The present invention relates to a synthesis of piperazine compounds of the formula I which exhibit neuroleptic activity and are useful in the treatment of psychosis and anxiety.
BACKGROUND OF THE INVENTION
Psychosis is a neurological condition characterised by "loss of contact with reality". Antipsychotic medications now in use have a poor safety record, especially considering that they must be taken for several years. Extrapyramidal side effects, such as akathisia, acute muscular dystonia, and tardive dyskinesia, are substantial and serious side effects of these medicines. These antipsychotics may cause dopaminergic circuits in the brain to become chronically dysfunctional over time. They can cause severe movement abnormalities such as tardive dyskinesia, tardive psychosis, and global cognitive decline, which can lead to tardive dementia.
Antipsychotics are known to relieve the symptoms of mental illnesses such as schizophrenia. Examples of such drugs include phenothiazine derivatives such as promazine, chlorpromazine, fluphenazine, thioridazine and promethazine, thioxanthenes such as chlorprothixene, butyrophenones such as haloperidol and clopasine. While these agents may be effective in the treatment of schizophrenia, virtually all except clozapine cause extrapyramidal side effects such as facial tics Since neuroleptics may be administered to a patient for years or decades, such pronounced side effects complicate recovery and further isolate the individual from society.

The following prior art is being reported:
CA2020611: Compounds of the formula and pharmaceutical compositions comprising them. The compounds are useful in the treatment of psychosis and anxiety. In the above formula, W1 is CR2R3, W2 is CR4R5, W3 is CR6R7, and one of W1, W2 and W3 may be absent, and wherein the broken line extending from W1 to W3 represents an optional double bond between either W1 and W2 or W2 and W3, in which case two of R2, R3, R4, R5, R6 and R7 are absent; and wherein X1 is hydrogen,halogen, (C1-C4)- alkyl, (C1-C4)alkoxy, nitro, cyano, trifluoromethyl, or penta- fluoroethyl, or X1 forms a heterocyclic ring with Y1; Y1 is hydrogen, (C1-C4)alkyl, phenyl or substituted phenyl, wherein said substituted phenyl is substituted with one or more substituents that are independently selected from the group consisting of halo- gen, (C1-C4)alkyl, (C1-C4)alkoxy, nitro, cyano, trifluoromethyl or pentafluoroethyl, or Y1 forms a heterocyclic ring with X1; R1 is (wherein B is selected from the group consisting of S, O and NY2; X2 is hydrogen, halogen, (C1-C4)alkyl, (C1-C4)alkoxy, nitro, cyano, trifluoromethyl or pentafluoroethyl, or X2 forms a hetero- 64680-556 cyclic ring with Y2; Y2 is hydrogen (C1-C4)alkyl, phenyl or sub- stituted phenyl, wherein said substituted phenyl is substituted with one or more substituents that are independently selected from the group consisting of halogen, (C1-C4)alkyl, (C1-C4)alkoxy, nitro, cyano, trifluoromethyl or trifluoroethyl, or Y2 forms a heterocyclic ring with X2); R2, R3, R4, R5, R6 and R7 are independently selected from the group consisting of hydrogen and lower alkyl, or any two of R2, R3, R4, R5, R6 and R7 taken to- gether with the carbon or carbons to which they are attached form a (C3-C7) saturated or unsaturated carbocyclic ring; and Z is a linear or branched (C1-C6)alkylene or a linear or branched (C2-C6)alkenylene. The Present invention sis differ from this as it involves the synthesis of derivatives of piperazine for the treatment of psychosis.
US4769366 :Pyrrolo[1,2-a]azepinone derivatives of formula: ##STR1## in which R.sub.3 is H or halogen and either (A) R is benzyl or phenylthio in which the phenyls are optionally substituted by one or more halogens or hydroxy, alkyl, alkyloxy or alkylthio radicals, R.sub.1 and R.sub.2, which may be identical or different, denote alkyl optionally substituted by dialkylamino in which the alkyls are optionally joined to form a 1-pyrrolidinyl, piperidino, morpholino or 1-piperazinyl ring substituted by alkyl, or alternatively R.sub.1 and R.sub.2 form a heterocyclic ring chosen from pyrrolidine, piperidine, morpholine and piperazine, substituted by alkyl, alkenyl (2 to 4 C), benzyl or phenethyl optionally substituted by halogen, alkyl, alkyloxy, alkylthio, CF.sub.3, COOH, carboxyalkyl, alkyloxycarbonyl, alkyloxycarbonylalkyl, hydroxyalkyl, or alkylcarbonyloxyalkyl in which the alkylcarbonyl has 2 to 18 C, PA0 or (B) R is phenyl optionally substituted with one or more halogens or hydroxy, alkyl, alkyloxy or alkylthio radicals and R.sub.1 and R.sub.2 together form a piperazine or homopiperazine ring substituted by hydroxyalkyl (2 to 4 C), alkenyl (2 to 4 C), alkynyl (2 to 4 C), benzyl or phenethyl optionally substituted by halogen, alkyl, alkyloxy, alkylthio, CN, CF.sub.3, COOH, carboxyalkyl, alkyloxycarbonyl, alkyloxycarbonylalkyl, hydroxyalkyl, or alkylcarbonyloxyalkyl in which the alkylcarbonyl has 2 to 18 C, the said alkyls containing, except where otherwise stated, 1 to 4 C in a straight or branched chain, PAL and the pharmaceutically acceptable salts thereof, PAL are useful as antipsychotics. The Present invention sis differ from this as it involves the synthesis of derivatives of piperazine, which has neuroleptic activity and are usefull in the treatment of psychosis.
RU02123001 : The organic chemistry, pharmacology. SUBSTANCE: invention relates to oxides of 4-phenylpiperazines and 4-phenylpiperidines of the general formula (I) where R1 is C1-8-alkoxy; R2 is hydrogen or methyl; A is N, CH or N+-O-; B means N or N+-O- at condition that when A means N or CH then B must be N, or their pharmaceutically acceptable salts. The synthesized compounds show significant activity in mammals and neuroleptic and antipsychotic effects in human. The Present invention sis differ from this as it involves the synthesis of derivatives of piperazine, which has neuroleptic activity and are usefull in the treatment of psychosis.
OBJECTS OF THE INVENTION
Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows.
It is an object of the present disclosure to ameliorate one or more problems of the prior art or to at least provide a useful alternative

An object of the present disclosure is to provide the synthesis of phenyl piperazine derivatives.

Another object of the present disclosure is to synthesis the compounds the with high purity.

Still another object of the present disclosure is to provide that the synthesis involves simple reaction.

Still another object of the present disclosure is to provide that the reaction involves improved method of synthesis.

Still another object of the present disclosure is to provide that the synthesizes compounds showed the enhanced effectiveness.

Other objects and advantages of the present disclosure will be more apparent from the following description, which is not intended to limit the scope of the present disclosure.

SUMMARY OF THE INVENTION
The following presents a simplified summary of the invention in order to provide a basic understanding of some aspects of the invention. This summary is not an extensive overview of the present invention. It is not intended to identify the key/critical elements of the invention or to delineate the scope of the invention. Its sole purpose is to present some concept of the invention in a simplified form as a prelude to a more detailed description of the invention presented later.

The present invention is generally directed to the synthesis of compound with general formulae I

Another embodiment of the invention is the synthesized compound is characterized by using IR, H1NMR, and Mass spectroscopy.

An embodiment of the present invention is the compound of general formulae I is potent neuroliptic agents that can be used in the treatment of psychotic conditions such as schizophrenia.

Another embodiment of the invention is the compound of general formulae I may also be used in the treatment of other disorders of the central nervous system such as anxiety and aggression.

DETAILED DESCRIPTION OF THE INVENTION
The following description is of exemplary embodiments only and is not intended to limit the scope, applicability or configuration of the invention in any way. Rather, the following description provides a convenient illustration for implementing exemplary embodiments of the invention. Various changes to the described embodiments may be made in the function and arrangement of the elements described without departing from the scope of the invention.
EXAMPLE 1: Synthesis Of Phenylpiperazine Derivatives
Phenylpiperazine (0.005 mol)and 1-(4-(2-chloroethoxy) phenyl) ethanone (0.005 mol) wasdissolved in acetonitrile (100 ml) in a two necked round bottom flask. Anhydrous potassium carbonate (0.010 mol) and catalytic amount of potassium iodide was added into the solution. The reaction mixture was refluxed for 24 hours with continuous stirring on a heating magnetic stirrer. The reaction mixture was filtered and solvent removed under vacuum distillation. The obtained compound was washed with water, dried and recrystallized from ethanol to obtain the 1-(4-(2-(4-phenylpiperazin-1-yl) ethoxy) phenyl) ethanone.

EXAMPLE 2: Characterization of 1-(4-(2-(4-phenylpiperazin-1-yl) ethoxy) phenyl) ethanone
IR ( KBr, cm-1): 3058, 2927, 1678, 1589, 1358,1276,1044. 1H NMR (300 MHz; CDCl3 d): 2.69-2.86 (8H, pip ring); 3.39(2H, CH2N);3.87 (3H,COCH3); 4.04 (2H, OCH2); 6.77 -7.25(9H, Ar-H); MS(ESI)m/z:325.2;Mp: 68-700C; Yield: 80 %;Rf value : 0.50 (n-hexane: ethyl acetate; 1:2)
EXAMPLE 3: Antipsychotic Activity
The compound 1-(4-(2-(4-phenylpiperazin-1-yl) ethoxy) phenyl) ethanone was subjected to antipsychotic activity by inhibition of 5-HTP induced head twitches behavior and induction of catalepsy studies in Swiss albino mice. Compound 1-(4-(2-(4-phenylpiperazin-1-yl) ethoxy) phenyl) ethanone was showedpotent inhibition of 5HTP induced head twitches behavior at 20 mg/kg dose and low induction of catalepsy at 80 mg/kg dose in Swiss albino mice as compare with standard drug.
While considerable emphasis has been placed herein on the specific features of the preferred embodiment, it will be appreciated that many additional features can be added and that many changes can be made in the preferred embodiment without departing from the principles of the disclosure. These and other changes in the preferred embodiment of the disclosure will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the disclosure and not as a limitation.

We Claim,

1. A Compound of general formulae I,

2. The compound of general formulae I, as claimed in claim 1, exhibited neuroleptic activity.
3. The compound of general formulae I, as claimed in claim 1, is useful in the treatment of psychosis and anxiety.