SIGMA RECEPTOR LIGANDS AND THE USE THEREOF

Abstract: The invention relates to methods for the treatment of schizophrenia or other psychoses by administering a pharmaceutical composition comprising an effective amount of certain sigma receptor ligands to a patient in need of such treatment. The invention further relates to novel sigma receptor ligands having high binding to the sigma receptor and pharmaceutical compositions thereof.

Description: TITLE OF THE INVENTION SIGMA RECEPTOR LIGANDS AND THE USE THEREOF FIELD OF THE INVENTION The invention is in the field of medicinal chemistry. In particular, the invention relates to new compounds having high binding to the sigma receptor and pharmaceutical compositions thereof. These sigma receptor ligands are useful for the treatment of schizophrenia and other psychoses. BACKGROUND OF THE INVENTION Brain σ receptors are the subject of intense investigation in light of the fact that σ receptors bind many psychotropic drugs (Sonders et al .. Trends Neurosci. 11:37-40 (1988)). Moreover, certain σ receptor ligands have antipsychotic activity which suggests that sigma receptor active compounds may be used for the treatment of schizophrenia (Largent et al .. Eur. J. Pharmacol. 11:345-347 (1988). Certain neuroleptic (i.e. antipsychotic) agents bind with very high affinity at σ sites. Su, T., J. Pharmacol. Exp Ther. 223:284 (1982); Tarn, S.W., Proc. Nat. Acad. Sci (USA) 80:6703 (1983). One agent with very high affinity for σ sites (Ki c_a 1 nM; i.e., approximately 100-fold higher affinity than N-allyl normetrazocine (NANM)) is the neuroleptic agent haloperidol. Tarn, S.W. et al .. Proc. Nat. Acad. Sci (USA) 81:5618 (1984). σ- opiates, such as NANM, bind with low affinity at typical opiate receptors but bind with significant affinity at PCP receptors. Current neuroleptic agents are thought to produce their effects via a dopaminergic (DA) mechanism; they display very high affinities for DA binding sites. However, not all of the potent neuroleptic agents bind at [ 3 H]NANM-labelled σ sites, nor do the σ-opiates bind at DA sites. This has led to the suggestion that the sites labelled by [ 3 H]NANM be termed σ-sites and not σ-opiate sites (i.e., it may simply be coincidental that the σ opiates possess an opiate-like chemical structure). In addition, there has been speculation that agents with high affinity for σ sites may either (a) produce psychotic effects (if they behave as agonists), or (b) produce antipsychotic effects (if they behave as antagonists). It has further been speculated that certain neuroleptic agents, such as haloperidol, produce their antipsychotic effects by both a σ and DA mechanism. Tarn, S.W. and Cook, L., Proc. Nat. Acad. Sci. (USA) 81:5618 (1984). In fact, [ 3 H]haloperidol, in combination with spiperone (an agent with high affinity for DA sites and essentially no affinity for σ sites) is now commonly used to label σ sites in radioligand binding studies. A number of researchers have studied the structure-activity relationship of σligands. For example, Manallack, D.T. et al . , Eur. J. Pharmacol. 144:231-235 (1987), disclose a receptor model for the phencyclidine and σ binding sites. Manallack et al . disclose that in a recent SAR study (Largent et al ., in press), σ site affinity was shown to be enhanced by large N-alkyl substituents, e.g., benzyl or phenethyl. Largent, B.L. et al., Mol. Pharmacol. 32:772-784 (1987), disclose a study of the structural determinants of sigma receptor affinity. In particular, Largent et al . teach that several piperidine and piperazine derivatives have sigma receptor activity. Largent et al . also disclose that affinity for the sigma receptor is markedly influenced by the N-alkyl substituents, with more lipophilic substituents affording greater affinity for the sigma receptor binding sites. Sharkey, J. et al., Eur. J. Pharmacol. 149:171-174 (1988), studied the σ receptor binding activity of cocaine-related compounds. There has been considerable research on amphetamine and amphetamine derivatives. For example, Aldous, F.A.B., J. Med. Chem. 17:1100-1111 (1974), discloses a structure-activity study of psychotomimetic phenylalkylamines. Aldous et al . also disclose a number of halo, methyl, and methoxy substituted amphetamines. Fuller, R.W. et al., J. Med. Chem. 14:322-325 (1971), disclose amphetamine derivatives substituted on the 3- and 4- positions of the aromatic ring with one or more chloro, fluoro, alkyl, phenoxy, alkoxy and hydroxy substituents. Foye, W.O. et al., J. Phar . Sci. 68:591-595 (1979), disclose heterocyclic analogues of amphetamine having 2-furyl, 2- thienyl, 3-methyl-2-phenol, 3-pyridyl, 6-methyl-2-pyridyl, 4- chlorophenyl, and 1-naphthyl rings. Boissier, J.R. et al. , Chem. Abstr. 66:46195h (1967), disclose N-benzyl amphetamine derivatives of the Formula (I): wherein X is methyl, CF 3 , methoxy, or a halogen and R is hydrogen or methyl. These compounds reportedly have anoretic activity and low toxicity. Particular compounds disclosed by Boissier et al . include N-(l-phenyl-2-propyl)-4-chlorobenzylamine, N-(l-phenyl-2- propyl)-4-methylbenzyl-amine, and N-(l-phenyl-2-propyl)-4- methoxybenzylamine. Boissier, J.R. et al., Chem. Abstr. 67:21527a (1967), disclose amphetamine derivatives of the Formula (II): CH, R 1 wherein R 1 is hydrogen, 4-Cl, 3-Cl , or 3-CF 3 and R 2 is 2- chlorophenyl, 4-chlorophenyl, 4-bromophenyl, 3-CF 3 -phenyl, 4- tolyl, 4-methoxyphenyl , phenyl, 2-furyl, 2-tetrahydrofuryl , 2- thienyl, or 3-thienyl. Reportedly, these compounds were tested for anorexi genie activity in rats and dogs. Osbond, J.M. et al . , Chem. Abstr. 69:51816c (1968), disclose N,N-bis-(omega-phenylalkyl)amines having the Formula (HI): R 1 R R R 1 wherein R 1 , R 2 , and R 3 are hydrogen, chloro, CF 3 , or methoxy. Gosztonyi, T. et al . , J. Label. Comp. Radiopharm.8:293-303 (1977), disclose the preparation of N-substituted omega-haloalkyl derivatives of p_-chloro amphetamine. Also disclosed, is the corresponding omega- hydroxy alkyl amine. Coutts, R.T. et al.. Can. J. Microbiol.26:844-848 (1980), disclose N-substituted rj-chloro amphetamines having the following Formula (IV): wherein R 1 is 2-butanone-3-yl , 2-hydroxybutane-3-yl , 1- hydroxybutane-3-yl , or acetate. Fuller, R.W. et al ., J. Pharm. Pharmacol. 25:828-829 (1973), disclose lipid-soluble derivatives of amphetamine comprising 2-chloro, 3-chloro, 4-chloro, and beta, beta-difluoro- ampheta ine, and the effect thereof on amphetamine levels in the brain. Fuller, R.W. et a . , Neuropharmacology 14:739-746 (1975), disclose 4-chloroamphetamine, 4-bromoamphetamine, and 4- fluoroampheta ine and the effect thereof on serotonin metabolism. Conde, S. et al . , J. Med. Chem.21:978-981 (1978), disclose thiophene analogues of chloroamphetamine having the following Formula (V): wherein X, Y, and Z are chloro or hydrogen, and the effect thereof on serotonin levels in the brain. Lukovits, I., Int. J. Quantum. Chem. 20:429-438 (1981), discloses various halo, methyl, and methoxy ring-substituted amphetamines, and the inhibitory potencies thereof on phenyl ethanol ami ne-N-methyl transferase. Law, B., J. Chromatoq. 407:1-18 (1987), discloses amphetamine analogues comprising 1-methyl -2-(2' - naphthyl) ethyl amine, N-isopropyl-2-(2'-naphthyl)ethylamine, and N-i sopropyl -2-phenyl ethyl amine . Johansson, A.M. et al., J. Med. Chem. 30:602-611 (1987), disclose N-substituted 2-aminotetralins of the Formula (VI): wherein R 1 is OH or OMe and R 2 and R 3 are H or CτC 4 lower alkyl. These compounds were tested for dopamine receptor agonist and antagonist activities. Hacksell, U. et al., J. Med. Chem. 22:1469-1475 (1979), disclose N-alkylated-2-aminotetralins of the Formula (VII): wherein R 1 is OH or OMe, R 2 is lower alkyl, and R 3 is lower alkyl or phenethyl . In particular, Hacksell et al . disclose two aminotetral ns of the Formulae (VIII) and (IX): (VIII) (IX) These compounds reportedly have dopamine-receptor stimulating activity. McDermed, J.D. et al.. J. Med. Chem. 18:362-367 (1975), disclose N-alkyl aminotetralins of the Formula (X): wherein R 1 and R 2 is one of a large number or alkyl, heteroalkyl, and alkaryl groups. In particular, McDermed et al . disclose two compounds of the Formula (XI) and (XII): (XI) (XII) These compounds are reportedly dopamine receptor agonists. Glennon, R.A. et al., Pharmacol. Biochem. Behav.21:895-901 (1984), disclose that 2-aminotetralin is a conformationally restricted analog of amphetamine which is about one-half as effective as racemic amphetamine. Beaulieu, M. et al., Eur. J. Pharmacol. 105:15-21 (1984), disclose N,N-disubstituted 2-aminotetralins of the Formula (XIII) These compounds are reportedly potent D-2 dopamine receptor agonists. Naiman, N. et al., J. Med. Chem. 32 :253-256 (1989), disclose 2-(alkylamino)tetralin derivatives ofthe Formula (XIV): wherein R is H, OMe, or OBz; R 1 is H, Me, or n-Pr; and R 2 is H, n-propyl, benzyl, phenethyl, or phenpropyl. These compounds reportedly bind to the 5-HT 1A receptor site. Beecroft, R.A. et al.. Tetrahedron 41:3853-3865 (1985), disclose N,N-disubstituted piperazines having the Formulae (XV)- (XVIII): (xv > (XVI) l l -Kp ( CH 2 ) 2 N ..r χ ^.KCH 2 CH 2 /~\ . * 0 (XVII) v_/ Fuller, R. . et al . , J. Pharmacol. Exp. Therapeut. 218:636- 641 (1981), disclose substituted piperazines having the following Formulae (XIX) and (XX): (XIX) (XX) which reportedly act as serotonin agonists and inhibit serotonin uptake or serotonin oxidation. Fuller, R.W. et al ., Res. Co rnun. Chem. Pathol . Pharmacol. 29:201-204 (1980), disclose the comparative effects on 5- hydroxyindole concentration in rat brain by p_-chloroamphetamine and l-(p_-chlorophenol)piperazine having the following Formulae (XXI) and (XXII): (XXI) (XXII) Boi ssier, J. et al . , Chem. Abstr. 61: 10691c, di scl ose di substi tuted piperazi nes having the Formul a (XXII I) : R^-X-N N-R 2 (XXI II) wherein R 1 and R 2 are aryl and X is a straight or branched chain alkylene of 0,-0 3 . The compounds are reportedly adrenolytics, hypotensors, potentiators of barbiturates, and depressants of the central nervous system. Roessler, Chem Abstr. 6_l:13328g, disclose piperazine derivatives of the Formula (XXIV): wherein R = H or methoxy and R 1 = H, o-ethylphenyl, or p_- chlorophenyl . Ruschig, H et al . , Chem. Abstr. 53:3253e, disclose a large series of N,N-disubstituted piperazines including l-benzyl-4-(3- chloro-4-methylphenyl)piperazine. Shvedov, V.I. et al ., Chem. Abstr. 73:11806q (1970), disclose 4-(R 2 CH 2 -CH 2 substituted)-l-phenyl-piperazines wherein R 2 is phenyl, 2-naphthyloxy, 3-indolyl, 2-methyl-3-indolyl or 2- benzimidazolyl . Popov, D., Chem. Abstr. 67:54102m (1967), disclose disubstituted piperazines of the Formula (XXV): wherein R is tolyl, rj-methoxyphenyl , m-ethoxyphenyl, beta- naphthyl, m-or p . - carboxy! phenyl, 3,4-dimethoxyphenyl, 5- hydrindenyl, fi-chloro-phenyl, p_-bromophenyl , p_-iodophenyl, 3,4- dichlorophenyl, and m- or p_-nitrophenyl . Glennon, R.A et al., J. Med. Chem. 31:1968-1971 (1988), disclose various N,N-disubstituted piperazines having the Formulae (XXVI) -(XXIX): (XXVII) (XXVIII) These compounds reportedly have high affinity for the 5-HT 1A serotonin binding site. Prasad, R.N et al., J. Med. Chem. 11:1144-1150 (1968), disclose N,N-disubstituted piperazines of the Formula (XXX): wherein R 1 is phenyl or o-methoxyphenyl and R 2 is 2,4- dichlorophenyl, o-, m- or p.- methoxyphenyl, 3,4-dimethoxyphenyl, or m-tolyl. These compounds are reported to be antihypertensive agents. SUMMARY OF THE INVENTION The invention relates to the discovery that certain phenylalkyl-amine, aminotetralin, piperazine, piperidine and related derivatives have high binding to the sigma receptor and, unexpectedly, low binding for the PCP and DA receptors. Thus, the sigma receptor ligands of the present invention can be used for the treatment of schizophrenia without the side effects of traditional neuroleptic agents which also bind to the DA receptor. In particular, the invention relates to methods of treating a human being suffering from schizophrenia or other psychoses, which comprises administering to said human a therapeutically effective amount of a compound selected from the Formulae (XXXI) and (XXXII): (XXXII) wherein said compound exhibits high binding activity with respect to the sigma receptor. The invention also relates to certain novel sigma receptor ligands defined by Formulae (XXXI) and (XXXII) as well as pharmaceutical compositions comprising these novel sigma receptor ligands. Surprisingly, the present inventor has discovered that certain N-substituted phenylalkylamines, although seemingly related to amphetamine, have activities which are, in fact, very much unlike amphetamine. Instead, the N-substituted phenylalkylamines have high affinity to the sigma receptor and low affinity to the DA and PCP receptors DESCRIPTION OF THE PREFERRED EMBODIMENTS The invention relates to a method of treating a human being suffering from schizophrenia and other psychoses, which comprises administering to said human a therapeutically effective amount of a compound having the Formula (XXXI): wherein: Ar is aryl or heteroaryl wherein aryl or heteroaryl can be substituted by hydrogen, halogen such as chloro, fluoro, bromo, iodo, CF 3 , C^Ce alkoxy, C 2 -C β dialkoxymethyl , C^Ce alkyl, cyano, C 3 -C 15 dialkylaminoalkyl, carboxy, carboxamido, haloalkyl, C^C β haloalkylthio, ally!, aralkyl, C 3 -C β cycloalkyl, aroyl, aralkoxy, C 2 -C 6 acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, an aryl ring fused to a substituted benzene ring, a substituted aryl ring fused to a benzene ring, a heteroaryl ring fused to a benzene ring, a substituted heteroaryl ring fused to a benzene ring, C 3 -C β heterocycloalkyl, a C 3 -C β heterocycloalkyl ring fused to a benzene ring, alkylthio, C,-C 6 alkylsulfonyl, alkylsulfinyl, C,-C 6 haloalkylsulfinyl, arylthio, C.,-C 6 haloalkoxy, amino, C,-C 6 alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, N- alkylcarbamoyl , C 2 -C 15 N,N-dialkylcarbamoyl , nitro and C 2 -C 15 dial- kylsulfamoyl ; R is hydrogen or alkyl; R 1 is independently selected from the group consisting of hydrogen, 0,-Ce alkyl, hydroxy, amino, C,-C 6 alkylamino or =0 (a double bonded oxygen); or R and R 1 together form a morpholino ring; n is 0-5; W is -(CH 2 ) P - or -H H-, wherein p is 1-3; X is -(CH 2 ) q -, wherein q is 1-6; -(CH 2 ) r -C≡C-(CH 2 ) r -, wherein each r is 0-3 independently; -(CH 2 ) r -CH=CH-(CH 2 ) r -; 0 // -(CH 2 ) r -C-(CH 2 ) r -; -(CH 2 ) r -Y-(CH 2 ) r -, wherein Y is 0 or S; or alkyl (wherein Z is hydrogen); Z is aryl, heteroaryl or cycloalkyl, wherein aryl, heteroaryl and cycloalkyl can be substituted by hydrogen, halogen such as chloro, fluoro, bromo, iodo; CF 3 , C t -C β alkoxy, C 2 -C 6 dialkoxy- methyl, C τ -C 6 alkyl, cyano, C 3 -C 15 dial kyl anrinoal kyl, carboxy, carboxamido, C,-C β haloalkyl, C^- β haloalkyl thio, ally!, aralkyl, C 3 -C β cycloalkyl, aroy , aralkoxy, C 2 -C β carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C β heterocycloalkyl, C-,-C 6 alkylthio, C n -C β al yl sul f onyl , C^Ce haloalkylsulfonyl, C-,-C β alkyl sulfinyl, C,-C 6 haloalkyl sulfinyl, arylthio, C,-C β haloalkoxy, amino, C,-C 6 alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, C,-C β N-al kyl carbamoyl, C 2 -C 15 N,N-di alkyl carbamoyl, nitro or C 2 -C 15 di alkyl sul famoyl ; wherein said compound exhibits high binding activity with respect to the sigma receptor. The invention also relates to methods of treating schizophrenia and other psychoses using compounds having the Formula (XXXIII): R 1 R I I Ar — (CH) n -N-X-Z (XXXIII) wherein Ar, n, R, and R 1 , X and Z are defined above; wherein said compound exhibits high binding activity with respect to the sigma receptor. Especially preferred compounds within the scope of Formula (XXXIII) include N-phenethyl-1 -phenyl -isopropyl amine, N- phenyl propyl -1-phenylisopropyl amine, N-(2-phenoxyethyl)-l- phenyl isopropyl amine, N- (3-phenyl -3 -propanon-1-yl ) -1- phenyl i sopropyl ami ne , N- (4-phenyl butyl ) - 1 -phenyl i sopropyl ami ne , N- (3- (1-naphthyl) propyl) -1-phenylisopropyl amine, N-(3-(2- naphthyl) propyl) -1-phenylisopropyl amine, N- (3-phenyl -2-propyn-l- yl) -1-phenylisopropyl amine, N- (3-phenyl propyl )-3-(4- hydroxyphenyl ) isopropyl amine, N- (3-phenyl propyl )-3-(4- ethox phenyl ) isopropyl amine, N- (3-phenyl propyl )-3-(3- bromophenyl ) isopropyl am ne, N- (3-phenyl propyl )-3-(4- bromophenyl)isopropylamine, N-(3-phenylpropyl )-3-(3,4- dichlorophenyl ) isopropyl amine, N- (3 -phenyl propyl )-3-(4- iodophenyl) isopropyl amine, N- (3-phenyl propyl ) -3- (3- trifluoromethyl -phenyl) isopropyl amine, N-(2-phenethyl)-N-methyl- 1-phenyl isopropyl -amine, N- (3-phenyl propyl )-l-phenyl propan-1-one- 2-amine, N-(2-indane)-3-phenylisopropylamine, N-(2-indane)-3- phenyl propyl amine, N,N-di-( (3-phenyl) propyl) amine, N-(2-(l- naphthyl )ethyl ) -1 -phenyl i sopropyl amine, N- (2- (2-naphthyl ) ethyl ) - 1- phenyl isopropyl amine, N-(2-(l-naphthyl)propyl)-l- phenylisopropylamine, and N-(2-(2-naphthyl)propyl)-l- phenyl isopropyl amine. The invention also relates to methods of treating schizophrenia with compounds related to Formula (XXXII) where W is -(CH 2 ) P - having the Formula (XXXIV): R 1 (XXXIV) wherein Ar, n, p, R, R 1 , X and Z are as defined above; and wherein said compound exhibits high binding activity with respect to the sigma receptor. The invention also relates to methods of treating schizophrenia and other psychoses with compounds of the Formula (XXXII): (XXXII) wherein X and Z are as defined above and V is N or -CM-, wherein M is hydrogen, C,-C 6 alkyl, alkoxy, hydroxy, fluoro, chloro, bromo, trifluoromethyl, or represents one half of a double bond (with the neighboring endocyclic carbon); R 2 is independently selected from the group consisting of hydrogen, chloro, fluoro, bromo, iodo, CF 3 , alkoxy, C 2 -C 6 dialkoxymethyl, alkyl, cyano, C 3 -C 15 dialkylaminoalkyl, carboxy, carboxamido, 0,-C 8 haloalkyl, C,-C β haloalkylthio, ally!, aralkyl, C 3 -C 6 cycloalkyl, aroyl , aralkoxy, C 2 -C β carboxy!ic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, C,-C 6 alkylthio, C,-C β alkylsulfonyl, C,-C β haloalkylsulfonyl, 0,-Cg alkylsulfinyl, haloalkylsulfinyl, arylthio, 0,-0 6 haloalkoxy, amino, alkylamino, dialkylamino, hydroxy, carbamoyl, N-alkylcarbamoyl, C 2 -C 15 N,N- dialklcarbamoyl, nitro and C 2 -C 15 dialkylsulfamoyl ; and wherein said compound exhibits high binding activity with respect to the σ receptor. Preferably, the invention relates to the treatment of schizophrenia and other psychoses with a piperidine derivative having Formula (XXXV): wherein R 2 , X and Z are as defined above. The invention also relates to the treatment of schizophrenia and other psychoses by administering a compound related to those of Formula XXXIII and having the Formula (XXXVI): (XXXVI) wherein a is 1-8; b is 1-8; R is as defined above; wherein said compound exhibits high binding activity with respect to the σ receptor. Preferably, compounds which are useful for the treatment of schizophrenia and which are within the scope of Formula (XXXI) are naphthyl derivatives having Formula (XXXVII): (XXXVII) wherein R, R 2 , a and b, as defined above, may be the same or different; wherein said compound exhibits high binding activity with respect to the σ receptor. Other compounds useful for the treatment, of schizophrenia include morpholino derivatives having Formula (XXXVIII): (XXXVIII) wherein Ar, X and Z are defined above; wherein said compound exhibits high binding activity with respect to the σ receptor. The sigma receptor ligands of the present invention may exist in racemic form or in the optically active stereoisomeric form. Most preferably, the compounds exist in the S-(+) form. The invention also relates to certain novel sigma receptor ligands and pharmaceutical compositions comprising the novel sigma receptor ligands. In particular, the invention relates to compounds having the Formula (XXXI): R 1 wherein Ar n, R, R 1 , W and Z are as defined above and X is -(CH 2 ) q -, wherein q is 3-6; -(CH 2 ) r -C≡C-(CH 2 ) r -, wherein each r is 0-3 independently; -(CH 2 ) r -CH=CH-(CH 2 ) r -; 0 // -(CH 2 ) r -C-(CH 2 ) r -; -(CH 2 ) r -Y-(CH 2 ) r -, wherein Y is 0 or S; or alkyl (wherein Z is hydrogen); wherein said compound exhibits high binding activity with respect to the σ receptor. Sigma receptor ligands having the above Formula (XXXI) wherein q is 3-6 have unexpectedly high binding to the sigma receptor (see Example 2, below). The invention also relates to sigma receptor ligands having the Formula (XXXIII): R R Ar—(C IH) n -N r-X-Z (XXXIII) wherein n, R, R 1 , Z, and Ar are defined above, and X is -(CH 2 ) q -, wherein q is 3-6; -(CH 2 ) r -C≡C-(CH 2 ) r -, wherein each r is 0-3 independently; -(CH 2 ) r -CH=CH-(CH 2 ) r -; 0 // -(CH 2 ) r -C-(CH 2 ) r -; -(CH 2 ) r -Y-(CH 2 ) r -, wherein Y is 0 or S; or alkyl (wherein Z is hydrogen); wherein said compound exhibits high binding activity with respect to the σ receptor. Sigma receptor ligands having the above Formula (XXXV) wherein q is 3-6 also have unexpectedly high binding to the sigma receptor (see Example 2). The invention also relates to compounds of the Formula (XXXII): (XXXII) wherein R 2 , V and Z are as defined above; X is -(CH 2 ) r -C≡C-(CH 2 ) r -, wherein r is 0-3; -(CH 2 ) r -CH=CH-(CH 2 ) r -; 0 // -(CH 2 ) r -C-(CH 2 ) r -; -(CH 2 ) r -Y-(CH 2 ) r -, wherein Y is 0 or S; or C,-C β alkyl (wherein Z is hydrogen); wherein said compound exhibits high binding activity with respect to the σ receptor. Sigma receptor ligands having the above Formula (XXXII) wherein q is 3-6 also have unexpectedly high binding to the sigma receptor (see Example 2). The invention also relates to compounds of the Formula (XXXV) : wherein R 2 and Z are as defined above; X is -(CH 2 ) r -C≡C-(CH 2 ) r -, wherein each r is 0-3 independently; -(CH 2 ) r -CH=CH-(CH 2 ) r -; 0 // -(CH 2 ) r -C-(CH 2 ) r -; -(CH 2 ) r -Y-(CH 2 ) r -, wherein Y is 0 or S; or C,-C 6 alkyl (wherein Z is hydrogen); wherein said compound exhibits high binding activity with respect to the σ receptor. Sigma receptor ligands having the above Formula (XXXV) also have unexpectedly high binding to the sigma receptor (see Example 2). The invention also relates to compounds which are related to the Formula XXXII and having the Formula (XXXIX): (XXXIX) wherein R 2 , M, X and Z are as defined above; U is selected from the group consisting of hydrogen, halogen such as chloro, fluoro, bromo, iodo; CF 3 , C,-C β alkoxy, C 2 -C β dialkoxy- methyl, C,-C 6 alkyl, cyano, C 3 -C 15 dial kyl ami noal kyl, carboxy, carboxamido, 0,-C 8 haloalkyl, 0,-Cg haloalkyl thio, allyl, aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C β acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, an aryl ring fused to a substituted benzene ring, a substituted aryl ring fused to a benzene ring, a heteroaryl ring fused to a benzene ring, a substituted heteroaryl ring fused to a benzene ring, C 3 -C 6 heterocycloalkyl, a C 3 -C β heterocycloalkyl ring fused to a benzene ring, C--C 6 alkylthio, C,-C 6 alkyl sul fonyl, 0,-Cg haloalkyl- sulfonyl, alky 1 sul finyl, C,-C 6 haloalkyl sulfinyl, arylthio, 0,-Cg haloalkoxy, amino, 0,-Cg alkylamino, C 2 -C 15 dial kyl amino, hydroxy, carbamoyl, C,-C β N-al kyl carbamoyl, C 2 -C 15 N,N-dialkyl- carbamoyl, nitro and C 2 -C 15 di alkyl sul famoyl; wherein said compound exhibits high binding activity with respect to the σ receptor. The invention also relates to a compound of the Formula (XXXVI): (CH 2 ) a -NH- (XXXVI) wherein a is 1-8; b is 1-8; R is hydrogen or C|-C 6 alkyl; R 2 is independently selected from the group consisting of hydrogen, chloro, fluoro, bromo, iodo, CF 3 , 0,-Cg alkoxy, C 2 -C 6 dialkoxymethyl, C,-C 6 alkyl, cyano, C 3 -C 15 dial kyl ami noal kyl, carboxy, carboxamido, C.-Cg haloalkyl, haloalkylthio, allyl, aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C β carboxy! ic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, C^Cg alkylthio, C,-C β alkyl sul fonyl, C-,-Cg hal oal kyl sul fonyl , alkyl sulfinyl, C-,-C β haloalkyl sulfinyl , arylthio, C,-C 6 haloalkoxy, amino, C,-C 6 alkyl -ami no, dialkylamino, hydroxy, carbamoyl, C,-C 6 N- alkyl carbamoyl, C 2 -C 15 N, N-dialkl carbamoyl , nitro and C 2 -C 15 di alkyl sul famoyl ; wherein said compound exhibits high binding activity with respect to the σ receptor. The invention also relates to naphthyl derivatives within the scope of Formula (XXXI) having Formula (XXXVII): (XXXVII) wherein R, R , a and b, as defined above, may be the same or different; wherein said compound exhibits high binding activity with respect to the σ receptor. The invention also relates to orpholino derivatives having Formula (XXXVIII): CH 2 / \ 0 CH 2 Ar-CH-CH,-N-X-Z (XXXVIII) wherein Ar, X and Z are defined above; wherein said compound exhibits high binding activity with respect to the σ receptor. Also as derivatives of compound XXXIII, this invention is concerned with a compound having the Formula (LII) R 1 R I Cy- (CH)„-N-X-Z (LII) wherein Cy is C 3 -C 8 cycloalkyl and Ar, R 1 , n, R, X, and Z are defined as above. Compounds derived from the Formula XXXII are also an aspect of the present invention. These compounds include a compound of the Formula (LIII) wherein X 1 is -(CH 2 ) r -C≡C-(CH 2 ) r -, wherein each r is 0-3 independently; -(CH 2 ) r -CH=CH-(CH 2 ) r -; -(CH 2 ) r -Y-(CH 2 ) r -, wherein Y is 0 or S; or C,-C β alkyl (wherein Z is hydrogen); and R 2 , V, X, and Z are defined as above. Typical C,-C β alkyl groups include methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, i-butyl, pentyl and hexyl groups. Typical C 2 -C 6 carboxylic acyl groups include acetyl, propanoyl, i-propanoyl, butanoyl, s-butanoyl, pentanoyl and hexanoyl groups. Typical aryl groups include phenyl, naphthyl, phenanthryl, and anthracyl groups. Typical C-,-C β alkoxycarbonyl groups include carbonyl substituted by methoxy, ethoxy, propanoxy, i-propanoxy, n- butanoxy, t-butanoxy, i-butanoxy, pentanoxy, and hexanoxy groups. Typical aralkyl groups include the above-listed C,-C β alkyl groups substituted by phenyl, naphthyl , phenanthryl , and anthracyl groups. Typical C 2 -C β alkenyl groups include vinyl, allyl, 2- butenyl, 2-pentenyl, and 2-hexenyl groups. Typical C 2 -C 6 alkynyl groups include acetynyl and propargyl groups. Typical halo groups include fluorine, chlorine, bromine and iodine. Typical aroyl groups include carbonyl substituted by phenyl, naphthyl, phenanthryl, and anthracyl groups. Typical aralkanoyl groups include carbonyl substituted by the above-listed aralkyl groups. Typical aralkoxy groups include the above listed alkoxy groups substituted by phenyl, naphthyl, phenanthyl, and anthracyl groups. Typical substituted aryl groups include the above-listed aryl groups substituted by halo, hydroxy, amino, and the like. Typical heteroaryl groups include furyl, thienyl, pyrrolyl, thiazolyl, pyridyl, pyrimidinyl, py izinyl, oxazolyl and phthalimido groups which may be fused to a benzene ring. Typical substituted heteroaryl groups include the above- listed heteroaryl groups substituted by halo, C,-C 6 alkyl and the like. Typical C 5 -C β heterocycloalkyl groups include tetrahydrofuranyl , tetrahydropyranyl, piperidinyl, piperazinyl, morpholino and pyrrolidinyl groups. Under the binding activity studies, an IC 50 value of at most about 100 nM, preferably at most about 25 nM, more preferably at most 10 nM, most preferably at most 1 nM indicates a high binding affinity. In the present application, the term "high affinity" is intended to mean a compound which exhibits an IC 50 of less than 100 nM in a sigma receptor binding assay, preferably against 3 H- DTG as disclosed by Weber et al . , Proc. Natl. -Acad. Sci (USA) 83:8784-8788 (1986). Especially preferred sigma ligands exhibit IC 50 values of less than about 25 nM, more preferably less than about 10 nM, most preferably less than about 1 nM. Surprisingly, the inventor has discovered that the sigma receptor ligands of the present invention exhibit low affinity to the DA and PCP receptors. Thus, the sigma receptor ligands of the present invention may be used for the treatment of schizophrenia without the untoward side effects associated with binding at the DA receptor. By the term "low affinity" is intended a binding affinity of >100 nM, more preferably, >1000 nM in a DA or PCP binding assay. Especially preferred sigma receptor ligands have high binding to the sigma receptor and low binding to the DA and/or PCP receptors, as defined herein. By the term "schizophrenia" is intended to include any of a group of severe emotional disorders, usually of psychotic proportions, characterized by misinterpretation and retreat from reality, delusions,, hallucinations, ambivalence, inappropriate affect, and withdrawn, bizarre, or regressive behavior. See Dorland's Illustrated Medical Dictionary. 26th edition, W.B. Saunders Company, Philadelphia, Pa., pp. 1171 (1981) As discussed above, the sigma receptor ligands of the present invention are highly selective for the sigma receptor and show low affinity for the DA and PCP receptors. Thus, in addition to the treatment of schizophrenia, the sigma selective ligands of the present invention may also be used as a pharmacological tool in an animal model for the screening of potential sigma receptor agents. The sigma receptor ligands of the present invention may also be radiolabelled with, for example, 3 H, 14 C, 125 I and 131 I. In their radiolabelled form, the sigma receptor ligands of the present invention may be used for audoradiography studies of the sigma receptor sites in neuronal tissue. The σ receptor ligands of the present invention may be prepared by general methods of synthesis as disclosed in Example 1. For example, a σ receptor ligand having Formula (XXXX) may be prepared by reductive amination of a compound having Formula (XXXXI) with an aldehyde having Formula (XXXXII) according to Scheme I outlined below. Scheme I R 1 (XXXXII) (X [H] R 1 (XXXX) The starting compound having Formula (XXXXI), where W = -H H-, may be prepared by general methods of organic synthesis. For general methods of preparing compounds of Formula (XXXXI), reference is made to Fuller, R.W. et al ., J. Med. Chem. 14:322- 325 (1971); Foye, W.O. et al.. J. Pharm. Sci 68:591-595 (1979); Bossier, J.R. et al.. Chem. Abstr. 66:46195h and 67:21527a (1967); Aldous, F.A.B., J. Med. Chem. 17:1100-1111 (1974); Fuller, R.W. et al., J.Pharm. Pharmacol. 25:828-829 (1973); Fuller, R.W. et al ., Neuropharmacoloqy 14:739-746 (1975); Conde, S. et al .. J. Med. Chem. 21:978-981 (1978); Lukovits, I. et al ., Int. J. Quantum Chem. 20:429-438 (1981); and Law, B., J. Chromatoq. 407:1-18 (1987), the disclosures of which are incorporated by reference herein in their entirety. The radiolabelled derivatives having Formula (XXXX) may be prepared by, for example, using a tritiated reducing agent to perform the reductive amination or by utilizing a u C-labelled starting material . Alternatively, where R is H, an N-substituted carboxamide of Formula (XXXXIII) may be reduced, for example, with LiAlH 4 to give the N,N-disubstituted sigma receptor ligand having the Formula (XXXX), below (see- Scheme II). Scheme II R 1 (XXXXIII) LiAlH, R 1 (XXXX) Alternatively, where the starting compound comprises a carbonyl group, the compound having the Formula (XXXXIV) may be reduced with, for example, A1H 3 , diborane: ethyl sulfide or other standard carbonyl reducing reagent to give the σ receptor ligand having Formula (XXXX) according to Scheme III. Sche e III R 1 R 1 The σ receptor ligands having Formula (XXXI) may be prepared by nucleophilic displacement of an electrophile (E) by the amino derivative (XXXXV) as outlined in Scheme IV. Examples of electrophiles which may be used for this purpose include halides such as Cl, Br, or I, tosylate or mesylate. Scheme IV (XXXXV) R 1 Morpholino derivatives having the Formula (XXXXVI) may be prepared by reduction of a compound of the Formula (XXXXVII) with, for example, sodium borohydride to give the ring-closed morpholino derivative (XXXXVI) according to Scheme V. Scheme V R 1 (XXXXVII) (XXXXVI) Alternatively, where the σ receptor ligand comprises a tetrahydropyridine ring (Formula (XXXXVIII)), the tetrahydropyridine ring may be constructed by reaction of a 2- arylpropene derivative (Formula (XXXXIX)) with an alkyl amine (Formula (L)) and para-formaldehyde in the presence of orthophosphoric acid (Scheme VI). Scheme VI -X-Z (XXXXIX) (L) (XXXXVIII) Reduction of the double bond of the compound having Formula (XXXXVIII) with, for example, hydrogen and a hydrogenation catalyst such as Pd/C or Pt gives the corresponding piperidine having Formula (LI): Scheme VII IH1 (XXXXVIII) (LI) Also included within the scope of the present invention are the optical isomers of the compounds of the invention. The optical isomers may be separated by classical resolution techniques by, for example, formation of a salt of the amino group with an optically active acid. A particularly preferred acid for this purpose is (+)-di-p_-toluoyl-D-tartaric acid. The resulting diastereoisomeric salt may then be separated by crystallization, chromatography, or by taking advantage of the differing solubilities of the two diastereoisomeric salts. The free base may then be isolated by treatment with a base such as aqueous ammonia and extraction with an organic solvent. Alternatively, the optical isomers may be prepared by resolution of the starting amine used to prepare the sigma ligand. Also included within the scope of the present invention are the non-toxic pharmaceutically acceptable salts of the compounds of the invention. Acid addition salts are formed by mixing a solution of the sigma ligand of the invention with a solution of a pharmaceutically acceptable non-toxic acid such as hydrochloric acid, fumaric acid, maleic acid, succinic acid, acetic acid, citric acid, tartaric acid, carbonic acid, phosphoric acid, oxalic acid, and the like. In the method of treatment of the present invention, the pharmaceutical compositions may comprise the sigma receptor ligand at a unit dose level of about 0.01 to about 500 mg/kg of body weight, or an equivalent amount of the pharmaceutically acceptable salt thereof, on a regimen of 1-4 times per day. Of course, it is understood that the exact treatment level will depend upon the case history of the animal, e.g., human being, that is treated. The precise treatment level can be determined by one of ordinary skill in the art without undue experimentation. The pharmaceutical compositions of the invention may be administered to any animal which may experience the beneficial effects of the compounds of the invention. Foremost among such animals are humans, although the invention is not intended to be so limited. The pharmaceutical compositions of the present invention may be administered by any means that achieve their intended purpose. For example, administration may be by parenteral , subcutaneous, intravenous, intramuscular, intraperitoneal, transdermal, or buccal routes. Alternatively, or concurrently, administration may be by the oral route. The dosage administered will be dependent upon the age, health, and weight of the recipient, kind of concurrent treatment, if any, frequency of treatment, and the nature of the effect desired. In addition to the sigma receptor ligands, the new pharmaceutical preparations may contain suitable pharmaceutically acceptable carriers comprising excipients and auxiliaries which facilitate processing of the active compounds into preparations which can be used pharmaceutically. Preferably, the preparations, particularly those preparations which can be administered orally and which can be used for the preferred type of administration, such as tablets, dragees, and capsules, and also preparations which can be administered rectally, such as suppositories, as well as suitable solutions for administration by injection or orally, are present at a concentration of from about 0.01 to 99 percent, together with the excipient. The pharmaceutical preparations of the present invention are manufactured in a manner which is itself known, for example, by means of conventional mixing, granulating, dragee-making, dissolving, or lyophilizing processes. Thus, pharmaceutical preparations for oral use can be obtained by combining the sigma ligand with solid excipients, optionally grinding the resulting mixture and processing the mixture of granules, after adding suitable auxiliaries, if desired or necessary, to obtain tablets or dragee cores. Suitable excipients are, in particular, fillers such as saccharides, for example lactose or sucrose, mannitol or sorbitol, cellulose preparations and/or calcium phosphates, for example tricalcium phosphate or calcium hydrogen phosphate, as well as binders such as starch paste, using, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, tragacanth, methyl cellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, and/or polyvinyl pyrrolidone. If desired, disintegrating agents may be added such as the above- mentioned starches and also carboxymethyl-starch, cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof, such as sodium alginate. Auxiliaries are, above all, flow- regulating agents and lubricants, for example, silica, talc, stearic acid or salts thereof, such as magnesium stearate or calcium stearate, and/or polyethylene glycol. Dragee cores are provided with suitable coatings which, if desired, are resistant to gastric juices. For this purpose, concentrated saccharide solutions may be used, which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, polyethylene glycol and/or titanium dioxide, lacquer solutions and suitable organic solvents or solvent mixtures. In order to produce coatings resistant to gastric juices, solutions of suitable cellulose preparations such as acetylcellulose phthalate or hydroxypropymethyl-cellulose phthalate, are used. Dye stuffs or pigments may be added to the tablets or dragee coatings, for example, for identification or in order to characterize combinations of active compound doses. Other pharmaceutical preparations which can be used orally include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer such as glycerol or sorbitol. The push-fit capsules can contain the active compounds in the form of granules which may be mixed with fillers such as lactose, binders such as starches, and/or lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active compounds are preferably dissolved or suspended in suitable liquids, such as fatty oils, or liquid paraffin. In addition, stabilizers may be added. Possible pharmaceutical preparations which can be used rectally include, for example, suppositories, which consist of a combination of one or more of the active compounds with a suppository base. Suitable suppository bases are, for example, natural or synthetic triglycerides, or paraffin hydrocarbons. In addition, it is also possible to use gelatin rectal capsules which consist of a combination of the active compounds with a base. Possible base materials include, for example, liquid triglycerides, polyethylene glycols, or paraffin hydrocarbons. Suitable formulations for parenteral administration include aqueous solutions of the sigma ligands in water-soluble form, for example, water-soluble salts. In addition, suspensions of the active compounds as appropriate oily injection suspensions may be administered. Suitable lipophilic solvents or vehicles include fatty oils, for example, sesame oil, or synthetic fatty acid esters, for example, ethyl oleate or triglycerides. Aqueous injection suspensions may contain substances which increase the viscosity of the suspension include, for example, sodium carboxymethyl cellulose, sorbitol, and/or dextran. Optionally, the suspension may also contain stabilizers. The following examples are illustrative, but not limiting, of the method and compositions of the present invention. Other suitable modifications and adaptations of the sigma receptor ligands as well as the variety of conditions and parameters normally encountered in clinical therapy and which are obvious to those skilled in the art are within the spirit and scope of the invention. EXAMPLES EXAMPLE 1 PREPARATION OF SIGMA RECEPTOR LIGANDS The sigma receptor ligands listed in Tables 1, 2 and 3 were synthesized according to one of twelve synthetic procedures (Methods A-L) disclosed immediately below. METHODS METHOD A: R(-)-N-(3-Phenylpropyl)-l-phenyl-2-aminopropane Hydrochloride. A mixture of hydrocinnamaldehyde (1.11 g, 8.2 mmol) and R(-)-amphetamine (0.94 g, 7.0 mmol) in MeOH (20 L) was hydrogenated over Pt/C 5% (0.2 g) at room temperature until the theoretical amount of hydrogen was absorbed. The methanolic solution of the base was separated from the catalyst by filtration and was treated with 10% HC1 until the mixture was strongly acidic. The MeOH and H 2 0 were removed under reduced pressure with warming to give a crude solid, which was recrystallized several times from MeOH and MEK to give 1.6 g (80%) of colorless crystals, mp 215-217 β C. METHOD B: R(-)-N-(Cyclopropylmethyl)-l-phenyl-2-aminopropane Maleate. To a suspension of LiAlH 4 (1.49 g, 38 mmoL) in anhyd. ether (50 mL) was added a solution of N-(σ-methylphenylethyl)-2- cyclopropylcarboxamide (1.5 g, 74 mmol) in anhyd. Et 2 0 (20 mL). The mixture was heated at reflux overnight, cooled to 0 β C and H 2 0 (2.5 mL) was added in a drop wise manner. This was followed by the addition of 2N NaOH solution (2.5 mL) and then H 2 0 (5 mL). After the inorganic precipitate was removed by filtration, the Et 2 0 solution was dried (anhyd. Na 2 S0 4 ) and treated with a solution of maleic acid (1.5 g in absolute EtOH (10 L). The product was collected by filtration, washed with Et 2 0 and recrystallized from 2-PrOH/Et 2 0 (3x) to afford 1.3 g (59%) of fine crystals: mp 162-163 β C. METHOD C: N-(3-Phenylpropyl)-l-(4-bromophenyl)-2-aminopropane Hydrochloride. A1H 3 was prepared by the addition of A1C1 3 (0.07g, 0.5 mmol) to a suspension of LiAlH 4 (0.064 g, 1.7 mmol) in Et 2 0 (50 mL) at 0 β C under a nitrogen atmosphere. A solution of N- hydrocinnamoyl-l-(4-bromophenyl)-2-aminopropane (100 mg, 0.29 mmol) in dry Et 2 0 (10 mL) was added in a drop wise manner, to the A1H 3 solution at 0 β C. After the addition was complete, the mixture was allowed to stir for 0.5 h at the same temperature. Excess A1H 3 was decomposed by the addition of crushed ice (1 g) followed by 15% NaOH solution (2 mL). The mixture was filtered and the organic portion was separated, washed with H 2 0 (20, 10, 5 mL), dried (anhyd. MgS0 4 ) and treated with sufficient HC1 gas until precipitation was complete. The precipitate was collected by filtration and recrystallized from EtOH/Et 2 0 (4x) to give 20 mg (19%) of a finely divided powder: mp 176-178°C. METHOD D: N-(3-Phenylpropyl)-1-(3-trif1uoromethylphenyl)-2- aminopropane Hydrochloride. A mixture of l-(3- trifluoromethylphenyl)-2-propanone (102 mg, 0.50 mmol), 3-phenyl- 1-propylamine (86 mg, 0.64 mmol), glacial acetic acid (8 mg, 0.13 mmol), and MeOH (2 mL) was allowed to stir at room temperature for 0.5 h. To this mixture was added over a 4-h period sodium borohydride (19 mg, 0.50 mmol) and the mixture was allowed to stir at room temperature for 20 h. The solvents were removed by warming under reduced pressure to give a small amount of an oil which was cooled and treated with 10% HC1. The crude product separated as a white solid, 122 mg (68%), mp 135-145 β C. The crystals were dissolved in H 2 0 and the solution was extracted with Et 2 0. The H 2 0 portion was separated, the H 2 0 was evaporated, and the crystals reformed; recrystallization from acetone gave 66 mg (37%) of colorless crystals, mp 167-169'C. METHOD E: R(-)-N-Benzyl-l-phenyl-2-aminopropane Hydrochloride. To a mixture of R(-)-amphetamine sulfate (0.633 g, 3.4 mmol), benzaldehyde (0.547 g, 5.2 rnrnol), MeOH (3 mL), and glacial acetic acid (0.5 g) was added sodium cyanoborohydride (0.263 g, 4.0 mmol) at room temperature over a 1-h period. During this addition, the pH was maintained at pH 5.5-6.0 by the addition of additional glacial acetic acid (0.25 g). After stirring 20 h at room temperature, the MeOH was removed by warming under reduced pressure. The residue was treated with an excess of 10% NaOH and the product extracted into Et 2 0. The product was then extracted into an excess of 10% HC1 solution; the aqueous layer was decanted and the water was removed by warming under reduced pressure to give the crude product, 0.5 g (56%), mp 170-174 β C. After several recrystallizations from MeOH-MEK, the colorless crystals weighed 0.46 g (51%), mp 173-175 β C. METHOD F: R(-)-N-(2-Phenoxyethyl)-l-phenyl-2-aminopropane Hydrochloride. In a 5-mL reaction vial was placed R(-)- amphetamine (0.288 g, 2.1 mmol) and 2-phenoxyethyl chloride (0.335 g, 2.1 mmol). The vial was sealed and heated at 95 β C for 20 h. The reaction mixture was cooled, washed repeatedly with Et 2 0 to give the crude product which melted at 155-160 β C. Recrystallization (3x) using MeOH and MEK gave colorless*crystals that weighed 50 mg (8%), mp 178-179 β C. METHOD G: R(-)-N-(3-Phenyl-3-oxopropyl)-l-phenyl-2-aminopropane Hydrochloride. A mixture of R(-)-amphetamine hydrochloride (0.259 g, 1.5 mmol), acetophenone (0.635 g, 5.3 mmol), paraformaldehyde (87 mg), MeOH (1.2 mL), and cone. HC1 (1 drop) was placed in a 5-mL reaction vial, stirred, and heated at 65 β C for 24 h. After removing the solvent using reduced pressure and warming, the reaction mixture (which became partially solid) was dissolved in H 2 0 (5 mL) and was extracted twice with hexane (10 mL). The aqueous portion was made basic with 10% NaOH and the product extracted into hexane (10 mL). The product was then extracted into a 10% HC1 solution and the H 2 0 and excess HC1 were removed with warming under reduced pressure to form the crude solid, mp 135-144 Q C. Repeated recrystallizations using MEK and acetone gave 50 mg (11% yield) of colorless crystals, mp 146- 147 β C. METHOD H: (+)-σ-[N-(3-phenylpropyl)amino]propiophenone Hydrochloride. A mixture of hydrocinnamaldehyde (2 g, 15 mmoL) and norephedrine (2.18 g, 14.4 mmol) in EtOH (100 mL) was hydrogenated over a catalytic amount of Pd/C 10%, at room temperature. A hydrogen uptake slightly in excess of theory was obtained. The suspension was filtered and the filtrate was treated with 2N HC1 (30 mL). The acid solution was evaporated to give a residual solid, which was recrystallized twice from EtOH/Et 2 0 to give 2.34 g (55%) of needles: mp 211-213 β C. An ice-cooled mixture of CH 2 C1 2 (20 mL) and pyridine (0.8 g, 10 mmol) was treated with dry Cr0 3 (0.5 g, 5 mmol), which was added in portions within a 30-min period. The purple-brown mixture was stirred at room temperature for 2 h. A solution of the amino alcohol prepared above (0.23 g, 1.24 mmol) in CH 2 C1 2 (5 mL) was added to the pyridine-Cr0 3 mixture all at once with vigorous stirring. After 15 in, the yellow organic layer was decanted from the black, sticky precipitate and extracted with 5% NaOH (100 L). The organic portion was filtered through a bed of anhyd. Na 2 S0 4 and evaporated to dryness. The oily residue was treated with cone. HC1 (5 mL), warmed, and the mixture was evaporated to dryness. The solid residue was recrystallized from 2-PrOH/Et 2 0 (2x) to give 150 mg (40%) of the hydrochloride salt: mp 154-155'C (solidified and melted again at 170-172 β C). METHOD I: N-Benzyl-2-phenylmorpholine Hydrochloride. To a solution of N-(2-hydroxyethyl)-N-(benzoylmethyl)-benzylamine hydrochloride (0.50 g, 1.6 mmol) and MeOH (5 mL) at 5 β C was added with stirring over 4 h sodium borohydride (0.213 g, 5.6 mmol). The reaction was allowed to warm to room temperature over 18 h; an additional amount of sodium borohydride (70 mg, 1.8 mmol) was added, and the reaction was stirred for an additional 24 h. A small amount of H 2 0 (1 ml) was added to the mixture and the solvents removed by warming under reduced pressure. Water (6 mL) and Et 2 0 (12 mL) were added to the reaction mixture; the ether layer was removed and the Et 2 0 evaporated under reduced pressure to give the crude liquid product as the free base (0.42 g). Treatment of the free base with cold cone. HC1 (1 L) followed by warming under reduced pressure to remove the H 2 0 and excess HC1 afforded the crude product hydrochloride. Recrystallization from acetone gave colorless crystals of the amine hydrochloride 0.38 g (77%), mp 140-143 β C. A portion of these crystals (35 mg, 0.11 mmol) was heated at 125 β C with cone. HC1 (0.17 g) in a sealed reaction vial for 1.25 h. The H 2 0 and excess HC1 were removed by warming under reduced pressure to give 40 mg of the crude, tan product, mp 201- 205 β C. Two recrystallizations from acetone gave 21 mg (66%) of the substituted morpholine hydrochloride as colorless crystals, mp 211-212°C. METHOD J: l-(4-Phenylbutyl)-4-(4-chlorophenyl)-l,2,5,6- tetrahydropyridine Maleate. To a stirred mixture of glacial acetic acid (1.9 g, 31.7 mmol) and acetic anhydride (0.4 g, 4 mmol) was added slowly (85%) orthophosphoric acid (0.43 g, 4 mmol). After the exothermic reaction had subsided, 4- phenylaminobutane (0.58 g, 4 mmol), paraformaldehyde (0.36 g) and 4-chloro-σ-methylstyrene (0.62 g, 4 mmol) were added. The reaction mixture was stirred at 115 β C for 4 h . then allowed to stand at room temperature for 2 days. The mixture was diluted with H 2 0 (10 mL), extracted with hexane and the aqueous layer made basic with Na 2 C0 3 . The crude product was extracted into hexane, dried over anhyd. K 2 C0 3 , and the solvent removed by evaporation. The crude free base was recrystallized from H 2 0- MeOH to give the purified free base (mp 87-90 β C) which was dissolved in EtOH and treated with an Et 2 0 solution of maleic acid to give the maleate salt. Recrystallization from EtOH-Et 2 0 gave 0.6 g (35% yield) of fine crystals, mp 162-164 β C. METHOD K: N-(3-Phenylpropyl)-1-(4-hydroxyphenyl)-2-aminopropane Hydrobromide. A suspension of the free base of N-(3- phenylpropyl)-l-(4-methoxyphenyl)-2-aminopropane (200 mg, 0.63 mmol) in 48% HBr was heated at reflux for 6 h. The mixture was filtered while hot and the filtrate allowed to cool to room temperature to give crystals. The crystals were collected by filtration and recrystallized from Et0H-Et 2 0 to give 200 mg (88% yield) of the hydrobromide salt, mp 159-160 β C. METHOD L: l-(3-Chlorophenyl)-4-(3-phenylpropyl)piperazine Hydrochloride. To a stirred solution of diborane:di ethyl sulfide complex (2M) in THF (30 L) was added drop wise a solution of dry THF (25 mL) and l-(3-chlorophenyl)-4-(3- phenylpropionyl)piperazine (1.28 g, 3.86 mmol). The reaction mixture was stirred at room temperature for 18 h, quenched by the addition of MeOH-HCl (25 L), and the solvents removed under reduced pressure. Additional MeOH was added and removed under reduced pressure to give a tan solid. This was dried for 18 h under vacuum then recrystallized from MEK to give 0.9 g (67%) of colorless crystals, mp 168-169 β C. - a RS ■ Recrystallization solvent: ethyl acetate (A), acetonitrlle (C), absolute ethanol (E), 2-proρanol (I), 2-butanone (K), methanol (H), acetone (N), iethyl ether (0). b ANAl » Microanalyβis. All neu compounds were submitted for elemental analysis and found values are within 0.4X of theory. c fenzoate Salt (mp 101-103*0 previously reported: i. Pharm. Sci. 64:1462 (1975). Compound AD-51 was converted to the benzoate salt for purpose of dentification: mp 100-101*C. "Literature (J. Pharm. Sci. 64:1462 (1975)) mp 133*C for p-tolueneβulfonate salt. A small sample of AH-75 was converted to this salt for purpose of omparison: mp 132-133*C. *NAPH-1 * 1-Naphthyl. f NAPH-2 ■ 2-Haphthyl. 9 Mal ■ maleate salt. ''There are other ways in which the Series I compounds might have been prepared than the method shown. Table 2: Properties of Additional Series I Compounds. *See footnote a, Table 1. b See footnote b, Table 1. 'Literature (Chem. Abstr. 49:7812 (1955)), mp 201-202*C. ''There are other ways In which the Series I compounds might have been prepared than the method shown. Table 3: Properties of Series II Compounds. Q c r 2 AH-128 o-o 3 A AH-127 3 (t) A 4 J AD-34 1 (*) I *See footnote a, Table 1. b See footnote b, Table 1. c Literβture (Chem. Abstr. 60:12028). mp 205*207*C. d Llterβture (J. Med. Chem. 9:555 (1966)), mp 214-216*C. e There sre other ways In which the Series II compounds night have been prepared than the method shown. EXAMPLE 2 SIGMA. PCP AND DOPAMINE RECEPTOR BINDING ASSAYS Methods Sigma receptor binding assays using guinea pig brain membrane ho ogenates and the radioligand [ 3 H]DTG were conducted as described by Weber et al ., P.N.A.S. (USA) 83.8784-8788 (1986) . Briefly, frozen whole guinea-pig brains (Biotrol, Indianapolis, IN) were homogenized in 10 volumes (w/v) of ice-cold 320 mM sucrose using a Brinkman polytron. The homogenate was centrifuged at 1,000 x g for 20 minutes at 4'C. The supernatant was centrifuged at 20,000 x g for 20 minutes at 4 β C. The resulting pellet was resuspended in 10 initial volumes of 50 M Tris/HCl buffer at pH 7.4 and centrifuged at 20,000 x g for 20 minutes at 4°C. The resulting pellet was resuspended in 5 initial volumes ice-cold 50mM Tris/Hcl (pH .4), and the final volume was adjusted to yield a protein concentration of 3 mg/nϊl . Aliquots of 20-ml were stored at -70"C until used, with no detectable loss of binding. For [ 3 H]DTG binding assays, the frozen membrane suspensions were thawed and diluted 1:3 in 50 mM Tris/HCl (pH 7.4). To 12 x 75 mm polystyrene test tubes were added 0.8 ml of diluted membrane suspension, 0.1 ml of [ 3 H]DTG (Dupont/NEN) to yield a final concentration of 1.4 nM, and 0.1 ml of unlabelled drugs or buffer. The protein concentration in the 1-ml final incubation volume was 800 ug/ l, corresponding to 32 mg of brain tissue (original wet weight) and to a tissue concentration within the linear range for specific binding. Non-specific binding was defined as that remaining in the presence of 10 uM haloperidol. Incubations were terminated after 90 minutes at room temperature by addition of 4 ml of ice-cold 50mM Tris/HCl (pH 7.4) and rapid filtration of the membrane suspension through Whatman GF/B glass-fiber filters under vacuum, using a 48-well cell harvester (Brandel). The filters were washed 2 times with 4 ml of 50 mM Tris/HCl (pH 7.4). Each filter was suspended in 10 ml Cytoscint (ICI), and radioactivity was measured by liquid scintillation spectrometry at a counting efficiency of approximately 50%. IC 50 values were determined by non-linear regression analyis. PCP receptor binding assays against - 3 H-MK-801 were conducted as described by Keana et al ., Proc. Nat! . Acad. Sci (USA) 86:5631-5635 (1989); Keana et al .. Life Sciences 43:965-973 (1988). For (+) 3 H-MK-801 binding, 1 nM of radioligand was incubated with about 100 ug of thawed rat brain membrane protein for 4 hr at room temperature. The assays were carried out in 5 mM Tris/acetate and were stopped by rapid filtration through Whatman GF/B or Schleicher & Schuell no. 32 glass fiber filters (presoaked in 0.05 % polyethylenamine). Dopamine DI and D2 receptor binding assays were performed as described by Billard et al.. Life Sci. 35:1885-1893 (1984) using [ 3 H]SCH-23390 for the DI receptors and [ 3 H]domperidone for the D2 receptors (Baudry et al .. Arch. Pharmacol. 308:231-237 (1979). Rat striatal membranes were prepared from frozen tissue by Poltron homogenization in 25 volumes of ice cold Tris-EDTA buffer (50 mM Tris-HCl, 1 M EDTA, pH 7.4 at 4 β C). The homogenate was centrifuged at 48,000 x g for 10 min. at 4 β C, and the pellet was resuspended in 25 volumes of the same buffer. This suspension was then incubated at 37"C for 15 min., followed by recentrifugation as before. The resulting pellet was resuspended in 267 volumes of assay buffer (50 mM Tris-HCl, 120 mM NaCl , 5 M KC1, 2 mM CaCl 2 , 1 mM MgCl 2 , pH 7.4 at 37 °C). The binding assays were conducted with 100 uL of [ 3 HJSCH- 23390 or [ 3 H]domperidone (to give about 1 nM final), 100 uL of buffer or drug solution, and 800 uL of membrane suspension (to give about 250 ug of striatal membrane protein per assay). The tubes were incubated at 37°C for 60 min. The assays were stopped by rapid filtration over Schleicher & Schuell #32 or Whatman GF/B glass fiber filters (presoaked in 0.5% polyethyleneimine for [ 3 H]domperidone binding), followed by two 3 mL washes of ice cold buffer using a Brandel cell harvester. After vigorous shaking, the filter disks were counted at 52% efficiency in 5 mL of Cytoscint (ICN). The results of these binding assays appear in Table 4. TABLE4 COMPOUND 190- siG siG VER IC50 (M) S.E.M. >10 -5 >ιo- R- 6.85X10 "7 2.50x10-8 2 >10 ,-5 R- 1.705xlθ "6 1.65x10 " >10 " CH 2 CH 2 CH 3 CLWOUND ISO- SIGM SIGW n PCP VER IC50 (M) S.E.M. IC50 (M) 1.22xl0- 7 1.65x10-8 2 >10 " HN- ! 6.24x10-8 9.00X10- 9 2 9.00X10 "6 4.71x10-8 5.75X10- 9 2 >10 "5 5.84x10-8 7.45x10-9 2 >10" 5 9.69x10-9 5.10X10- 10 2 >10 "5 CCMPOUND 9.15X10- 9 2.75X10- 9 2 >10 " 1.24x10-9 1.40X10 "10 2 >10 " 1.22X10" 7 2.50x10-9 2 >10 " 2.85x10- 5.20x10-9 2 >10 "5 >10 '5 6.60x10-9 1.79x10-9 2 >10 "5 l.OSxlO "8 0.00 >10 " 9 HN Γ-Ό +/- 493xl0 "8 2.95xl0 "9 * >10 9.32 >10 " (2) ±4.5 (3) +/- 6.17x10-9 3.70X10 "10 2 >10 "5 x> r C0MR0UNO ISO- SIGm siG 01 02 CP MER IC50 (M) S.E.M. IC50 (uM) IC50 (M) (n) +/- 9.11x10-9 6.15x10-10 2 >ιo- - 1.597xl0 "8 4.64xl0 "9 >10 "5 -5L - COMPOUND ISO- SIGm SIGm n PCP MER IC50 (M) S.E.M. IC50 (M) S S,,SJ - 2.88XIO- 7 2.00x10-9 2 >10 rS , S+ 3.26xl0- 8 2.05x10-9 2 >10 " R- 4.80xl0 "5 0.00 2 >10 '5 R- 4.95x10-6 5.00x10-8 2 >10' 5 R- 2.10X10 "5 2.00x10-6 2 >10" N O 2 ■ α*P0UND iso- siGm siGm PCP MER IC50 (M) S.E.M. IC50 (M) 08x10-8 6.50x10-1° 2 >10 ,-5 09x10-8 2.67x10-9 2 >10 -5 +/- 2.56x10-6 4.00x10-8 2 >10 -5 +A 2.59x10-7 1.90x10-8 2 >10 -5 o O i OGMPOLM) ISO- SIGm SIGm MER IC50 (M) S.E.M. (M) S+ 6.85x10-9 1.50x10-1° 2 1.45x10-9 2 >10 " 39 1.20x10-9 2.00x10-1° 2 >10 -5 5 >10 "5 6 1 The second set o numbers represent a second lot. * COMPOUM) ISO- SIGm siGm 01 02 PCP MER IC50(M) S.E.M. 50(uM) IC50 (M) (n) 2 >10 " 9 5.20x10-9 2.00x10-10 2 >10 " 2.27x10-8 2.10x10-9 2 >10 -5 1 3l +) 5.95x10 9 3.95xl0 "9 2 >10 "5 4 COMPOUND ISO- SIGm SIGm 01 02 PCP MER IC50 (M) S.E.M. ICSO(u) IC50 (M) (n) 7.50x10 i-lO >10 " 47 5.65x10-9 1.02x10-9 2 >10 " 8 2.70x10-9 2.00x10-1° 2 >10 " 9 >10 " 0 2.95x10-9 5x10 •11 >10 -5 COMPOUND iso- siGm siGm 01 02 CP MER IC50 (M) S.E.M. IC50 (t_M) IC50 (M) 4.23χl0 "9 1.42xl0 "9 4 2.99 .158 >10 "5 Results As can be seen in Table 4, the sigma receptor ligands of the present invention exhibit very high binding with respect to the sigma receptor and very low binding with respect to the PCP and DA receptors. Therefore, these sigma receptor ligands can be used for the treatment of mental illness without the extrapyramidal side effects of traditional neuroleptic agents caused by binding to the DA receptor. EXAMPLE 3 r 3 HlDTG BINDING ASSAYS Further sigma receptor binding assays against [ 3 H]DTG were conducted according to the procedure outlined in EXAMPLE 4. The results of these further studies are listed in Table 5. TABLE 5 SIGMA IC 50 (nM) COMPOUND MEAN SEM (n) N H !~© 11891.00 399.00 2 ci NH — ft 6393.67 4426.77 3 TABLE 5 (Cont.) SIGMA IC 50 (nM) COMPOUND MEAN SEM (n) NH N- ' V- Cl 1190.50 159.50 Q -O 2054.50 14.50 2 TABLE 5 (Cont.) SIGMA IC 50 (nM) COMPOUND MEAN SEM (n) TABLE 5 (Cont.) SIGMA IC 50 (nM) COMPOUND MEAN SEM (n) TABLE 5 (Cont. ) SIGMA IC 50 (nM) COMPOUND MEAN SEM (n) 75 13.57 1.67 3 TABLE 5 (Cont.) SIGMA IC 50 (nM) COMPOUND MEAN SEM (n) 78 cι -o- 01 0.23 2 130.10 18.163 TABLE 5 (Cont.) SIGMA IC 50 (nM) COMPOUND MEAN SEM (n) 81 OO ^ O 0.88 0.06 2 TABLE 5 (Cont.) SIGMA IC 50 (nM) COMPOUND MEAN SEM (n) 90 3 * 73 0.18 2 TABLE 5 (Cont. ) SIGMA IC 50 (nM) COMPOUND MEAN SEM (n) 95 o 16950.00 TABLE 5 (Cont.) SIGMA IC 50 (nM) COMPOUND MEAN SEM (n) Having now fully described this invention, it will be understood by those of skill in the art that the same can be practiced within a wide range of equivalent conditions, formulations, structural variations and other parameters without affecting the scope of the invention or any embodiment thereof.

Claims: WHAT IS CLAIMED IS: 1. A method of treating a human being suffering from schizophrenia or other psychoses, which comprises administering to said human a therapeutically effective amount of a compound of the formula: R 1 wherein: Ar is aryl, heteroaryl, substituted aryl or substituted heteroaryl, wherein the substituent is selected from the group consisting of chloro, fluoro, bromo, iodo, CF 3 , C,-C 6 alkoxy, C 2 - C 6 dial oxymethyl, C,-C 6 alkyl, cyano, C 3 -C 15 di alkyl ami noal kyl , carboxy, carboxamido, C.,-C β haloalkyl, haloalkyl thio, ally!, aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C 6 acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, C^Ce alkylthio, C j -Ce alkyl sul fonyl, C,-C β haloalkyl sul fonyl, alkyl sulfinyl, C,-C 6 haloalkyl sulfinyl , arylthio, C,-C 6 haloalkoxy, amino, C,-C 6 alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, N-al kyl carbamoyl , C 2 -C 15 N,N-di alkyl carbamoyl, nitro, C 2 -C 15 dial kyl sul famoyl ; R is hydrogen or alkyl; R 1 is selected from the group consisting of hydrogen, C-,-C β alkyl, C-,-C 6 alkoxy, fluoro, chloro, bromo and =0; or R and R 1 together form a morpholino, piperazinyl or piperidinyl ring; n is 0-5; W is -(CH 2 ) P - or -H H-, wherein p is 1-3; X is -(CH 2 ) q -, wherein q is 1-6; -(CH 2 ) r -C^C-(CH 2 ) r -, -(CH 2 ) r -CH=CH-(CH 2 ) r -; 0 // -(CH 2 ) r -C-(CH 2 ) r -; -(CH 2 ) r -Y-(CH 2 )--, wherein each r is independently 0-3 and wherein Y is 0 or S; or C^C β alkyl (wherein Z is hydrogen); Z is hydrogen, aryl or heteroaryl which may be substituted by chloro, fluoro, bromo, iodo, CF 3 , C,-C β alkoxy, C 2 -C 6 dialkoxy- methyl, C-,-C 6 alkyl, cyano, C 3 -C 15 dialkylaminoalkyl , carboxy, carboxamido, haloalkylthio, ally!, aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C 6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, C^Ce alkylthio, 0,-0 8 alkylsulfonyl , C^Ce haloalkylsulfonyl, C,-C β alkylsulfinyl, 0,-Cβ haloalkylsulfinyl, arylthio, C,-C β haloalkoxy, amino, C.-C β alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, C,-C 6 N-alkylcarbamoyl, C 2 -C 15 N,N-dialkylcarbamoyl, nitro and C 2 -C 15 dialkylsulfamoyl; wherein said compound exhibits high binding activity with respect to the sigma receptor. 2. A method of treating a human being suffering from schizophrenia or other psychoses, which comprises administering to said human a therapeutically effective amount of a compound of the formula: wherein: R is hydrogen or 0,-Ce alkyl; Ar is aryl, heteroaryl, substituted aryl or substituted heteroaryl, wherein said substituent is selected from the group consisting of chloro, fluoro, bromo, iodo, CF 3 , C.,-C 6 alkoxy, C 2 - C 6 dialkoxy ethyl, C,-C 6 alkyl, cyano, C 3 -C 15 dial kyl ami noal kyl , carboxy, carboxa ido, haloalkyl , C,-C β haloalkylthio, ally!, aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C 6 acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, alkylthio, alkyl sul fonyl, hal oal kyl sul fonyl, C,-C 6 alkyl sulfinyl, hal oal kyl sulfinyl, arylthio, C,-C β haloalkoxy, amino, 0,-Cg alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, 0,-Cg N-al kyl carbamoyl , C 2 -C 15 N,N-di alkyl carbamoyl, nitro and C 2 -C 15 di alkyl sul fa oyl ; R 1 is selected from the group consisting of hydrogen, C.,-C 6 alkyl, C,-C 6 alkoxy, fluoro, bromo, chloro, iodo and =0; or R and R 1 together form a morpholii.o, piperazinyl or piperidinyl ring; n is 0-5; X is -(CH 2 ) q -, wherein q is 1-6; -(Crl 2 ) r -CsC-(CH 2 ) r -, wherein r is 0-3; -(CH 2 ) r -CH=CH-(CH 2 ) r -; 0 // -(CH 2 ) r -C-(CH 2 ) r -; ■ (CH 2 ) r -Y-(CH 2 ) r -, wherein each r is independently 0-3 and wherein Y is 0 or S; or alkyl (wherein Z is hydrogen); Z is hydrogen, aryl or aryl substituted by chloro, fluoro, bromo, iodo, CF 3 , C^Cg alkoxy, C 2 -C 6 dialkoxymethyl, C,-C β alkyl, cyano, C 3 -C 15 di alkyl ami noal kyl , carboxy, carboxamido, haloalkyl, Cι~C β haloalkylthio, ally!, aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C 6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C β heterocycloalkyl, C,-C 6 alkylthio, 0,-Cg al kyl sul fonyl , C,-Cg hal oal kyl sul fonyl , C-,-C 6 alkyl sulfinyl, C-,-C 6 hal oal kyl sulfinyl, arylthio, C,-C β halo¬ alkoxy, amino, alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, C,-Cg N-al kyl carbamoyl, C 2 -C 15 N,N-dial kyl carbamoyl , nitro and C 2 -C 15 di alkyl sul famoyl ; wherein said compound exhibits high binding activity with respect to the sigma receptor. 3. The method of claim 2, wherein said compound is selected from the group consisting of N-phenethyl-1- phenyl i sopropyl ami ne , N-phenyl propyl - 1-phenyl - i sopropyl ami ne , N- (2-phenoxy)ethyl -1-phenyl isopropyl amine, N- (3-phenyl -3-propanon- 1-yl ) -1-phenyl isopropyl amine, N- (4- phenyl butyl )-l- phenyl isopropyl amine, N-(3-(l-naphthyl)propyl)-l- phenyl i sopropyl amine, N- (3- (2-naphthyl )propyl ) -1- phenyl isopropyl amine, N- (3-phenyl -2-propyn-l-yl) -1-phenyl - isopropyl ami ne, N- (3-phenyl propyl ) -l- (4- hydroxy phenyl ) isopropyl amine, N- (3-phenyl propyl )-l-(4- methoxy phenyl ) isopropyl amine, N- (3-phenyl propyl )-l-(3- bro ophenyl )isopropyl amine, N- (3-phenylpropyl ) -l-(4- bromophenyl ) i sopropyl ami ne, N- (3-phenyl propyl ) -1 - (3 , 4-di chl oro- phenyl)isopropylamine, N-(3-phenylpropyl)-l-(4- iodophenyl isopropyl ) amine, N- (3-phenylpropyl ) -1- (3- tri f 1 uoromethyl phenyl ) i sopropyl ami ne , N- (2-phenethyl ) -N-methyl - 1- phenyl isopropyl amine, N- (3-phenyl propyl) -1-phenyl propan-l-one-2- amine, N-(2-indane)-3-phenylpropylamine, N,N-di-((3- phenyl)propyl)amine, N-(2-(l-naphthyl)ethyl)-l- phenyli sopropyl amine, N- (2- (2-naphthyl) ethyl )-l- phenyl isopropyl amine, N- (2- (1 -naphthyl ) propyl ) -1- phenyl isopropyl amine, N- (2- (2-naphthyl )propyl ) -1- phenylisopropylamine, N-(4-phenylbutyl)-l-(2,5- dimethoxyphenyl) isopropyl amine, N-(4-phenylbutyl)-l-(4-bromo-2,5- di ethoxyphenyl) isopropyl amine, N-methyl -N-(4-phenyl butyl )-l- phenyl isopropyl amine, N-methyl -N-(5-phenylpentyl )-l- phenyl i sopropyl ami ne , N- (3- phenyl propyl )- 1 -( 4- ethoxy phenyl) isopropyl amine, N- (3-phenylpropyl )-l-(4- ethyl phenyl) isopropyl amine, N- (3-phenyl propyl )-l-(4- phenoxyphenyl ) i sopropyl ami ne, N-methyl -N- (3-phenyl propyl ) - 1 - (4- ethyl phenyl ) i sopropyl ami ne . 4. A method of treating a human being suffering from schizophrenia or other psychoses, which comprises administering to said human a therapeutically effective amount of a compound of the formula: R 1 wherein: R is hydrogen or C.-Cg alkyl; Ar is aryl, heteroaryl, substituted aryl or substituted heteroaryl, wherein the substituent is selected from the group consisting of chloro, fluoro, bromo, iodo, CF 3 , C,-Cg alkoxy, C 2 - C β dialkoxymethyl, 0,-Cg alkyl, cyano, C 3 -C 15 dialkylaminoalkyl , carboxy, carboxamido, haloalkyl , haloalkylthio, ally!, aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C β acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, alkylthio, C,-C 6 alkylsulfonyl , haloalkylsulfonyl, alkylsulfinyl, 0,-Cg haloalkylsulfinyl, arylthio, C,-C 6 haloalkoxy, amino, C,-C β alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, N-alkylcarbamoyl, C 2 -C 15 N,N-dialkylcarbamoyl, nitro and C 2 -C 15 dialkylsulfamoyl; R 1 is selected from the group consisting of hydrogen, 0,-Cg alkyl, C,-C 6 alkoxy, fluoro, chloro, bromo, iodo and =0; or R and R 1 together form a morpholino, piperazinyl or piperidinyl ring; n is 1-3; p is 1-3; X is -(CH 2 ) q -, wherein q is 1-6, -(CH 2 ) r -C≡C-(CH 2 ) r -, -(CH 2 ) r -CH=CH-(CH 2 ) r -, 0 II -(CH 2 ) r -C-(CH 2 ) r -, -(CH 2 ) r -Y-(CH 2 ) r -, wherein each r is independently 0-3 and wherein Y is 0 or S; or C^Cg alkyl; Z is hydrogen, aryl or heteroaryl which may be substituted by chloro, fluoro, bromo, iodo, CF 3 , C-,-C 6 alkoxy, C 2 -C β dialkoxy¬ methyl, alkyl, cyano, C 3 -C 15 di alkyl ami noal kyl , carboxy, carboxamido, C,-C β haloalkyl, haloalkylthio, ally!, aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C 6 carboxy! ic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, C,-C 6 alkylthio, 0,-Cg al kyl sul fonyl , C n -C 6 hal oal kyl sul fonyl, C,-C 6 al kyl sul f i nyl , C,-C β hal oal kyl sulfinyl, arylthio, 0,-Cg haloalkoxy, amino, 0,-Cg alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, 0,-Cg N-al kyl carbamoyl , C 2 -C 15 N,N-dialkylcarbamoyl, nitro and C 2 -C 15 di alkyl sul famoyl ; wherein said compound exhibits a high binding activity with respect to the sigma receptor. 5. The method of claim 4, wherein said compound is selected from the group consisting of N-(2-indane)-l- phenyl isopropyl amine, N-(2-indane) -3-phenylpropyl amine, N-(4,5- benzocycloheptyl) -1-phenyl isopropyl amine, N-(3 , 4- benzo c cl ohept l) -3- (phenyl) propyl am ine, N- (4, 5- benzocycloheptyl ) -3-phenylpropyl amine, N-(3,4-benzocyclohexyl )-l- phenyl isopropyl amine and N-3,4-benzocyclohexyl -3- phenyl propyl ami ne . 6. A method of treating a human being suffering from schizophrenia or other psychoses, which comprises administering to said human a therapeutically effective amount of a compound of the formula: wherein: R 2 is selected from the group consisting of hydrogen, chloro, fluoro, bromo, iodo, CF 3 , alkoxy, C 2 -C e dialkoxy¬ methyl, alkyl, cyano, C 3 -C 15 di alkyl ami noal kyl , carboxy, carboxamido, haloalkyl, C.-Cg haloalkylthio, ally! , aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C β acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -G 6 heterocycloalkyl, hal oal kyl sul fonyl , C,~ C 6 alkyl sulfinyl, C,-C 6 hal oal kyl sulfinyl , arylthio, C--C β halo- alkoxy, amino, C,-C 6 alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, C,-C β N-al kyl carbamoyl, C 2 -C 15 N,N-di alkyl carbamoyl, nitro and C 2 -C 15 di alkyl sul famoyl ; X is -(CH 2 )-, wherein q is 1-6, -(CH 2 ) r -CsC-(CH 2 ) r -, -(CH 2 ) r -CH=CH-(CH 2 ) r -, -(CH 2 ) r -Y-(CH 2 ) r -, wherein each r is independently 0-3 and wherein Y is 0 or S; or C^Cg alkyl (wherein Z is hydrogen); Z is aryl or heteroaryl which may be substituted by chloro, fluoro, bromo, iodo, CF 3 , 0,-Cg alkoxy, C 2 -C 6 dialkoxymethyl, C,-C 6 alkyl, cyano, C 3 -C 15 dial kyl ami noal kyl, carboxy, carboxamido, C-- C 6 haloalkyl, C^Cg haloalkylthio, ally!, aralkyl, C 3 -C 6 cyclo¬ alkyl, aroyl, aralkoxy, C 2 -C 6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl , C,-C β alkylthio, C,-C e al kyl sul fonyl , C^Cg hal oal kyl sul fonyl, C,- C 6 alkyl sulfinyl, C--C β hal oal kyl sulfinyl , arylthio, C^C g haloalkoxy, amino, C,-Cg alkyl-amino, dialkylamino, hydroxy, carba oyl, 0,-C 8 N-alkylcarbamoyl, C 2 -C 15 N,N-dialklcarbamoyl , nitro and C 2 -C 15 dialkylsulfamoyl; V is N or CM, wherein M is hydrogen, alkyl, C--C 6 alkoxy, hydroxy, fluoro, chloro, bromo or represents one half of a double bond with a neighboring endocyclic carbon; wherein said compound exhibits a high binding activity with respect to the sigma receptor. 7. The method of claim 6, wherein V is N, said compound having the formula 8. The method of claim 7, wherein said compound is selected from the group consisting of N-(3- trifl uoromethyl phenyl )-N' -phenethyl piperazine, N-(3- tr i f 1 uoromethyl phenyl ) -N ' - (4-phenyl butyl ) pi perazi ne , N- (3 - chl orophenyl ) -N ' -benzyl pi perazi ne , N- (3-chl orophenyl ) -N ' - (3- phenylpropyl )piperazine, N-(3-chlorophenyl ) -N ' - phenethyl piperazine, N-phenyl-N' -(3-phenylpropyl )piperazine, N- phenyl-N'- (3 -phenyl butyl) piperazine, N-naphthyl-N'-(3- phenyl propyl ) -pi perazi ne, N-phenyl -N' - (3- naphthyl propyl) piperazine, N-phenyl-N' -propyl piperazine, N-(4- chl orophenyl ) -N' - (3-phenylpropyl )piperazine, N-benzyl -N' - (4- phenyl butyl ) pi perazi ne , N-phenyl -N ' - (4- phthal i idobutyl )piperazine, and N-phenyl -N' -(5- phthal imi dopentyl ) pi perazi ne . 9. The method of claim 6, wherein V is CM, said compound having the formula 10. The method of cl aim 9, wherein said compound is selected from the group consisting of N-phenethyl -4- phenylpiperidine, N-phenethyl -4-phenyl -4-hydroxypiperidine, N- phenyl propyl -4-phenyl pi peri di ne, N-phenyl propyl -4-phenyl -4- hydroxypi peri dine, N-phenylpentyl -4-phenylpiperidine, N- phenyl butyl -4-phenyl pi peri dine, N- (3-phenyl propyl ) -4- (4- chl orophenyl ) -1,2, 5, 6-tetrahydropyri dine and N- (3-phenyl butyl ) -4- (4-chl orophenyl ) -1,2, 5, 6-tetrahydropyri dine. 11. A method of treating a human being suffering from schizophrenia and other psychoses, which comprises administering to said human a therapeutically effective amount of a compound of the formula: wherein a is 1-8; b is 1-8; R is hydrogen or alkyl; R 2 is independently selected from the group consisting of hydrogen, chloro, fluoro, bromo, iodo, CF 3 , C,-C 6 alkoxy, C 2 -C 6 dialkoxymethyl, C,-C β alkyl, cyano, C 3 -C 15 dialkylaminoalkyl , carboxy, carboxamido, C,-C 6 haloalkyl , haloalkylthio, ally!, aralkyl, C 3 -C β cycloalkyl, aroyl, aralkoxy, C 2 -C 6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, alkylthio, C,-C 6 al kyl sul fonyl , hal oal kyl sul fonyl, alkyl sulfinyl, C,-C 6 hal oal kyl sulfinyl , arylthio, 0,-C 8 haloalkoxy, amino, alkylamino, dialkylamino, hydroxy, carbamoyl, C,~C e N-al kyl carbamoyl , C 2 -C 15 N,N- dialkl carbamoyl, nitro and C 2 -C 15 d alkyl sul famoyl ; wherein said compound exhibits high binding activity with respect to the σ receptor. 12. A method of treating a human being suffering from schizophrenia or other psychoses, which comprises administering to said human a therapeutically effective amount of a compound having the Formula: wherein a is 1-8; b is 1-8; R is hydrogen or alkyl; R 2 is independently selected from the group consisting of hydrogen, chloro, fluoro, bromo, iodo, CF 3 , C--C 6 alkoxy, C 2 -C 6 dialkoxymethyl, C,-C 6 alkyl, cyano, C 3 -C 15 dial kyl ami noal kyl, carboxy, carboxamido, 0,-Cg haloalkyl , haloalkylthio, ally!, aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C 6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, C,-C 6 alkylthio, 0,-Cg al kyl sul fonyl , 0,-C 8 hal oal kyl sul fonyl, C,-C β alkyl sulfinyl, 0,-Cg hal oal kyl sulfinyl, arylthio, haloalkoxy, amino, 0,-Cg alkyl -amino, dialkylamino, hydroxy, carbamoyl, 0,-Cg N-al kyl carbamoyl, C 2 -C 15 N,N-dialkl carbamoyl, nitro and C 2 -C 15 di alkyl sul famoyl ; and wherein said compound exhibits high binding activity with respect to the σ receptor. 13. A method of treating a human being suffering from schizophrenia or other psychoses, which comprises administering to said human a therapeutically effective amount of a compound having the formula: wherein; Ar is aryl, heteroaryl, substituted aryl or substituted heteroaryl, wherein the substituent is selected from the group consisting of chloro, fluoro, bromo, iodo, CF 3 , C,-C 6 alkoxy, C 2 - C 6 dialkoxymethyl, alkyl, cyano, C 3 -C 15 d i alkyl ami noal kyl , carboxy, carboxamido, haloalkyl, haloalkylthio, ally!, aralkyl, C 3 -C e cycloalkyl, aroyl, aralkoxy, C 2 -C β acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C e heterocycloalkyl, alkylthio, 0,-Cg al kyl sul fonyl , C,-C e hal oal kyl sul fonyl, C,-C e alkyl sulfinyl, hal oal kyl sulfinyl, arylthio, C,-C 6 haloalkoxy, amino, C t -C β alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, C,-C β N-al kyl carbamoyl, C 2 -C 15 N,N-di alkyl carbamoyl, nitro and C 2 -C 15 dial kyl sul famoyl; X is -(CH 2 ) q -, wherein q is 1-6, -(CH 2 ) r -C=C-(CH 2 ) r -, -(CH 2 ) r -CH=CH-(CH 2 ) r -, 0 // -(CH 2 ) r -C-(CH 2 ) r -, -(CH 2 ) r -Y-(CH 2 ) r -, wherein each r is independently 0-3 and wherein Y is 0 or S; or 0,-Ce alkyl ; Z is hydrogen, aryl or heteroaryl which may be substituted by chloro, fluoro, bromo, iodo, CF 3 , C^Cg alkoxy, C 2 -C β dialkoxy¬ methyl, C-,-C β alkyl, cyano, C 3 -C 15 dial kyl ami noal kyl, carboxy, carboxamido, haloalkyl, haloalkylthio, ally!, aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C 6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, C,-C 6 alkylthio, 0,-Cg al kyl sul fonyl , C,-C 6 hal oal kyl sul fonyl, 0,-Cg alkyl sulfinyl, C,-C β hal oal kyl sulfinyl, arylthio, 0,-Cg haloalkoxy, amino, C,-C β alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, N-al kyl carbamoyl , C 2 -C 15 N,N-di alkyl carbamoyl, nitro and C 2 -C 15 di alkyl sul famoyl ; wherein said compound exhibits high binding activity with respect to the σ receptor. 14. A method of treating a human being suffering from schizophrenia or other psychoses, which comprises administering to said human a therapeutically effective amount of a compound having the formula: R 1 R Cy— (CH) n -NH-X-Z wherein n is 0-5; Cy is C 3 -C 8 cycloalkyl; R is hydrogen or C,-C e alkyl; R is independently selected from the group consisting of hydrogen, C,-C 6 alkyl, 0,-Cg alkoxy, fluoro, chloro, bromo, iodo and =0; X is -(CH 2 ) q -, wherein q is 1-6; -(CH 2 ) r -C≡C-(CH 2 ) r -, wherein r is 0-3; -(CH 2 ) r -CH=CH-(CH 2 ) r -; _ (CH 2 ) r -Y-(CH 2 ) r -, wherein each r is independently 0-3 and wherein Y is 0 or S; or C,-C 6 alkyl (wherein Z is hydrogen); and Z is hydrogen, aryl or heteroaryl which may be substituted by chloro, fluoro, bromo, iodo, CF 3 , j-Cg alkoxy, C 2 -C β dialkoxy¬ methyl, C.-C 8 alkyl, cyano, C 3 -C 15 di alkyl ami noal kyl , carboxy, carboxamido, C,-C 6 haloalkyl, haloalkylthio, ally!, aralkyl, C 3 -C β cycloalkyl, aroyl, aralkoxy, C 2 -C 6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, C,-C 6 alkylthio, C,-Cg alkyl sul fonyl, hal oal kyl sul fonyl, alkyl sulfinyl, hal oal kyl sulfinyl , arylthio, C^- 6 haloalkoxy, amino, C,-C e alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, N-al kyl carbamoyl, C 2 -C 15 N,N-di alkyl carbamoyl, nitro and C 2 -C 15 di alkyl sul famoy ; wherein s?.id compound exhibits high binding activity with respect to the σ receptor. 15. A method of treating a human being suffering from schizophrenia or other psychoses, which comprises administering to said human a therapeutically effective amount of a compound having the formula: wherein X 1 is -(CH 2 ) r -CsC-(CH 2 ) r -, wherein each r is 0-3 independently; -(CH 2 ) r -CH=CH-(CH 2 ) r -; -(CH 2 ) r -C-(CH 2 ) r -; -(CH 2 ) r -Y-(CH 2 ) r -, wherein Y is 0 or S; or C-|-Cg alkyl (wherein Z is hydrogen); R 2 is independently selected from the group consisting of hydrogen, chloro, fluoro, bromo, iodo, CF 3 , C,-C β alkoxy, C 2 -C e dialkoxymethyl, C,-Cg alkyl, cyano, C 3 -C 15 dial kyl ami noal kyl, carboxy, carboxamido, haloalkyl, C,-C β haloalkylthio, ally!, aralkyl, C 3 -C 6 cycl oal kyl , aroyl, aralkoxy, C 2 -C β . carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C e heterocycloalkyl, C,-C 6 alkylthio, C.-C 6 alkyl sul fonyl, hal oal kyl sul fonyl, 0,-Cg alky 1 sul finyl, hal oal kyl sulfinyl, arylthio, C-,-C β haloalkoxy, amino, alkyl -amino, dialkylamino, hydroxy, carbamoyl, 0,-Cg N-al kyl carbamoyl, C 2 -C 15 N,N-dialkl carbamoyl, nitro and C 2 -C 15 di alkyl sul famoyl ; V is N or CM, wherein M is hydrogen, alkyl, alkoxy, fluoro, chloro, bromo, trifluoromethyl, hydroxy or one half of a double bond with the neighboring endocyclic carbon; X is -(CH 2 ) q -, wherein q is 1-6; -(CH 2 ) r -C≡C-(CH 2 ) r -, wherein r is 0-3; -(CH 2 ) r -CH=CH-(CH 2 ) r -; 0 // -(CH 2 ) r -C-(CH 2 ) r -; -( c H 2 ) r -Y-(CH 2 ) r -, wherein each r is independently 0-3 and wherein Y is 0 or S; or C,-Cg alkyl (wherein Z is hydrogen); and Z is hydrogen, aryl or heteroaryl which may be substituted by chloro, fluoro, bromo, iodo, CF 3 , 0,-Cg alkoxy, C 2 -C 6 dialkoxy¬ methyl, C,-C β alkyl, cyano, C 3 -C 15 dial kyl ami noal kyl, carboxy, carboxamido, haloalkylthio, ally!, aralkyl, C 3 -C β cycloalkyl, aroyl, aralkoxy, C 2 -C 6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, C n -C 6 alkylthio, alkyl sul fonyl, C-,-C 6 hal oal kyl sul fonyl, C,-C e alkyl sulfinyl, C,-Cβ hal oal kyl sulfinyl, arylthio, C,-C β haloalkoxy, amino, C,-C β alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, C,-Cg N-al kyl carbamoyl, C 2 -C 15 N,N-di alkyl carbamoyl, nitro and C 2 -C 15 dial kyl sul famoyl; wherein said compound exhibits high binding activity with respect to the σ receptor. 16. The method of any one of claims 1, 2, 4, 6 or 11-15, wherein said compound is administered as part of a pharmaceutical composition comprising a pharmaceutically acceptable carrier. 17. A compound of the formula wherein: R i s hydrogen or methyl ; Ar is aryl, heteroaryl, substituted aryl or substituted heteroaryl, wherein the substituent is selected from the group consisting of chloro, fluoro, bromo, iodo, CF 3 , C,-C β alkoxy, C 2 - C e dialkoxymethyl, alkyl, cyano, C 3 -C 15 di alkyl ami noal kyl , carboxy, carboxamido, haloalkyl, haloalkylthio, ally!, aralkyl, C 3 -C β cycloalkyl, aroyl, aralkoxy, C 2 -C β acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C β heterocycloalkyl, C^Cg alkylthio, C,-C β alkyl sul fonyl, C n -Cg hal oal kyl sul fonyl, 0,-Cg alkyl sulfinyl, C^Cg hal oal kyl sulfinyl, arylthio, alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, 0,-Cg N-al kyl carbamoyl, C 2 -C 15 N,N-di alkyl carbamoyl, nitro and C 2 -C 15 di alkyl sul famoyl ; R 1 is selected from the group consisting of hydrogen, C,-C 6 alkyl, 0,-Cg alkoxy, fluoro, chloro, bromo, iodo and =0; or R and R 1 together form a morpholino ring; n is 0-5; W is -(CH 2 ) P - or -H H-, wherein p is 1-3; X is -(CH 2 ) q -, wherein q is 3-6; -(CH 2 ) r -C≡C-(CH 2 ) r -, -(CH 2 ) r -CH=CH-(CH 2 ) r -; 0 // -(CH 2 ) r -C-(CH 2 ) r -; or -(CH 2 ) r -Y-(CH 2 ) r -, wherein each r is independently 0-3 and wherein Y is 0 or S; Z is aryl or heteroaryl which may be substituted by chloro, fluoro, bromo, iodo, CF 3 , alkoxy, C 2 -C 6 dialkoxymethyl, C,-Cg alkyl, cyano, C 3 -C 15 dial kyl aminoal kyl, carboxy, carboxamido, C-,- C 6 haloalkyl, haloalkylthio, ally!, aralkyl, C 3 -C 6 cyclo¬ alkyl, aroyl, aralkoxy, C 2 -C 6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, C,-C 6 alkylthio, l kyl sul fonyl , C,-Cg haloalkyl sul fonyl, C-,- C 6 alkyl sulfinyl hal oal kyl sulfinyl , arylthio, halo- alkoxy, amino, C τ -C 6 alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, C,-C 6 N-al kyl carbamoyl, C 2 -C 15 N,N-di alkyl carbamoyl, nitro and C 2 -C 15 dial kyl sul famoyl; wherein said compound exhibits high binding activity with respect to the sigma receptor. 18. A compound of the formula: R 1 R Ar — (CH) n -N-X-Z wherein: R is hydrogen or C,-C 6 alkyl; Ar is aryl, heteroaryl, substituted aryl, or substituted heteroaryl, wherein said substituent is selected from the group consisting of chloro, fluoro, bromo, iodo, CF 3 , C,~C β alkoxy, C 2 - C 6 dialkoxymethyl, C n -C 6 alkyl, cyano, C 3 -C 15 dial kyl ami noal kyl, carboxy, carboxamido, haloalkyl, C-,-C 6 haloalkylthio, allyl, aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C 6 acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C β heterocycloalkyl, hal oal kyl sul fonyl, alkyl sulfinyl, C,-C 6 hal oal kyl sulfinyl , arylthio, C,-C 8 haloalkoxy, amino, 0,-Cg alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, N-al kyl carbamoyl , C 2 -C 15 N,N-di alkyl carbamoyl, nitro and C 2 -C 15 di alkyl sul famoyl ; R 1 is selected from the group consisting of hydrogen, alkyl, C^C g alkoxy, fluoro, chloro, bromo, iodo and =0; n is 0-5; X is -(CH 2 ) q -, wherein q is 3-6; -(CH 2 ) r -C≡C-(CH 2 ) r -, -(CH 2 ) r -CH=CH-(CH 2 ) r -; 0 // -(CH 2 ) r -C-(CH 2 ) r -; or -(CH 2 ) r -Y-(CH 2 ) r -, wherein each r is independently 0-3 and wherein Y is 0 or S; Z is aryl or heteroaryl which may be substituted by chloro, fluoro, bromo, iodo, CF 3 , alkoxy, C 2 -C 6 dialkoxymethyl , C-,-C e alkyl, cyano, C 3 -C 15 dial kyl ami noal kyl, carboxy, carboxamido, C,- C β haloalkyl, haloalkylthio, allyl, aralkyl, C 3 -C 6 cyclo¬ alkyl, aroyl, aralkoxy, C 2 -C 6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, alkylthio, C C e alkyl sul fonyl, C,-C 6 hal oal kyl sul fonyl, C.- C 6 alkyl sulfinyl, C--C 6 hal oal kyl sulfinyl , arylthio, 0,-Cg halo- alkoxy, amino, alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, 0,-Cg N-al kyl carbamoyl, C 2 -C 15 N,N-di alkyl carbamoyl, nitro and C 2 -C 15 di alkyl sul famoyl ; wherein said compound exhibits high binding activity with respect to the sigma receptor. 19. The compound of claim 18, wherein said compound is selected from the group consisting of N-phenyl propyl -1-phenyl - i sopropyl ami ne , N- ( 2-phenoxy) ethyl - 1-phenyl i sopropyl ami ne , N- (3 - phenyl -3-propanon-l-y ) -1-phenyl isopropyl amine, N- (4- phenyl butyl) -1-phenyl isopropyl -amine, N-(3-(l-naphthyl)propyl)-l- phenyl isopropyl amine, N- (3 -(2-naphthyl ) -propyl )-l phenyl isopropyl amine, N- (3-phenyl -2-propyn-l-yl) -1-phenyl i sopropyl ami ne , N- (3-phenyl propyl ) -1 - (4-hydroxy-phenyl ) i sopropyl amine, N- (3-phenyl propyl )-l-(4-methoxyphenyl) -isopropyl amine, N (3-phenylpropyl )-l-(3-bromophenyl )isopropylamine, N-(3 phenyl propyl )-l- (4-bromophenyl) isopropyl amine, N-(3 phenyl propyl )-l- (3, 4-dichl oro-phenyl ) isopropyl amine, N-(3 phenyl propyl ) - 1 - (4- i odophenyl ) i sopropyl ami ne , N- (3-phenyl propyl ) 1- (3 -trifluoromethyl phenyl) isopropyl ami ne,N- (3-phenyl propyl )-l phenylpropan-l-one-2-amine, and N,N-di-((3-phenyl)propyl)amine 20. A compound of the formula: R τ wherein: R is hydrogen or methyl; Ar is aryl, heteroaryl, substituted aryl or substituted heteroaryl, wherein the substituent is selected from the group consisting of chloro, fluoro, bromo, iodo, CF 3 , C,-C β alkoxy, C 2 - C 6 dialkoxymethyl, C,-C 6 alkyl, cyano, C 3 -C 15 di alkyl ami noal kyl , carboxy, carboxamido, haloalkyl, haloalkylthio, ally!, aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C 6 acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, C,-C β alkylthio, C.-C β al kyl sul fonyl , C^C g hal oal kyl sul fonyl, 0,-Cg alkyl sulfinyl, C,-C β hal oal kyl sulfinyl, arylthio, C,-Cg haloalkoxy, amino, C,-Cg alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, C,-C 6 N-al kyl carbamoyl , C 2 -C 15 N,N-di alkyl carbamoyl, nitro and C 2 -C 15 di alkyl sul famoyl ; R 1 is selected from the group consisting of hydrogen, alkyl, C,-C e alkoxy, fluoro, chloro, bromo, iodo and =0; or R and R 1 together form a morpholino ring; n is 1-3; p is 1-3; X is -(CH 2 ) q -, wherein q is 1-6, -(CH a ) r -C-C-(CH 2 ) r -, -(CH 2 ) r -CH=CH-(CH 2 ) r -, 0 // -(CH 2 ) r -C-(CH 2 ) r -, or -(CH 2 ) r -Y.-(CH 2 ) r -, wherein each r is independently 0-1 and wherein Y is 0 or S; Z is aryl or heteroaryl which may be substituted by chloro, fluoro, bromo, iodo, CF 3 , CτC 6 alkoxy, C 2 -C 6 dial oxymethyl , C,-C 6 alkyl, cyano, C 3 -C 15 dial kyl ami noal kyl , carboxy, carboxamido, C,- C β haloalkyl, C,-C 6 haloalkylthio, ally!, aralkyl, C 3 -C 6 cyclo¬ alkyl, aroyl, aralkoxy, C 2 -C 6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, -Cg alkylthio, C^C g al kyl sul fonyl , 0,-Cg hal oal kyl sul fonyl, C C 6 alkylsulfinyl , C,-C 6 hal oal kyl sulfinyl , arylthio, C,-C e halo¬ alkoxy, amino, alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, Cι-C 6 N-al kyl carbamoyl, C 2 -C 15 N,N-di alkyl carbamoyl, nitro and C 2 -C 15 di alkyl sul famoyl ; wherein said compound exhibits high binding activity with respect to the sigma receptor. 21. The compound of claim 20 selected from the group consisting of N-(2-indane)-l-phenylisopropylamine, N-(2-indane)- 3-phenyl propyl ami ne , N- (4 , 5-benzocycl oheptyl )- 1 - phenyl i sopropyl ami ne, N- (4, 5-benzocycl oheptyl) -3- phenyl propyl ami ne , N- (3 , 4-benzocycl ohexyl ) - 1-phenyl i sopropyl ami ne and N- (3 , 4-benzocycl ohexyl ) -3-phenyl propyl ami ne . 22. A compound of the formula: wherein: R 1 is selected from the group consisting of hydrogen, chloro, fluoro, bromo, iodo, CF 3 , C,-C 6 alkoxy, C 2 -C 6 dialkoxy¬ methyl, 0,-Cg alkyl, cyano, C 3 -C 15 di alkyl ami noal kyl , carboxy, carboxamido, C,-C 6 haloalkyl, C τ -C 6 haloalkylthio, ally!, aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C 6 acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, alkylthio, C,-C 6 al kyl sul fonyl , C,-C 6 hal oal kyl sul fonyl , C n - C 6 alkyl sulfinyl, hal oal kyl sulfinyl, arylthio, halo¬ alkoxy, amino, C^Cg alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, C,-C 6 N-al kyl carbamoyl, C 2 -C 15 N,N-di alkyl carbamoyl, nitro and C 2 -C 15 d i alkyl sul famoyl ; X is -(CH 2 ) r -C≡C-(CH 2 ) r -, -(CH 2 ) r -CH=CH-(CH 2 ) r -, 0 // -(CH 2 ) r -C-(CH 2 ) r -, or -(CH 2 ) r -Y-(CH 2 ) r -, wherein each r is independently 0-3 and Y is 0 or S; U is hydrogen, chloro, fluoro, bromo, iodo, C--C β alkoxy, C 2 -C 6 dialkoxymethyl, C t -C 6 alkyl, cyano, C 3 -C 15 di alkyl ami noal kyl , carboxy, carboxamido, C,-C β haloalkyl, C,-C β haloalkylthio, ally!, aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C β carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, 0,-Cg alkylthio, C,-C 6 al kyl sul fonyl , C,-C 6 hal oal kyl sul fonyl, 0,-Cg alkyl sulfinyl, C,-C β hal oal kyl sulfinyl, arylthio, C,-C 6 haloalkoxy, amino, alkyl-amino, dialkylamino, hydroxy, carbamoyl, N-alkylcarbamoyl , C 2 -C 15 N,N-dialklcarbamoyl, nitro and C 2 -C 15 dialkylsulfamoyl ; V is N or CM, wherein M is hydrogen, 0,-Cg alkyl, C.-C β alkoxy, fluoro, chloro, bromo, trifluoromethyl, hydroxy or one half of a double bond with the neighboring endocyclic carbon; wherein said compound exhibits high binding activity with respect to the sigma receptor. 23. The compound of claim 22, wherein V is N, said compound having the formula 24. A compound selected from the group consisting of N- (3-trifl uoromethyl phenyl )-N' -phenethyl piperazine, N-(3- chl orophenyl )-N' -benzyl piperazine and N-(3-chl orophenyl )-N'- phenethyl pi perazi ne . 25. A compound having the formula wherein: R 2 is selected from the group consisting of hydrogen, chloro, fluoro, bromo, iodo, CF 3 , C,-C β alkoxy, C 2 -C β dialkoxy¬ methyl, C,-C 6 alkyl, cyano, C 3 -C 15 di alkyl ami noal kyl , carboxy, carboxamido, C,-C 6 haloalkyl, C,-C 6 haloalkylthio, ally!, aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C β acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycl oal kyl , C,-C 8 alkylthio, C.-C 6 al kyl sul fonyl , Cj-Cg hal oal kyl sul fonyl, C,- C β al yl sulfinyl, C t -C β hal oal kyl sulfinyl, arylthio, halo- alkoxy, amino, C^Cg alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, C.,-C 8 N-al kyl carbamoyl, C 2 -C 15 N,N-di alkyl carbamoyl, nitro and C 2 -C 15 di alkyl sul famoyl ; X is -(CH 2 ) q -, wherein q is 1-6, -(CH 2 ) r -C≡C-(CH 2 ) r -, -(CH 2 ) r -CH=CH-(CH 2 ) r -, -(CH 2 ) r -C-(CH 2 ) r -, or -(CH 2 ) r -Y-(CH 2 ) r -, wherein each r is independently 0-3 and Y is 0 or S; U is hydrogen, chloro, fluoro, bromo, iodo, CF 3 , C-,-C β alkoxy, C 2 - C β dialkoxymethyl, C-,-C 6 alkyl, cyano, C 3 -C 15 di alkyl ami noal kyl , carboxy, carboxamido, 0,-Cg haloalkyl, C,-C β haloalkylthio, allyl, aralkyl, C 3 -C β cycloalkyl, aroyl, aralkoxy, C 2 -C 6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, C,-Cg alkylthio, C,-C 6 alkyl sul fonyl, hal oal kyl sul fonyl, C,-C 6 alkyl sulfinyl, hal oal kyl sulfinyl, arylthio, C-,-C β haloalkoxy, amino, alkyl-amino, dialkylamino, hydroxy, carbamoyl, C n -C β N-al yl carbamoyl, C 2 -C 15 N,N-dialkl carbamoyl, nitro or C 2 -C 15 di alkyl sul famoyl ; M is hydrogen, C,-C 6 alkyl, fluoro, chloro, bromo, trifluoromethyl, hydroxy or one half of a double bond with the neighboring endocyclic carbon; wherein said compound exhibits high binding activity with respect to the sigma receptor. 26. The compound of claim 25 selected from the group consisting of N-phenethyl-4-phenylpiperidine, N-phenethyl-4- phenyl-4-hydroxypiperidine, N-phenylpropyl-4-phenylpiperidine, N- phenylpropyl -4-phenyl -4-hydroxypiperidine, N-phenylpentyl-4- phenylpiperidine, N-phenylbutyl-4-phenylpiperidine, N-(3- phenylpropyl)-4-(4-chlorophenyl)-l,2,5,6-tetrahydropyridine and N- (3-phenyl butyl )-4-(4-chl orophenyl) -1,2, 5, 6-tetrahydropyridine. 27. A compound selected from the group consisting of N- (2-phenethyl)-N-methyl-l-phenylisopropylamine, N-(2-(l- naphthyl ) ethyl )- 1-phenyl isopropyl amine, N- (2- (1 -naphthyl )propyl )- 1-phenyl isopropyl amine, N- (2- (2-naphthyl ) ethyl ) - 1- phenyl isopropyl -amine, and N-(2-(2-naphthyl )propyl )-l- phenyl i sopropyl ami ne . 28. A compound having the formula: wherein a is 1-8; b is 1-8; R is hydrogen or C^Cg alkyl; R 2 is independently selected from the group consisting of hydrogen, chloro, fluoro, bromo, iodo, CF 3 , 0,-Cg alkoxy, C 2 -C 6 dialkoxymethyl, C,-C 6 alkyl, cyano, C 3 -C 15 dial kyl ami noal kyl, carboxy, carboxamido, C,-C 6 haloalkyl, C,-C β haloalkylthio, ally!, aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C 6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, 0,-0 6 alkylthio, C,-C 6 al kyl sul fonyl , C,-C 6 hal oal kyl sul fonyl, 0,-Cg alky 1 sul finyl, 0,-Cg hal oal kyl sulfinyl , arylthio, 0,-Cg haloalkoxy, amino, C,-Cg alkyl-amino, dialkylamino, hydroxy, carbamoyl, C-,-C β N-al kyl carbamoyl , C 2 -C 15 N,N-dialkl carbamoyl, nitro and C 2 -C 15 di alkyl sul famoyl ; wherein said compound exhibits high binding activity with respect to the σ receptor. 29. The compound of claim 28 selected from the group consi sti ng of N- (4-phenyl butyl ) phenethyl ami ne , N- (4-phenyl butyl ) - 3-phenyl propyl amine, N- (4-phenyl butyl ) -4-phenyl butyl amine , N- (4- phenyl butyl) benzyl amine, N- (4-phenyl butyl )-5-phenylpentyl amine, N-(δ-phenylpentyl) benzyl ami ne,N- (3-phenyl propyl) phenethyl amine, N- ( 5-phenyl pentyl ) phenethyl ami ne , N- (7-phenyl heptyl ) benzyl ami ne , N-(7-phenylheptyl)phenethyl amine, N-methyl -N- (2-phenethyl )-l- phenyl i sopropyl amine, N-methyl -N-( 5-phenyl pentyl )-l- phenyl isopropyl amine, and N-methyl -N- (3-phenyl propyl )-l- (4- propyl phenyl) isopropyl amine. 30. A compound having the formula: wherein a is 1-8; b is 1-8; R is hydrogen or C,-Cg alkyl; R 2 is independently selected from the group consisting of hydrogen, chloro, fluoro, bromo, iodo, CF 3 , 0,-Cg alkoxy, C 2 -C β dialkoxymethyl, alkyl, cyano, C 3 -C 15 di alkyl ami noal kyl , carboxy, carboxamido, 0,-Cg haloalkyl , C,-C β haloalkylthio, allyl, aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C 6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, alkylthio, al kyl sul fonyl , C,-C 6 hal oal kyl sul fonyl , C n -C β alkyl sul finyl, 0,-Cg hal oal kyl sulfinyl, arylthio, C,-Cg haloalkoxy, amino, 0,-Cg alkyl-amino, dialkylamino, hydroxy, carbamoyl, N-alkylcarbamoyl , C 2 -C 15 N,N-dialklcarbamoyl, nitro and C 2 -C 15 dialkylsulfamoyl ; and wherein said compound exhibits high binding activity with respect to the σ receptor. 31. The compound of claim 30 selected from the group consisting of N-(3-phenylpropyl)-2-naphthylethylamine and N- methyl-N-3-(2-naphthyl)propyl-1-phenylisopropylamine. 32. A compound having the formula: wherein; Ar is aryl, heteroaryl, substituted aryl or substituted heteroaryl, wherein the substituent is selected from the group consisting of chloro, fluoro, bromo, iodo, CF 3 , C,-C 6 alkoxy, C 2 - C β dialkoxymethyl, 0,-Cg alkyl, cyano, C 3 -C 15 di alkyl ami noal kyl , carboxy, carboxamido, C- j -Cg haloalkyl, C^Cg haloalkylthio, ally!, aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C 6 acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, C--C 6 alkylthio, 0,-Cg al kyl sul fonyl , C,-C 6 hal oal kyl sul fonyl, C,-Cg alkyl sulfinyl, hal oal kyl sulfinyl, arylthio, haloalkoxy, amino, C,-Cg alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, C,-Cg N-al kyl carbamoyl , C 2 -C 15 N,N-dialkylcarbamoyl , nitro and C 2 -C 15 di alkyl sul famoyl ; X is -(CH 2 ) q -, wherein q is 1-6, -(CH 2 ) r -C≡C-(CH 2 ) r -, -(CH 2 ) r -CH=CH-(CH 2 ) r -, 0 // -(CH 2 ) r -C-(CH 2 ) r -, -(CH 2 ) r -Y-(CH 2 ) r -, wherein each r is independently 0-3 and wherein Y is 0 or S; or Ci-C 6 alkyl; Z is hydrogen, aryl or heteroaryl which may be substituted by chloro, fluoro, bromo, iodo, CF 3 , Cι-C 6 alkoxy, C 2 -C β dialkoxy¬ methyl, Cι-C 6 alkyl, cyano, C 3 -C 15 dial kyl ami noal kyl, carboxy, carboxamido, Cι-C 6 haloalkyl, Cι-C 6 haloalkylthio, ally!, aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C 6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, Cι-C 6 alkylthio, Cι-C 6 al kyl sul fonyl , hal oal kyl sul fonyl , C n -C 6 alkyl sulfinyl , hal oal kyl sulfinyl , arylthio, Cι-C 6 haloalkoxy, amino, Cι-C 6 alkylamino, C 2 -C T5 dialkylamino, hydroxy, carbamoyl, Cι-C 6 N-al kyl carbamoyl, C 2 -C 15 N, N-di alkyl carbamoyl , nitro or C 2 -C 15 di alkyl sul famoyl ; wherein said compound exhibits high binding activity with respect to the σ receptor. 33. A compound selected from the group consisting of N- benzyl-2-phenylmorpholine, N-phenethyl-2-phenylmorpholine and N- (3-phenylpropyl )morpholine. 34. A compound of the formula R 1 R i I Cy- (CH) n -NH-X-Z wherein n is 0-5; Cy is C 3 -C 8 cycloalkyl; and R 1 is independently selected from the group consisting of hydrogen, Cι-C 6 alkyl, C n -C 6 alkoxy, fluoro, chloro, bromo, iodo and =0; R is hydrogen or Cι-C 6 alkyl; X is -(CH 2 ) q -, wherein q is 1-6; -(CH 2 ) r -C≡C-(CH 2 ) r -, wherein r is 0-3; -(CH 2 ) r -CH=CH-(CH 2 ) r -; 0 // -(CH 2 ) r -C-(CH 2 ) r -; -(CH 2 ) r -Y-(CH 2 ) r -, wherein each r is independently 0-3 and wherein Y is 0 or S; or Ci-C 8 alkyl (wherein Z is hydrogen); and Z is hydrogen, aryl or heteroaryl which may substituted by chloro, fluoro, bromo, iodo, CF 3 0,-Cg alkoxy, C 2 -C 6 dialkoxy¬ methyl, Cι-C 6 alkyl, cyano, C 3 -C 15 di alkyl ami noal kyl , carboxy, carboxamido, Cι-C 6 haloalkyl , Cι-C e haloalkylthio, ally!, aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C 6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, alkylthio, Cι-C 6 al kyl sul fonyl , hal oal kyl sul fonyl, C^C g alkyl sulfinyl , 0,-Cg hal oal kyl sulfinyl , arylthio, 0,-Cg haloalkoxy, amino, Cι-C 6 alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, C n -C e N-al kyl carbamoyl, C 2 -C 15 N,N-di alkyl carbamoyl, nitro and C 2 -C 15 di alkyl sul famoyl . 35. The compound of claim 34 selected from the group consisting of N-(3-cycl ohexyl propyl) -3-phenyl propyl amine, N- cycl ohexylmethyl -3-phenyl propyl ami ne, and N-(5- cycl ohexyl pentyl ) benzyl ami ne . 36. A compound of the formula wherein X 1 is -(CH 2 ) r -CsC-(CH 2 ) r -, wherein each r is 0-3 independently; -(CH 2 ) r -CH=CH-(CH 2 ) r -; 0 // -(CH 2 ) r -C-(CH 2 ) r -; -(CH 2 ) r -Y-(CH 2 ) r -, wherein Y is 0 or S; or C T -Cg alkyl (wherein Z is hydrogen); R 2 is independently selected from the group consisting of hydrogen, chloro, fluoro, bromo, iodo, CF 3 , Cι-C 6 alkoxy, C 2 -C β dialkoxymethyl, alkyl, cyano, C 3 -C 15 dial kyl ami noal kyl, carboxy, carboxamido, Cι-C β haloalkyl, Cι-C 6 haloalkylthio, ally!, aralkyl, C 3 -C e cycloalkyl, aroyl, aralkoxy, C 2 -C β carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 6 heterocycloalkyl, Cι-C β alkylthio, alkyl sul fonyl, Cι-C β hal oal kyl sul fonyl, Cι-C β al kyl sul f i nyl , Cι-C 6 hal oal kyl sulfinyl , arylthio, Cι-C 6 haloalkoxy, amino, Cι-C β alkyl -amino, dialkylamino, hydroxy, carbamoyl, Cι-C β N-al kyl carbamoyl , C 2 -C 15 N,N-dialkl carbamoyl, nitro and C 2 -C 15 d i alkyl sul famoyl ; V is N or CM, wherein M is hydrogen, alkyl, Cι-C 6 alkoxy, fluoro, chloro, bromo, trifluoromethyl, hydroxy or one half of a double bond with the neighboring endocyclic carbon; X is -(CH 2 ) q -, wherein q is 1-6; -(CH 2 ) r -CsC-(CH 2 ) r -, wherein r is 0-3; -(CH 2 ) r -CH=CH.-(CH 2 ) r -; 0 // -(CH 2 ) r -C-(CH 2 ) r -; -(CH 2 ) r -Y-(CH 2 ) r -, wherein each r is independently 0-3 and wherein Y is 0 or S; or C n -C β alkyl (wherein Z is hydrogen); and Z is hydrogen, aryl or heteroaryl which may be substituted by chloro, fluoro, bromo, iodo, CF 3 , C,-C β alkoxy, C 2 -C β dialkoxy¬ methyl, C τ -C 6 alkyl, cyano, C 3 -C 15 dial kyl ami noal kyl, carboxy, carboxamido, Cι-C 6 haloalkyl, Cι-C β haloalkylthio, ally!, aralkyl, C 3 -C e cycloalkyl, aroyl, aralkoxy, C 2 -C β carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C β heterocycloalkyl, Cι~C 6 alkylthio, Cι-C 6 alkyl sul fonyl, hal oal kyl sul fonyl, alkyl sulfinyl, C,-C 6 hal oal kyl sul fi nyl , arylthio, haloalkoxy, amino, alkylamino, C 2 -C 15 dialkylamino, hydroxy, carbamoyl, Cι-C 6 N-al kyl carbamoyl, C 2 -C 15 N,N-di alkyl carbamoyl, nitro and C 2 -C 15 di alkyl sul famoyl . 37. A pharmaceutical composition . comprising a therapeutically effective amount of the compound of any one of claims 17, 18, 20, 22, 23, 25, 28, 30, 32, 34 or 36 and a pharmaceutically acceptable carrier.

Inventors: GLENNON RICHARD A, GLENNON, RICHARD, A.
Applicants: UNIV VIRGINIA COMMONWEALTH, VIRGINIA COMMONWEALTH UNIVERSITY
Application year: 1990
Main classification: C07C225
IPC codes: A61K31, C07C211, C07C215, C07C217, C07C219, C07C225, C07C229, C07C233, C07C255, C07C317, C07C323, C07D207, C07D209, C07D211, C07D223, C07D239, C07D265, C07D295, C07D317, C07D471