 -C 8) alkyl, carboxy, (C 1 -C 8) alkoxycarbonyl, (phenyl or naphthyl) (C 1 -C 8) alkoxy carbonyl, (C1-C8) alkylcarbonyl, (phenyl or naphthyl) carbonyl, (phenyl or naphthyl) alkyl (C1-C8) carbonyl, (hydroxy (C1-C8) alkoxy) carbonyl, carboxyalkyl (C1-C8), alkoxy ( C1-C8) carbonylalkyl (C1-C8), (phenyl or naphthyl) alkoxy (C1-C8) carbonylalkyl (C1-C8), alkoxy (C1-C8) alkyl (C1-C8) carbonyloxyalkyl (C1-C8), dialkyl ( C1-C8) aminocarbonyloxyalkyl (C1-C8), alkyl (C1-C8) carbonylalkyl (C1-C8), (phenyl or naphthyl) carbonylalkyl (C1-C8), (phenyl or naphthyl) alkyl (C1-C8) carbonylalkyl (C1-C8), aminocarbonyl, (C1-C8) monoalkylaminocarbonyl, dialkyl (C 1 -C 8) aminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, mono (phenyl or naphthyl) alkyl (C 1 -C 8) aminocarbonyl, (aminocarbonylalkyl (C 1 -C 8)) aminocarbonyl, (C 1 -C 8) monoalkyl aminocarbonylalkyl (C 1 -C 8) alkyl aminocarbonyl, (carboxyalkyl) (C 1 -C 8)) aminocarbonyl, (C 1 -C 8 alkoxy) carbonylalkyl (C 1 -C 8) aminocarbonyl, (C 1 -C 8) aminocarbonyl aminocarbonyl, (C 1 -C 8 hydroxyalkyl) aminocarbonyl, aminocarbonylalkyl (C1-C8), (C1-C8) monoalkylaminocarbonylalkyl (C1-C8), dialkyl (C1-C8) aminocarbonylalkyl (C1-C8), mono (phenyl or naphthyl) aminocarbonylalkyl (C1-C8), mono (phenyl or naphthyl) ) rent (C 1 -C 8) aminocarbonylalkyl (C 1 -C 8), amidino, hydroxyamidino, guanidino, ureido, mono (C 1 -C 8) alkyl ureido, mono (phenyl or naphthyl) ureido, mono (phenyl or naphthyl) alkyl (C 1 -C 8) ureido, monohaloalkyl (Cl-C8) ureido, ((C1-C8) monoalkyl) (mono (phenyl or naphthyl)) ureido, dialkyl (C1-C8) ureido, di (phenyl or naphthyl) ureido, (haloalkyl (C1-C8) carbonyl) ) ureido, ureidoalkyl (C1-C8), monoalkyl (C1-C8) ureidoalkyl (C1-C8), dialkyl (C1-C8) ureidoalkyl (C1-C8), mono (phenyl or naphthyl) ureidoalkyl (C1-C8), mono (phenyl or naphthyl) alkyl (C1-C8) ureidoalkyl (C1-C8), monohaloalkyl (C1-C8) ureidoalkyl (C1-C8), (haloalkyl) (C 1 -C 8)) (C 1 -C 8 alkyl) ureido (C 1 -C 8) alkyl, (C 1 -C 8) alkoxy (C 1 -C 8) carbonyl) ureido (C 1 -C 8) alkyl, glycinamide, mono (C 1 -C) alkyl 8) glycolate, aminocarbonylglycinamido, (C1-C8 alkoxy) (C1-C8) alkylcarbonyl) glycinamide, (aminocarbonyl) (C1-C8 alkyl) glycinamide, (C1-C8 alkoxy) carbonylalkyl (C1- C8) carbonyl) (C 1 -C 8 alkyl) glycinamide, (C 1 -C 8 alkoxy) carbonylamino (C 1 -C 8) alkylcarbonyl) glycinamide, (phenyl or naphthyl) carbonylglycinamide, ((phenyl or naphthyl) carbonyl) (C 1 -C 8 alkyl) C8)) glycinamide, (mono (phenyl or naphthyl) alkyl (C1-C8) aminocarbonyl) glycinamide, (mono (phenyl or naphthyl) -alkyl (C1-C8) aminocarbonyl) (C1-C8 alkyl) glycinamide, (mono (phenyl or naphthyl) aminocarbonyl) glycinamide, (mono (phenyl or naphthyl) aminocarbonyl) (C 1 -C 8 alkyl) glycinamide, glycinamide (C 1 -C 8) alkyl, alaninamide, (C 1 -C 8) monoalkyl alaninamide, alaninamido (C 1 -C 8) alkyl ), 3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur) alkyl (C1-C8) , -. . or R3 is a heterocyclic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, (C1-C8) alkyl, (C1-C8) alkyl, suphonyl, - (phenyl or naphthyl) sulfonyl, (C 1 -C 8) alkoxy, (C 1 -C 8) hydroxyalkoxy, (C 1 -C 8) haloalkyl, formyl, nitro, cyano, (C 1 -C 8) haloalkoxy, (C 2 -C 8) alkenyl, (C 2 -C 8) alkynyl, phenyl or naphthyl, (phenyl or naphthyl) (C1-C8) alkyl, amino, (C1-C8) aminoalkyl, (C1-C8) dialkylamino, mono (phenyl or naphthyl) amino, mono (phenyl or naphthyl) alkyl (C1- C8) amino, (C1-C8) alkylcarbonylamino, (C1-C8) alkoxycarbonylamino, (C2-C8) alkenylcarbonylamino, (C3-C0-cycloalkyl) carbonylamino, (phenyl or naphthyl) carbonylamino, (C1-C8) haloalkylcarbonylamino , to the coxi (C 1 -C 8) alkyl (C 1 -C 8) carbonylamino, alkoxy (C 1 -C 8) carbonylalkyl (C 1 -C 8) carbonylamino, (C 1 -C 8 alkyl) carbonyl) (C 1 -C 8 alkyl) amino , (C 1 -C 8) alkoxycarbonyl) (C 1 -C 8 alkyl) amino, (C 1 -C 8) alkyl sulfonylates no, (C 1 -C 8) aminoalkyl, (C 1 -C 8) aminoalkyl (C 1 -C 8) alkyl, (C 1 -C 8) dialkyl amino (C 1 -C 8) alkyl, (C 1 -C 8) alkylcarbonylamino (C 1 -C 8) alkyl, (phenyl) or naphthyl) carbonylamino (C 1 -C 8) alkyl, (C 1 -C 8 alkyl) carbonyl) (C 1 -C 8 alkyl) amino (C 1 -C 8) alkyl, (C 1 -C 8) alkoxy carbonylamino (C 1 -C 8) alkyl, carboxy, alkoxy (C1-C8) carbonyl, (phenyl or naphthyl) (C1-C8) alkoxycarbonyl, (C1-C8) alkylcarbonyl, (phenyl or naphthyl) carbonyl, (phenyl or naphthyl) alkyl (C1-C8) carbonyl, aminocarbonyl, (C 1 -C 8) monoalkyl aminocarbonyl, (C 1 -C 8) dialkyl aminocarbonyl, mono (phenyl or naphthyl) aminocarbonyl, aminocarbonylalkyl (C 1 -C 8), (C 1 -C 8) monoalkyl aminocarbonylalkyl (C 1 -C 8), dialkyl (C 1 -C 8) aminocarbonylalkyl (C1-C8), mono (phenyl or naphthyl) aminocarbonylalkyl (C1-C8), guanidino, ureido, monoalkyl (Cl-C8) ureido, ureidoalkyl (C1-C8), monoalkyl (C1-C8) ureidoalkyl (C1-C8) ), and glycinamide; RESUMF DERIVATIVES OF PIPERAZINE AND ITS USE AS ANTI-INFLAMMATORY AGENTS This invention is directed to the acyl piperazine derivatives which are useful as anti-inflammatory agents. This invention is also directed to pharmaceutical compositions containing the compounds of the invention, and methods of using the components for the treatment of inflammatory problems in humans.