PRODRUGS OF COMPOUNDS WITH NH-ACIDS

Abstract

Claim 1: A compound characterized in that it has the formula (1), wherein R¹ is selected from -C(RA)(RB)-OC(O)OR²⁰, -C(RA)(RB)-OC(O)R²⁰, -C(RA)(RB)-OC(O)NR²⁰R²¹, wherein each RA and RB is independently selected from hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; R²⁰ is selected from C₇₋₂₄ alkyl, C₇₋₂₄ alkenyl, C₇₋₂₄ alkynyl; R²¹ is selected from hydrogen, aliphatic, substituted aliphatic, aryl or substituted aryl; yw is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11.

Description

This application invokes the benefit of U.S. Provisional Applications Nos. 61 / 220.480, filed June 25, 2009; 61 / 293.087, filed January 7, 2010; and 61 / 293.133, filed January 7, 2010. The full descriptions of which are incorporated herein by reference. BACKGROUND OF THE INVENTION (i) Field of the invention. The present invention relates to prodrugs of lactam, amide, imide, sulfonamide, carbamate, urea, benzamide, and acylaniline containing pharmacophores. (i) Background of the invention. Drug delivery systems are often critical for the safe and effective administration of a biologically active agent. Perhaps the importance of such systems is best appreciated when considering patient compliance and consistent dosing. For example, reducing the dosing requirement of a drug from four times daily to a single daily dose could have significant value in terms of ensuring patient compliance and optimizing therapy. Optimizing drug bioavailability has many potential benefits. For patient convenience and to generally increase compliance, less frequent dosing is recognized as desirable. By extending the period during which the drug is released, a longer duration of action per dose is expected. This will allow for... A comprehensive improvement in dosing parameters would be achieved, such as taking a drug once a day where previously four doses per day were required, or once a week or even less frequently where daily dosing was previously necessary. Currently, many drugs are dosed once a day, but not all of them possess pharmacokinetic properties suitable for dosing intervals of exactly 24 hours. Extending the period during which these drugs are released would also be beneficial. One of the fundamental considerations in drug therapy relates to the relationship between blood levels and therapeutic activity. For most drugs, it is of primary importance that serum levels remain between a minimally effective concentration and a potentially toxic level. In pharmacokinetic terms, the peaks and troughs of drug blood levels ideally fall within the therapeutic serum concentration range. For certain therapeutic agents, this range is so narrow that dosage control becomes critical. In an attempt to address the need for improved bioavailability, various technologies have been developed to modulate drug release. For example, poorly soluble 5,5-diphenylimidazolidine-2,4-diones have been derivatized to give phosphate ester prodrugs to improve solubility (Stella et al., U.S. Patent No. 4,260,769, 1981). Enteric coatings have been used to protect pharmaceuticals in the stomach, and microencapsulation of active agents using proteinaceous microspheres, liposomes, or polysaccharides has been effective. to reduce enzymatic degradation of the active agent. Enzyme-inhibiting adjuvants have also been used to prevent enzymatic degradation. There is a wide range of pharmaceutical formulations that provide sustained release through microencapsulation of the active agent in dicarboxylic acid amides, modified amino acids, or thermally condensed amino acids. Slow-release additives can also be intermixed with a variety of active agents in tablet formulations. Although microencapsulation and enteric coating technologies confer greater stability and sustained-release properties to active substances, these technologies suffer from several disadvantages. The incorporation of the active agent is often dependent on diffusion within the microencapsulation matrix, which may not be quantitative and can complicate dosage reproducibility. Furthermore, encapsulated drugs depend on diffusion out of the matrix, matrix degradation, or both, which is highly dependent on the chemical properties and water solubility of the active agent. Conversely, water-soluble microspheres swell to an infinite degree and, unfortunately, can release the active agent in bursts, leaving a limited amount available for sustained release.Furthermore, in some technologies, the control of the degradation process necessary for the release of the active agent is unreliable. For example, since the release of the active agent from enterically coated active agents depends on pH, and pH and residence time vary, the... The release speed is difficult to control. The binding of polypeptides to drugs has been used in various implantable drug delivery systems. Additionally, other large polymeric vehicles that incorporate drugs into their matrices are used as implants for gradual drug release. Yet another technology combines the advantages of covalent drug binding with the formation of liposomes, where the active ingredient is attached to highly ordered lipid films. However, there is still a need for an active agent delivery system that is capable of administering certain active agents that, until now, have not been formulated or were difficult to formulate in a sustained-release formulation to be released in a sustained manner over a period of time and that is convenient for dosing the patient. In general, there is a recognized need for sustained drug administration that reduces the daily dosing requirement and allows for controlled and sustained release of the source drug, while also avoiding release irregularities and bulky formulations encountered with typical controlled dissolution sustained-release methods. SUMMARY OF THE INVENTION The present invention achieves this by extending the period during which a drug of source containing lactam, amide, imide, sulfonamide, carbamate, urea, benzamide, acylainine, and cyclic amide is released and absorbed after administration to the patient, providing a duration of the longer duration of action per dose than the parent drug itself. In one embodiment, the compounds suitable for use in the methods of the invention are parent drug derivatives containing lactam, amide, imide, sulfonamide, carbamate, urea, benzamide, acylaniline, and cyclic amide, which are substituted at the amide nitrogen or oxygen atom with labile prodrug units attached to the aldehyde. Preferably, the prodrug units are hydrophobic and reduce the polarity and solubility of the parent drug under physiological conditions. In one embodiment, the invention provides a prodrug compound of Formula I, II or III: YOUR \ B \ Formula II Formula III Formula I and geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof; wherein A and B together with the -N(C=X)- or -N=CX- or -S(O)2-N- group to which they are bound form a parent drug; X is -S- or -O-; We select between -C(Ra)(Rb)-OR20, -C(Ra)(Rb)-OC(0)OR-2o, -C(Ra)(Rb)OC(O)R20, -C(Ra)(Rb)-OC(O)NR-20R2i, -(C(Ra)(Rb))-O -(C(Ra)(Rb))OP(O)(OR20)(OR21), -[C(Ra)(Rb)O]z-R20, -[C(Ra)(Rb)O]zC(O)OR-20, [C(Ra)(Rb)O]zC(O)R20, -[C(Ra)(Rb)O]zC(O)NR-20R21,-[C(Ra)(Rb)O]z-OPO3MY -[C(Ra)(Rb)O]zP(O)2(OR20)M y-[C(RA)(RB)O]zP(O)(OR20)(OR2i); where z is 2 or 3; where each Ra and Rb is independently selected from hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; each R20 and R21 is independently selected from hydrogen, aliphatic, substituted aliphatic, aryl or substituted aryl; Y and M are either the same or different and each is a monovalent cation; or M and Y together are a divalent cation, and where said parent drug contains a 5,5 diphenylimidazolidin2,4-dione portion of Formula I, R1 is not -CH(Ra)OPO3MY, CH(Ra)OP(O)(OH)2, or CH(Ra)OC(O)R20. The invention also provides a method for sustained administration of a source drug by administering a conjugate of the source drug with a labile unit, wherein the conjugate is represented by Formula I, II or III. BRIEF DESCRIPTION OF THE FIGURES The foregoing objects, features, and advantages of the invention, and others, will become evident from the following more detailed description of preferred embodiments of the invention, as illustrated in the accompanying figures, in which identical reference characters refer to the same parts through all the different views. The figures are not necessarily to scale; rather, the emphasis has been placed on illustrating the principles of the invention. Figure 1: PXRD Spectrum of Compound 7 Figure 2: IR Spectrum of Compound 7 Figure 3: Raman Spectrum of Compound 7 Figure 4: TGA thermogram spectrum of Compound 7 Figure 5: DSC Thermogram of Compound 7 Φ Figure 6: Pharmacodynamic (PD) study of Compound 4 in an AMPH-induced locomotion model. Figure 7: Pharmacodynamic (PD) study of Compound 7 in an AMPH-induced locomotion model. Figure 8: Plasma concentration of aripiprazole after intravenous administration of (0.5 mg / Kg) of Compound 7 to rats. Figure 9: Plasma concentration of aripiprazole, dehydroarylpiprazole and Compound 7 after intramuscular administration of 30 mg / kg of Compound 7 to dogs. Figure 10: Pharmacokinetic profile of pioglitazone, Compound 1002 and Compound 1008 after intravenous administration (equivalent to 20 mg of pioglitazone) to rats. DETAILED DESCRIPTION OF THE INVENTION One aspect of the present invention provides a compound of general formula I, II or III: TO \ N---R, \ Formula II Formula III Formula I or the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof; wherein A and B together with the -N(C=X)- or -N=CX- or -S(O)2-N- to which they are attached form a parent drug; X is -S- or -O-; Ri is selected between -C(Ra)(Rb)-OR20, -C(Ra)(Rb)-OC(0)OR-2o> -C(Ra)(Rb)8 Φ OC(O)R20, -C(Ra)(Rb)-OC(O)NR-20R2i, -(C(Ra)(Rb))-OPO3MY, -(C(Ra)(Rb))OP(O)(OR20)(OR21), -[C(Ra)(Rb)O]z-R20, -[C(Ra)(Rb)O]zC(O)OR-20, [C(Ra)(Rb)0]zC(0)R2o, -[C(Ra)(Rb)0]zC(0)NR-2oR2i, -[C(Ra)(RB)O]Z-OPO3MY, -[C(Ra)(Rb)0]zP(0)2(OR2o)M y-[C(RA)(RB)0]zP(0)(OR2o)(OR2i); wherein each RAand Rbse selects in an independent manner from among hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; each R20 and R21 is independently selected from hydrogen, aliphatic, aliphatic substituted, aryl or aryl substituted; Y and M are the same or different and each is a monovalent cation; or M and Y together are a divalent cation; and where said parent drug contains a 5,5 diphenylimidazolidin-2,4-dione portion of Formula I, Rt is not -CH(RA)OPO3MY, CH(Ra)OP(O)(OH)2, or -CH(Ra)OC(O)R20. In one embodiment, the compounds of the invention with Formulas I, II, and III are less soluble, and preferably less soluble by at least an order of magnitude, compared to the parent drug from which they were derived. In one embodiment, the prodrugs of Formulas I, II, and III have a water solubility of less than approximately 0.5 mg / ml, preferably less than approximately 0.1 mg / ml, preferably less than approximately 0.01 mg / ml, preferably less than approximately 0.001 mg / ml, preferably less than approximately 0.0001 mg / ml, and even more preferably less than approximately 0.00001 mg / ml when solubility is measured in a phosphate buffer solution (pH 7.4) at room temperature. In a preferred embodiment, a compound of the invention provides The sustained delivery of the source drug for hours, days, weeks, or months when administered to a subject, for example, orally or parenterally. For example, the compounds may provide sustained delivery of the source drug for at least 8, 12, 24, 36, or 48 hours, or at least 4, 7, 15, 30, 60, 75, or 90 days, or for longer. Without being bound by any theory, it is believed that the compounds of the invention form an insoluble deposit after parenteral administration, for example, subcutaneous, intramuscular, or intraperitoneal injection. In one embodiment, a prodrug of the invention may also comprise a sustained-release delivery system to provide the prodrug with additional protection from enzymatic or chemical degradation. In another embodiment, the invention provides a method for the sustained administration of a source drug containing a lactam, amide, imide, sulfonamide, carbamate, urea, benzamide, or acylaniline to a subject in need. Each of these groups comprises an amide NH group. The method comprises administering to the subject an effective amount of a prodrug formed by substituting a labile, hydrophobic prodrug unit attached to the aldehyde in the NH group. The prodrug has reduced solubility under physiological conditions compared to the source drug and, after administration, provides longer sustained therapeutic levels than the levels of the source drug observed after administration of the source drug.In a preferred embodiment, the amide NH group has a pKa of between approximately 5 and approximately 22, preferably between approximately 5 and approximately 21, and preferably between approximately 5 and approximately 20. In a preferred embodiment, Ri is selected from Table-1. EITHER Or either either EITHER Yo EITHER ®O-CL=O 00-0.=0 II ωο ®ο )13 >>5 ) 23 Ο \ / θγθ^χ ο \ / θγ·θ\χ\ θ^A X In a more preferred embodiment, Ri is selected from Table 2 In a more preferred embodiment, Rj is selected from Table 3. Table 30 / —1 N \ In a more preferred embodiment, Ri is selected from Table 4. Table 4 °χ>\ θχ / Χ ο OA either θχ^ζ'θ\ζ-'Χ <KL o °χA <Χλ θχA °A o0 LACTAM, CYCLIC UREA, IMIDE AND CARBAMATE PRODRUGS CONTAINING PHARMACOPHORES In one embodiment, the compounds of the present invention are represented by Formula IV or V as illustrated below, or the geometric isomers, enantiomers, diastereomers, racemates, co-crystals Formula IV Formula V where it represents a single or double union; X and Ri are as defined above; Each Χι, X2, and where v is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; where each R10 and R11 independently is absent or is hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; alternatively, two R-10 and Rn together with the atoms to which they are attached can form an optionally additional substituted 3, 4, 5, 6 or 7-membered ring; yt is 0, 1, 2 or 3. In one embodiment, the compounds of the present invention are represented by Formula VI or Vil as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, salts pharmaceutically acceptable and solvates thereof: Formula VI Formula Vil where it represents a single or double union; X, Xi, X2 and Ri are as defined above; The Y ring is an optionally substituted cycloalkyl, cycloalkenyl, heterocyclyl or aryl ring containing one, two or three rings; each Fi and F2 independently is absent or selected from R5-ACyi-BD-; where, A is absent or selected from optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, -S-, -O-, -S(O)-, -S(O)2-, -S[C(R3o)(R3i)]u-, S(0)[C(R3o)(R3i)]u-, -S(0)2[C(R30)(R31)]u-,-0[C(R3o)(R3i)]u-, -N(R-30)-, N(R30)[C(R31)(R32)L-, -[C(R3o)(R3i)]u,-C(0)[C(R3o)(R3i)]u-; where each u is independently 1, 2, 3, 4, 5, 6 or 7; Cyi is absent or is optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocyclo, optionally substituted aryl or optionally substituted heteroaryl; B is absent, or is a ligand; D is absent or selected from -O-, -NR33, -C(R34)( R3s)-, -S-, S(O)-, -S(O)2-, and C(O)-; Each Gi and G2 independently is absent or selected from -S-, -O-, -S(O)-, -S(O)2-, -SC(R4o)(R4i)-, -S(O) C(R40)(R4i)->-S(0)2C(R4o)(R4i), -C(O)-, -C(OR4o)(R4i)-, -OC(R4o)(R4i)-, -N(R-4o)-, -C(R4o)=C(R4i)-, -N(R4o)C(R4i)(R42)_, and -[C(R4o)(R4i)]u-, Each R-3, R4, Rs, R3o> R31, R32 R33, R34> R35, R40. Rn> and R42 independently is absent or selected from hydrogen, halogen, -OR10, SR10, -NR10-R11-, -C(0)Rio, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocycle; Alternatively, two R3 groups or two R4 groups or one R3 group with one R4 group together with the atoms to which they are attached and the atoms involved form an optionally substituted ring; myq are selected independently from 0, 1, and 2. In a preferred embodiment, G2 is selected from -N- or -C(Ri0)-. In a preferred embodiment, the R5 portion is an aryl or heteroaryl group selected from: v / WWU JWV\> ιΛ / Wb where R1Oo and R101 each have 1 to 4 substituents independently selected from hydrogen, halogen, optionally substituted C2-C8 alkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C3-C8 alkoxy, optionally substituted C3-C8 alkylamino, and optionally substituted C3-C8 aryl; and, R103 is selected from hydrogen, halogen, optionally substituted C2-C8 alkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C3-C8 alkoxy, and optionally substituted C3-C8 alkylamino. optionally substituted alkylamino and optionally substituted Ci-Cs aryl. In a preferred embodiment, Cy1 is selected from: In a preferred embodiment, the bivalent B is a direct bond, a CiC10 alkyl, C1-C10 alkenyl, C1-C10 alkynyl, C1-C10 alkoxy, alkoxyC-i-C10 alkoxy, CrC10 alkylamino, alkoxyCi-Ci-Ci-alkylamino, C1-C10 alkylcarbonylamino, C1-C10 alkylaminocarbonyl, aryloxyC-iC-ioalkoxy, aryloxyCrCi-Ci-alkylamino, aryloxyC-iC-io alkylaminocarbonyl, Ci-Ci-alkylaminoalkylaminocarbonyl, CrCi-alkyl(N-alkyl)aminoalkyl-aminocarbonyl, alkylaminoalkylamino, alkylcarbonylaminoalkylamino, alkyl(N-alkyl)aminoalkylamino, (N-alkyl)alkylcarbonylaminoalkylamino, alkylaminoalkyl, alkylaminoalkylaminoalkyl, alkylpiperazinoalkyl, piperazinoalkyl, alkylpiperazino, alkenylaryloxyCi-C1Oalkoxy, alkenylarylaminoCi-Ci0alkoxy, alkenylarylalkylaminoCi-Ci-Ci-alkoxy, alkenylaryloxyC-iC-ioalkylamino, alkenylaryloxyCrC10alkylaminocarbonyl, piperazinoalkylaryl, heteroarylCrC10alkyl, heteroarylC2-C10alkenyl, heteroarylC2-C10alkynyl, heteroarylC2C10ioalkylamino, heteroarylCrC10alkoxy, heteroaryloxyC2-C10alkyl, heteroaryloxyC2-C10alkenyl, heteroaryloxyC2-C10alkynyl,linear chain heteroaryloxyCrCioalkylamino or heteroaryloxyCrCioalkoxy., In one embodiment, the compounds of the present invention are represented by Formula VIII or VIIIA as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: where the ring Y, R1, R3, R4, G1, G2, X, F2, and myq are as defined above. In a more preferred embodiment, the compounds of the present invention are represented by Formula IX or X as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: Formula IX Formula X where Ri, R3, F2, and q are as defined above. In a preferred embodiment, a compound is selected from Table IX-X. A more preferred embodiment is a compound from Table IX-X where R-ι is selected from Tables 1-4. Table IX-X In a more preferred embodiment, domperidone prodrugs are disclosed. (Formulas 4 and 11 of Table IX-X). A more preferred embodiment is a compound of Formula 4 of Table IX-X, where Ri is selected from Table 1. In a more preferred embodiment, a compound of Formula 4 of Table IX-X is disclosed, where Ri is selected from Tables 2-4. In a more preferred embodiment, droperidol prodrugs are revealed. (Formulas 6 and 13, of Table IX-X). In a more preferred embodiment, a compound of Formula 6 of Table IX-X is disclosed where Ri is selected from Table 1. A more preferred embodiment is a compound of Formula 6 of Table IX-X where Ri is selected from Tables 2-4. In a more preferred embodiment, pimozide prodrugs are disclosed. (Formulas 7 and 14 of Table IX-X). In a more preferred embodiment, a compound of Formula 7 of Table IX-X is disclosed, where Ri is selected from Table 1. In a more preferred embodiment, a compound of Formula 7 of Table IX-X is disclosed, where Ri is selected from Tables 2-4. In another embodiment, the compounds of the present invention are represented by Formula XI or XII as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: Formula XI Formula XII where the ring Y, R-ι, R3, R4, X, F1(G1, G2, m and q are as defined above. In another embodiment, the compounds of the present invention are represented by Formula XIA or XIIA as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: Formula ΧΙΑ Formula XIΙΑ where Ri, R3, R4, R5, R10, R11, A, D, m, and q are as defined above; R-2 is absent or selected from hydrogen, halogen, -OR10, -SR10, NR10-R11-, optionally substituted aliphatic, optionally substituted aryl or optionally substituted aryl or heterocycle; r is 0,1,2, 3, 4, 5, 6, 7, 8, 9,10 or 11; each G3 and G4 are selected independently from -N-, and -C(Rio)[C(Rio)(Rn)]a-, where a is 0, 1 or 2; X-20 is -C(Rio)- or -N-; yp is 0, 1, 2 or 3. In another embodiment, the compounds of the present invention are represented by Formula XIB or XIIB as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof Formula XIB Formula XI IB where Ri, R2, R3, R*, R5, R10, R11, A, D, m, p and q are as defined above. In another embodiment, the compounds of the present invention are represented by Formula XIC or XIIC as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: Formula XIC Formula XIIC where R-ι, is as defined above; yw is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11. In another embodiment, the compounds of the present invention are represented by Formula XID or XIID as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: Formula XID Formula XIID where, X1, R1, R2, R3, R5, A, B, D, G3, G4, p, q, R10 and Rn are as defined above. In another embodiment, the compounds of the present invention are represented by Formula XIE or XIIE as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: Formula XIE Formula XIIE where X, Ri, R2, R3· R® A, D, G3, G4, m, q, r, R10 and Rn are as defined above. In another embodiment, the compounds of the present invention are represented by Formula XIF or XIIF as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: Formula XIF Formula XIIF where, X, R1, R2, D, r, R10 and Rn are as defined above. In another embodiment, the compounds of the present invention are represented by Formula XIG or XIIG as illustrated below, or the geometric isomers, enantiomers, diastereomers, racemates, salts pharmaceutically acceptable and solvates thereof: Formula XIG Formula XIIG where Ri, is as defined above. In another embodiment, the compounds of the present invention are represented by Formula XIH or XIIH as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: Formula XIH Formula XIIH where, X, Ri, R2, R5, A, D, G3, G4 and p, are as defined above. In another embodiment, the compounds of the present invention are represented by Formula Xl-I or Xil-l as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: where Ri, is as previously defined. In another embodiment, the compounds of the present invention are represented by Formula XIJ or XIIJ as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: Formula XIJ Formula XIIJ where X, Ri, R2, R3, R4, R5, A, D, G3, G4, p, R10 and R11 are as defined above. In another embodiment, the compounds of the present invention are represented by Formula XIK or XIIK as illustrated below, or the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: Formula XIK Formula XIIK where R-ι, is as defined above. In a preferred embodiment, a compound is selected from the Tables XI-XII. A more preferred embodiment is a composite of Tables XI- XII where Ri is selected from Tables 1-4. Ri In a more preferred embodiment, aripiprazole prodrugs are disclosed (Formula 1 and 7 of Tables XI-XII). In a more preferred embodiment, a compound of Formula 1 is disclosed, where Ri is selected from Table 1. In a more preferred embodiment, a compound of Formula 1 is disclosed, where Ri is selected from Tables 2-4. In a more preferred embodiment, dehydroaripiprazole prodrugs are disclosed (Formulas 2 and 8 of Tables XI-XII). In a more preferred embodiment, a compound of Formula 2 is disclosed, where Ri is selected from Table 1. In a more preferred embodiment, a compound of Formula 2 is disclosed, where Ri is selected from Tables 2-4. In a more preferred embodiment, ziprasidone prodrugs are disclosed (Formulas 3 and 9 of Tables XI-XII). In a more preferred embodiment, a compound of Formula 3 is disclosed, where Rt is selected from Table 1. In a more preferred embodiment, a compound of Formula 3 is disclosed, where Ri is selected from Tables 2-4. In a more preferred embodiment, bifeprunox prodrugs are disclosed (Formulas 4 and 11 of Tables XI-XII). In a more preferred embodiment, a compound of Formula 4 is disclosed, where Ri is selected from Table 1. A more preferred embodiment reveals a compound of Formula 4 where Ri is selected from Tables 2-4. Representative compounds according to the invention are those selected from Tables A-I below and their geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates: Table A No Structure No Structure H2N O either O o / \ either Table B No Structure 150 151 either 231 o No. Structure 760 r<Ω \O o. i LL IX IX co i either <N in Ί ho O) Compounds of formula IX, X, XI, XII and in particular compounds of AD tables are useful for the treatment of neurological and psychiatric disorders including schizophrenia, mania, anxiety, and bipolar disorder. These compounds provide sustained release of parent pharmacophores by cleaving the labile portion, Ri. As such, compounds of formula IX, X, XI, XII and in particular the compounds in Tables AD are useful for the treatment of neurological disorders by providing sustained release of parent drugs. In another embodiment, the compounds of the present invention are represented by Formula XIII or XIV as illustrated below, or the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: Formula XIII Formula XIV where R1Oo, R101, R102, and R103 are independently selected from absent, hydrogen, halogen, -OR10, -SR10, -NR10-R11-, optionally substituted aliphatic, optionally substituted aryl, or optionally substituted aryl or heterocycle; Alternatively, two R100 and R101 together with the atoms to which they are attached and the atoms involved form an optionally substituted ring; and 121 φ Χ-ιοο is -CH- or -N-. A preferred embodiment is a compound selected from Table XIII-XIV. A more preferred embodiment is a compound from Table XIII-XIV where R-ι is selected from Tables 1-4. 122 123 124 ACYLANILINE PRODRUGS In another embodiment, the compounds of the present invention are represented by Formula XV or XVI as illustrated below, or the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: where Ri is as defined above; Each R5o, R-51, R52· R53, R54 and R55 is independently selected from hydrogen, halogen, -OR10, -SR10, -NR10-R11-, optionally substituted aliphatic, optionally substituted aryl or optionally substituted aryl or heterocycle; Yo 125 Alternatively, two or more R5o, R-51, R52, Rs3> R54 and R55 together with the atoms to which they are attached form an optionally substituted ring. A preferred embodiment is a compound selected from Table XV-XVI. A more preferred embodiment is a composite of Table XV-XVI where R1 is selected from Tables 1-4. 126 127 128 EITHER 129 130 φ Thiazolidinones In another embodiment, the compounds of the present invention are represented by Formula XVII, XVIII or XIX as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: 131 Formula XVII Formula XVIII Formula XIX where Fi and Rí are as defined above. A preferred embodiment is a compound of Formula XX, XXI or XXII as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates of where Ri is as defined above; Cy2 is an optionally substituted heterocyclic ring; and X5está ausente o se selecciona entre -S-, -O-, -S(O)-, -S(O)2-, -N(R10)-, -C(O), -CÍORwXRn)-, -[CÍRwXRuMv-.-OtCÍRwXRuMv-.-OlCÍRioXRiiMvO-, 132 S[C(R10)(Rn)]vO-, -NR12[C(R10)(Rii)]vO-, -NRi2[C(Ri0)(Rh)]vS-, S[C(Rw)(Rii)]v-, -C(O)[C(R10)(Rii)]v-, andC(RiO)=C(Rio)-; where you see 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. A preferred embodiment is a compound of Formula XXIV as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts, and solvates of In a more preferred realization of Formula XXIV, Ri is selected from Tables 1-4. A preferred embodiment is a compound of Formula XXIV as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: In a more preferred embodiment of Formula XXV, Ri is selected from Tables 1-4. 133 A preferred embodiment is a compound of Formula XXVI as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates of Formula XXVI In a more preferred embodiment of Formula XXVI, one is selected from Tables 1-4. A preferred embodiment is a compound of Formula XXVII as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts, and solvates of Formula XXVII In a more preferred embodiment of Formula XXVII, Ri is selected from tables 1-4. A preferred embodiment is a compound of Formula XXVIII as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts, and solvates of 134 the same: Formula XXVIII In a more preferred embodiment of Formula XXVIII, Ri is selected from Tables 1-4. A preferred embodiment is a compound of Formula XXIV as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: Formula XXIX In a more preferred embodiment of Formula XXIX, Rt is selected from Tables 1-4. A preferred embodiment is a compound of Formula XXIV as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: 135 In a more preferred embodiment of Formula XXX, Ri is selected from Table 1. A preferred embodiment is a compound of Formula XXXI as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: Formula XXXI In a more preferred embodiment of Formula XXXI, R! is selected from Table 1. A preferred embodiment is a compound of Formula XXXII as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: 136 In a more preferred embodiment of Formula XXXII, Ri is selected from Table 1. In a preferred embodiment, a compound of Formula XX-XXII is selected from Table XX-XXII below, where Ri is as described above. A more preferred embodiment is a compound from Table XX-XXII where Ri is selected from Tables 1-4. Table XX-XXII 137 aw-fíSitWáiif •N \ EITHER EITHER 138 Thiazolidinedione prodrugs of Formula XVII to XXXII are useful for the treatment of type 2 diabetes mellitus. A method of treating type 2 diabetes mellitus by administering a prodrug of Formula XVII to XXXII, specifically a compound from Table XX-XXII above, is provided herein, where the prodrug provides sustained release of the parent drug. The parent drug results from the cleavage of the labile Ri portion. In some embodiments, a compound of Formula XXVII is selected from Table G: 139 i Table G No. Structure Yo 140 Yo 142 Table H No Structure No Structure ,either 143 Ί P 145 146 147 OH 148 Table I No Structure No Structure 149 EITHER 150 151 o152 153 154 155 156 BARBITURATES In another embodiment, the compounds of the present invention are represented by Formula XXXIII-XXXVII as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: R100R1R1 Formula XXXV Formula XXXIII Formula XXXIV Formula XXXVII Formula XXXVI where, X, ΧΊ, X2, R100. R101. and R1 are as defined above; X10 is -S or -O. In a preferred embodiment, a compound from Tables XXXIII-XXXVII is provided. A more preferred embodiment is a compound from Tables XXXIII-XXXVII where R1 is selected from Tables 1-4. TABLE XXXIII-XXXIV 157 158 Pyridone prodrugs, pyrimidione and pyrimidione In another embodiment, the compounds of the present invention are represented by Formula XXXVIII or XXXIX as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: 159 Formula XXXVIII Formula XXXIX where X, R-ι, R3, R4, m and q are as defined above; X11 is-N- or -C(R10)-; X12 is -C(O)-, -C(S)-, -C(R10)(Ru)- or -C(R10)(ORn)-; and X13 is —O, -S, -N(Rio)(Ru), -OR10. A preferred embodiment is a compound selected from the Tables XXXVII-XXXIX. A more preferred embodiment is a composite of the Tables XXXVIII-XXXVIX where R1 is selected from Tables 1-4. TABLE XXXVIII h2n. •R, NC. 160 EITHER S' N' EITHER 161 PHARMACOPHORES OF BENZAMIDE PRODRUGS In another embodiment, the compounds of the present invention are represented by Formula XL or XLI as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: 162 FORMULA XLI where Ri, R50, R-51, R52, R53, R54 and R55 are as defined above. XL-XLI Table 163 164 EITHER 165 166 IMIDE PRODRUGS PHARMACOPHORES In another embodiment, the compounds of the present invention are represented by Formula XLII, XLIII or XLIV as illustrated below, and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: \6Ί R100 FORMULA XLII FORMULA XLIII FORMULA XLIV where Ri R-iooo, R101, X, Xi and X2 are as defined above; alternatively R1Oo and R101 together with the atoms to which they are attached form a ring of 3, 4, 5, 6 or 7 members. A preferred embodiment is a compound selected from the Tables XLII-XLIV. A more preferred embodiment is a composite of the Tables XLII-XLIV where R1 is selected from Tables 1-4. Tables XLII-XLIV XLIIXLIIIXLIV- either Oh Ό OH' 168 169 ο· 170 In another embodiment, the compounds of the present invention of the Formulas IV-VII are selected from Tables IV-VII. OH Tables IV–VII OH 171 Ri OH Oh 172 173 174 Oh 175 PHARMACOPHORES OF SULFONAMIDE PRODUCES In another embodiment, the compounds of the present invention are represented by Formula III as illustrated below, or their 176 geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: Oo II / ' A--SN EITHER Formula III A preferred embodiment is a compound selected from those in Table III. A more preferred embodiment is a compound from Table III where Ri is selected from those in Tables 1-4. Table III 177 -EITHER 178 'N' 179 to 180 181 either Yo 182 Yo 183 Yo. 184 Chlorothiazide and hydrochlorothiazide compounds of formula III, and in particular those listed in Table III, are useful for the treatment of hypertension, congestive heart failure, osteoporosis, symptomatic edema, peripheral edema, kidney stones, diabetes, nephrogenic diabetes insipidus, hypercalcemia, Dent's disease, and Meniere's disease. The compounds of formula III and those listed in Table III provide sustained release of the source drugs by cleavage of the labile Ri unit. Compounds of formula III, for example, III-63 to III-71, are useful as prodrugs for the treatment of diabetes. In another aspect of the invention, a general method is provided for converting compounds of formula XLV with secondary amides into substituted tertiary amides (Scheme 1). Scheme 1 Yo 185 Formula XLVR103R103 Formula XLVIRioo θRioo Formula XLVIII Formula XLIX Formula XLVII Formula L 100n---OR101 In addition to the reaction of aldehydes or ketones to give compounds of formula XLV, other processes can be used to convert secondary lactam groups. For example, alkylation followed by the addition of sodium in inert solvents, or the addition of potassium hydroxide or potassium hydroxide, can be used. 186 of sodium followed by the addition of an alkyl halide. Microwave-based synthesis procedures may also be used to convert secondary lactams into the substituted tertiary lactam compounds of this application. (For a general review, see March J. Advanced Organic Chemistry, Wiley, 1992; Inoue et al., Bull. Chem. Soc. Jpn., 58, 2721-2722, 1985; Mijin et al., J. Serb. Chem. Soc., 73(10) 945-950, 2008; Bogdal et al., Molecules, 1999, 4, 333-337; U.S. Patent No. 5,041,659). The invention also relates to the sustained administration of a compound of formula XLV by administration of a compound of formula I- III. Following administration of a compound of formula I-III, the labile Ri unit can be enzymatically or chemically cleaved, or it can be removed by first-phase metabolism to yield a compound of formula XLV. Without being bound to any specific theory, it is postulated that for some of the compounds of formula I-III, the release of a compound of formula XLV by cleavage of the Ri unit results in a therapeutically active agent. For example, such an active ingredient could be aripiprazole, ziprasidone, or bifeprunox. In one embodiment, the sustained release comprises a therapeutically effective amount of a compound of formula XLV in the patient's bloodstream for a period of at least approximately 8, preferably at least approximately 12, more preferably at least approximately 24, and even more preferably at least approximately 36 hours following administration of a compound of formula I-III.In one embodiment, the compound of formula XLV is present in the patient's bloodstream for a period selected from: at least 48 hours, at least 4 days. 187 at least one week, and at least one month. In one embodiment, a compound of formula l-lll is administered by injection. Compounds with formulas IX, X, XI, XII, XIII, XIV, XXXIII, XXXIV, XXXV, XXXVI, and XXXVII are useful for the treatment of neurological and psychological disorders. Neurological and psychiatric disorders include, but are not limited to, disorders such as brain deficits following heart bypass surgery and grafts, stroke, cerebral ischemia, spinal cord injury, head trauma, perinatal hypoxia, cardiac arrest, neuronal damage from hypoglycemia, dementia (including AIDS-induced dementia), Alzheimer's disease, Huntington's chorea, amyotrophic lateral sclerosis, eye damage, retinopathy, cognitive disorders, idiopathic and drug-induced Parkinson's disease, muscle spasms and disorders associated with muscle spasticity including tremors, epilepsy, seizures, brain deficits secondary to prolonged status epilepticus, migraine (including migraine-type headache), urinary incontinence,Substance tolerance, substance withdrawal syndrome (including substances such as opiates, nicotine, tobacco, alcohol, benzodiazepines, cocaine, sedatives, hypnotics, etc.), psychosis, schizophrenia, anxiety (including generalized anxiety disorder, panic disorder, social phobia, obsessive-compulsive disorder, and post-traumatic stress disorder (PTSD)), mood disorders (including depression, mania, bipolar disorders), circadian rhythm disorders (including jet lag and shift work disorder), trigeminal neuralgia, hearing loss, tinnitus, macular degeneration of the eye, vomiting, cerebral edema, pain (including acute pain states and, 188 chronic, severe pain, intractable pain, neuropathic pain, inflammatory pain, and post-traumatic pain), tardive dyskinesia, sleep disorders (including narcolepsy), attention deficit / hyperactivity disorder, eating disorders, and behavioral disorders. Definitions The following is a list of definitions of various terms used to describe the present invention. These definitions apply to the terms as used throughout this specification and claims, unless, in specific instances, they are otherwise limited, either individually or as part of a larger group. The term “aliphatic group” or “aliphatic” refers to a non-aromatic unit that may be saturated (e.g., with a single bond) or contain one or more unsaturated units, such as double and / or triple bonds. An aliphatic group may be linear, branched, or cyclic, may contain carbon, hydrogen, or optionally one or more heteroatoms, and may be substituted or unsubstituted. In addition to aliphatic hydrocarbon groups, aliphatic groups include, for example, polyalkoxyalkyls, such as polyalkylene glycols, polyamines, and polyimines. Such aliphatic groups may be further substituted. Aliphatic groups are understood to include alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, and substituted or unsubstituted cycloalkyl groups as described herein. The term “acyl” refers to a hydrogen-substituted carbonyl, alkyl, partially saturated or fully saturated cycloalkyl, partially saturated or fully saturated heterocycle, aryl, or 189 heteroaryl. For example, acyl includes groups such as (CrC6) alkanoyl (e.g., formyl, acetyl, propionyl, butyryl, valeryl, caproyl, t-butylacetyl, etc.), (C3-C6) cycloalkylcarbonyl (e.g., cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, etc.), heterocyclic carbonyl (e.g., pyrrolidinecarbonyl, pyrrolidine-2-one-5-carbonyl, piperidinylcarbonyl, piperazinylcarbonyl, tetrahydrofuranylcarbonyl, etc.), aroyl (e.g., benzoyl), and heteroaroyl (e.g., thiophenyl-2-carbonyl, thiophenyl-3-carbonyl, furanyl-2-carbonyl, furanyl-3-carbonyl, 1H-pyrroyl-2-carbonyl, 1H-pyrroyl-3-carbonyl, benzo[b]thiophenyl-2-carbonyl, etc.). In addition, the alkyl, cycloalkyl, heterocyclo, aryl, and heteroaryl portion of the acyl group may be any of the groups described in the respective definitions.When indicated as 'Optionally substituted', the acyl group may be unsubstituted or optionally substituted with one or more substituents (typically between one and three substituents) that are independently selected from the group of substituents in the list given later in the definition of 'substituted' or the alkyl, cycloalkyl, heterocyclo, aryl and heteroaryl portion of the acyl group may be substituted as described above in the list of preferred and most preferred substituents, respectively. The intention is that the term “alkyl” includes saturated aliphatic hydrocarbon radicals / groups, both branched and straight-chain, substituted or unsubstituted, with the specified number of carbon atoms. Preferred alkyl groups comprise from approximately 1 to approximately 24 carbon atoms (“C1-C24”), preferably from approximately 7 to approximately 24 carbon atoms (“C7-C24”), and preferably from approximately 8 to approximately 24 carbon atoms. 190 carbon (“C8-C24”), preferably between approximately 9 and approximately 24 carbon atoms (“C9-C24”). Other preferred alkyl groups comprise between approximately 1 and approximately 8 carbon atoms (“C1-C8”), such as between approximately 1 and approximately 6 carbon atoms (“C1-C3”), or between approximately 1 and approximately 3 carbon atoms (“C1-C3”). Examples of C1-C6 alkyl radicals include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, n-pentyl, neopentyl, and n-hexyl radicals. The term “alkenyl” refers to linear or branched radicals with at least one carbon-carbon double bond. Such radicals preferably contain between approximately two and approximately twenty-four carbon atoms (“C2-C24”), preferably between approximately seven and approximately twenty-four carbon atoms (“C7-C24”), preferably between approximately eight and approximately twenty-four carbon atoms (“C8-C24”), and preferably between approximately nine and approximately twenty-four carbon atoms (“C9-C24”). Other preferred alkenyl radicals are “lower alkenyl” radicals with between two and approximately ten carbon atoms (“C2-C10”), such as ethenyl, allyl, propenyl, butenyl, and 4-methylbutenyl. Preferred lower alkenyl radicals include between 2 and approximately 6 carbon atoms (“C2-C6”). The terms “alkenyl” and “lower alkenyl” encompass radicals with “cis” and “trans” orientations, or alternatively, “Έ” and “Z” orientations. The term “alkynyl” refers to linear or branched radicals with at least one carbon-carbon triple bond. Such radicals preferably contain between approximately two and approximately twenty-four atoms. 191 of carbon (“C2-C24”) preferably between approximately 7 and approximately 24 carbon atoms (“C7-C24”), preferably between approximately 8 and approximately 24 carbon atoms (“C8-C24”), and preferably between approximately 9 and approximately 24 carbon atoms (“C9-C24”). Other preferred alkynyl radicals are “lower alkynyl” radicals with between two and approximately ten carbon atoms such as propargyl, 1-propynyl, 2-propynyl, 1-butyne, 2-butynyl, and 1-pentynyl. Preferred lower alkynyl radicals include between two and approximately six carbon atoms (“C2-C6”). The term “cycloalkyl” refers to saturated carbocyclic radicals with between three and approximately twelve carbon atoms (“C3-C12”). Examples of such radicals include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. The term “cycloalkenyl” refers to partially unsaturated carbocyclic radicals with between three and twelve carbon atoms. Cycloalkenyl radicals that are partially unsaturated carbocyclic radicals containing two double bonds (which may or may not be conjugated) can be called “cycloalkyldienyl.” The most preferred cycloalkenyl radicals are “lower cycloalkenyl” radicals with between four and approximately eight carbon atoms. Examples of such radicals include cyclobutenyl, cyclopentenyl, and cyclohexenyl. The term “alkylene,” as used herein, refers to the divalent group derived from a linear or branched saturated hydrocarbon chain with the specified number of carbon atoms. 192 Examples of alkylene groups include, but are not limited to, ethylene, propylene, butylene, 3-methylpentylene, and 5-ethylhexylene. The term “alkenylene,” as used herein, denotes a divalent group derived from a linear or branched hydrocarbon chain unit containing the specified number of carbon atoms and having at least one carbon-carbon double bond. Alkenylene groups include, but are not limited to, ethenylene, 2-propenylene, 2-butenylene, 1-methyl-2-buten-1-ylene, and so on. The term “alkynylene,” as used herein, denotes a divalent group derived from a linear or branched hydrocarbon chain unit containing the specified number of carbon atoms and having at least one carbon-carbon triple bond. Representative alkynylene groups include, but are not limited to, propynylene, 1-butynylene, 2-methyl-3-hexynylene, and so forth. The term “alkoxy” refers to linear or branched radicals containing oxy-, each of which has alkyl portions of between one and approximately twenty-four carbon atoms, or preferably between one and approximately twelve carbon atoms. The most preferred alkoxy radicals are the “lower alkoxy” radicals with between one and approximately ten carbon atoms, and more preferably with between one and approximately eight carbon atoms. Examples of such radicals include methoxy, ethoxy, propoxy, butoxy, and tert-butoxy. The term “alkoxyalkyl” refers to alkyl radicals with one or more alkoxy radicals attached to the alkyl radical, i.e., to form monoalkoxyalkyl and dialkoxyalkyl radicals. 193 The term “aryl”, alone or in combination, refers to an aromatic carbocyclic system containing one, two, or three rings, where these rings may be linked together as pendant groups or fused together. The term “aryl” encompasses aromatic radicals such as phenyl, naphthyl, tetrahydronaphthyl, indane, and biphenyl. The terms “heterocyclyl,” “heterocycle,” “heterocyclic,” or “heterocycle” refer to ring-shaped radicals containing heteroatoms, which are saturated, partially unsaturated, and unsaturated. These can also be called “heterocyclyl,” “heterocycloalkenyl,” and “heteroaryl,” respectively, where the heteroatoms can be selected from nitrogen, sulfur, and oxygen. Examples of saturated heterocyclyl radicals include saturated heteromonocyclic groups of 3 to 6 members containing 1 to 4 nitrogen atoms (e.g., pyrrolidinyl, imidazolidinyl, piperidine, piperazinyl, etc.); and saturated heteromonocyclic groups of 3 to 6 members containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms (e.g., morpholinyl, etc.). Saturated heteromonocyclic groups of between 3 and 6 members containing between 1 and 2 sulfur atoms and between 1 and 3 nitrogen atoms (e.g., thiazolidinyl, etc.).Examples of partially unsaturated heterocyclyl radicals include dihydrothiophene, dihydropyran, dihydrofuran, and dihydrothiazole. Heterocyclyl radicals may contain a pentavalent nitrogen, as in tetrazolium and pyridinium radicals. The term "heterocycle" also encompasses radicals where heterocyclyl radicals are fused to aryl or cycloalkyl radicals. Examples of such fused bicyclic radicals include benzofuran, benzothiophene, and so on. 194 The term “heteroaryl” refers to unsaturated aromatic heterocyclic radicals. Examples of heteroaryl radicals include unsaturated heteromonocyclic groups of 3 to 6 members containing 1 to 4 nitrogen atoms, e.g., pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, pyrimidiyl, pyrazinyl, pyridazinyl, triazolyl (e.g., 4H-1,2,4-triazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, etc.), tetrazolyl (e.g., 1H-tetrazolyl, 2H-tetrazolyl, etc.), etc.; Condensed unsaturated heterocyclic groups containing between 1 and 5 nitrogen atoms, for example, indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl, indazolyl, benzotriazolyl, tetrazolopyridazinyl (for example, tetrazolo[1,5-b]pyridazinyl, etc.), etc.; unsaturated heteromonocyclic groups of between 3 and 6 members containing one oxygen atom, for example, pyranyl, furyl, etc.; unsaturated heteromonocyclic groups of between 3 and 6 members containing one sulfur atom, for example, thienyl, etc.; unsaturated heteromonocyclic groups of between 3 and 6 members containing between 1 and 2 oxygen atoms and between 1 and 3 nitrogen atoms, for example, oxazolyl, isoxazolyl, oxadiazolyl (for example, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, etc.) etc.; fused unsaturated heterocyclyl groups containing between 1 and 2 oxygen atoms and between 1 and 3 nitrogen atoms (for example, benzoxazolyl, benzoxadiazolyl, etc.); unsaturated heteromonocyclic groups of between 3 and 6 members containing between 1 and 2 sulfur atoms and between 1 and 3 nitrogen atoms, for example, thiazolyl, thiadiazolyl (for example, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, etc.) etc.; fused unsaturated heterocyclyl groups containing between 1 and 2 sulfur atoms and between 1 and 3 nitrogen atoms (for example, benzothiazolyl,. 195 benzothiadiazolyl, etc.) etcetera. The term “heterocycloalkyl” refers to alkyl radicals substituted with heterocycles. The most preferred heterocycloalkyl radicals are the “lower heterocycloalkyl” radicals with between one and six carbon atoms in the heterocycle radical. The term “alkylthio” refers to radicals containing a linear or branched alkyl group of one to approximately ten carbon atoms bonded to a divalent sulfur atom. Preferred alkylthio radicals have alkyl groups of one to approximately twenty-four carbon atoms, or preferably one to approximately twelve carbon atoms. The most preferred alkylthio radicals are “lower alkylthio” radicals with one to approximately ten carbon atoms. Most preferred are alkylthio radicals with lower alkyl groups of one to approximately eight carbon atoms. Examples of such lower alkylthio radicals include methylthio, ethylthio, propylthio, butylthio, and hexylthio. The terms “aralkyl” or “arylalkyl” refer to alkyl radicals substituted with aryl such as benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, and diphenylethyl. The term “aryloxy” refers to aryl radicals bonded to other radicals through an oxygen atom. The terms “aralkoxy” or “arylkoxy” refer to aralkyl radicals linked through an oxygen atom to other radicals. The term “aminoalkyl” refers to alkyl radicals substituted with amino radicals. Preferred aminoalkyl radicals have alkyl radicals 196 with between approximately one and approximately twenty-four carbon atoms or, preferably, between one and approximately twelve carbon atoms. The most preferred aminoalkyl radicals are "lower aminoalkyl" radicals, which have alkyl groups with between one and approximately ten carbon atoms. The most preferred are aminoalkyl radicals with lower alkyl groups with between one and eight carbon atoms. Examples of such radicals include aminomethyl, aminoethyl, and so on. The term “alkylamino” denotes an amino group substituted with one or two alkyl radicals. Preferred alkylamino radicals have alkyl groups with between approximately one and approximately twenty carbon atoms, or preferably between one and approximately twelve carbon atoms. Even more preferred alkylamino radicals are “lower alkylamino” radicals, which have alkyl groups with between one and approximately ten carbon atoms. The most preferred radicals are alkylamino radicals with lower alkyl groups having between one and approximately eight carbon atoms. Suitable lower alkylamino radicals may be monosubstituted N-alkylamino or disubstituted N,N-alkylamino, such as N-methylamino, N-ethylamino, N,N-dimethylamino, N,N-diethylamino, or others like them. The term “substituted” refers to the replacement of one or more hydrogen radicals in a given structure by the substituent radical specified, which include, but are not limited to: halo, alkyl, alkenyl, alkynyl, aryl, heterocyclyl, thiol, alkylthio, arylthio, alkylthioalkyl, arylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl, arylsulfonylalkyl, alkoxy, aryloxy, aralkoxy, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkoxycarbonyl, 197 aryloxycarbonyl, haloalkyl, amino, trifluoromethyl, cyano, nitro, alkylamino, arylamino, alkylaminoalkyl, arylaminoalkyl, aminoalkylamino, hydroxy, alkoxyalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, acyl, aralkoxycarbonyl, carboxylic acid, sulfonic acid, sulfonyl, phosphonic acid, aryl, heteroaryl, heterocyclic, and aliphatic. It is understood that the substituent may be further substituted. For simplicity, the chemical units defined and referenced throughout this document may be univalent chemical units (e.g., alkyl, aryl, etc.) or multivalent units under appropriate structural circumstances that are clear to those skilled in the art. For example, an “alkyl” unit may refer to a monovalent radical (e.g., CH3-CH2-), or in other instances, a bivalent connecting unit may be an “alkyl,” in which case those skilled in the art will understand that the alkyl will be a divalent radical (e.g., -CH2-CH2-), which is equivalent to the term “alkylene.”Similarly, in circumstances where divalent units are necessary and it is specified that they are “alkoxy”, “alkylamino”, “aryloxy”, “alkylthio”, “aryl”, “heteroaryl”, “heterocyclic”, “alkyl”, “alkenyl”, “alkynyl”, “aliphatic”, or “cycloalkyl”, those experienced in the art will understand that the terms “alkoxy”, “alkylamino”, “aryloxy”, “alkylthio”, “aryl”, “heteroaryl”, “heterocyclic”, “alkyl”, “alkenyl”, “alkynyl”, “aliphatic”, or “cycloalkyl” refer to the corresponding divalent unit. The terms “halogen” or “halo” as used herein, refer to an atom selected from fluorine, chlorine, bromine, and iodine. The terms “compound”, “drug”, and “prodrug” as used herein 198 This includes all pharmaceutically acceptable salts, co-crystals, solvates, hydrates, polymorphs, enantiomers, diastereomers, racemates, etc., of compounds, drugs, and prodrugs with the formulas set forth herein. Substituents that are indicated as attached through variable attachment points may be attached to any available position on the ring structure. As used herein, the expression “effective amount of the subject compound”, with respect to the subject treatment method, refers to an amount of the subject compound that, when administered as part of a desired dosage regimen, enables management of the disease or disorder to clinically acceptable standards. “Treatment” or “treat” refers to an approach to achieving a beneficial or desired clinical outcome in a patient. For the purposes of the present invention, beneficial or desired clinical outcomes include, but are not limited to, one or more of the following: relief of symptoms, reduction of the extent of a disease, stabilization of a disease state (i.e., that it does not worsen), prevention of the spread (i.e., metastasis) of a disease, prevention of the occurrence or recurrence of the disease, retardation or slowing of disease progression, improvement of the disease state, and remission (whether partial or complete). The term “labile” as used herein refers to the ability of the prodrug of the invention to undergo enzymatic and / or chemical cleavage in vivo to form the parent drug. As used herein, the term “prodrug” means a compound as disclosed herein, which is a labile compound derived from a heteroaromatic parent drug containing 199 NH- which, when administered in vivo to a patient, is olvided by chemical and / or enzymatic hydrolysis to form the original drug in such a way that a sufficient quantity of the compound to be administered to the patient is available for the intended therapeutic use in the form of sustained release. Pharmaceutical compositions The pharmaceutical compositions of the present invention comprise a therapeutically effective amount of a compound of the present invention formulated together with one or more pharmaceutically acceptable vehicles or excipients. As used herein, the term “pharmaceutically acceptable vehicle or excipient” means a non-toxic, solid, semi-solid, gel or inert liquid material, used as a filler, diluent, encapsulant or auxiliary formulation of any kind.Some examples of materials that can serve as pharmaceutically acceptable vehicles are sugars such as lactose, glucose, and sucrose; cyclodextrins such as alpha-(α), beta-(β), and gamma-(γ) cyclodextrins; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose, and cellulose acetate; tragacanth gum powder; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; glycols such as propylene glycol; esters such as ethyl oleate and ethyl laurate; agar-agar; pH buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; and isotonic saline solution. 200 Ringer's solution; ethyl alcohol, and phosphate pH buffer solutions, as well as other compatible non-toxic lubricants such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, mold release agents, coating agents, the composition may also contain sweeteners, flavorings and perfumes, preservatives and antioxidants, according to the judgment of the formulator. The pharmaceutical compositions of the present invention can be administered orally, parenterally, by spray inhalation, topically, rectally, nasally, buccally, vaginally, or via an implanted reservoir. In a preferred embodiment, administration is parenteral by injection. The pharmaceutical compositions of the present invention may contain any conventional, pharmaceutically acceptable, non-toxic adjuvant or vehicle. In some cases, the pH of the formulation may be adjusted with pharmaceutically acceptable acids, bases, or pH buffer solutions to increase the stability of the formulated compound or its route of administration. As used herein, the term parenteral includes subcutaneous, intracutaneous, intravenous, intramuscular, intra-articular, intra-arterial, intrasynovial, intrastem, intrathecal, intralesional, and intracranial injection or infusion techniques. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and elixirs. In addition to the active compounds, liquid dosage forms may contain inert diluents commonly used in the art, such as water or other solvents. 201. Solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, peanut, corn, wheat germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters, and sorbitan, and mixtures thereof. In addition to inert diluents, oral compositions may also include adjuvants such as wetting agents, emulsifying and suspending agents, sweeteners, flavorings, and perfumes. Injectable preparations, such as sterile aqueous or oil-based injectable suspensions, may be formulated according to known best practices using appropriate dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable suspension or emulsion, such as INTRALIPID®, LIPOSYN®, or OMEGAVEN®, or a solution in a non-toxic diluent or solvent acceptable for parenteral administration, such as a solution in 1,3-butanediol. INTRALIPID® is an intravenous fat emulsion containing 10-30% soybean oil, 1-10% egg yolk phospholipids, 1-10% glycerin, and water. LIPOSYN® is also an intravenous fat emulsion containing 2-15% safflower oil, 2-15% soybean oil, 0.5-5% egg phosphatides, 1-10% glycerin, and water. OMEGAVEN® is an infusion emulsion containing approximately 5-25% fish oil, 0.5-10% egg phosphatides, 1-10% glycerin, and water.Acceptable vehicles and solvents that can be used include: water, Ringer's solution, USP solution, and isotonic sodium chloride solution. Additionally, as solvents. 202 Sterile, fixed oils are conventionally used as suspension media. Any soft, fixed oil, including synthetic mono- or diglycerides, can be used for this purpose. In addition, fatty acids such as oleic acid are used in the preparation of injectables. Injectable formulations can be sterilized, for example, by filtration through a bacterial retention filter, or by incorporating sterilizing agents in the form of sterile solid compositions that can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use. The additional sustained release according to the invention can be achieved by using a liquid suspension of crystalline or amorphous material with poor water solubility. The absorption rate of the drug therefore depends on its dissolution rate, which, in turn, may depend on the crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered drug form is achieved by dissolving or suspending the drug in an oily vehicle. Injectable depot forms are made by forming microencapsulated matrices of the drug in biodegradable polymers such as polylactide-polyglycolide. Depending on the drug-to-polymer ratio and the nature of the particular polymer used, the drug release rate can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides).Depot injectable formulations are also prepared by trapping the drug in liposomes or microemulsions that are compatible with body tissues. In a preferred embodiment, the formulation provides a system 203 A sustained-release delivery system is used to minimize the prodrug's exposure to water. This can be achieved by formulating the prodrug with a sustained-release delivery system that is a polymer matrix capable of minimizing water diffusion within the matrix. Suitable polymers that may comprise the matrix include polylactide (PLA) polymers and lactide / glycolide (PLGA) copolymers. Alternatively, the sustained-release delivery system may comprise polyanionic molecules or resins suitable for injection or oral administration. Suitable polyanionic molecules include cyclodextrins and polysulfonates formulated to form a poorly soluble mass that minimizes the prodrug's exposure to water and allows the prodrug to be released slowly. Compositions for rectal or vaginal administration are preferably suppositories that can be prepared by mixing the compounds of the present invention with suitable non-irritating excipients or vehicles such as cocoa butter, polyethylene glycol, or a suppository wax, which are solid at room temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound. Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is mixed with at least one pharmaceutically acceptable inert excipient or vehicle, such as sodium citrate or dicalcium phosphate, and / or: a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid, b) binders such as, 204 For example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose, and acacia gum; c) humectants such as glycerol; d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate; e) dissolution retarders such as paraffin; f) absorption accelerators such as quaternary ammonium compounds; g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate; h) absorbents such as kaolin and bentonite clay; and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets, and pills, the dosage form may also include pH buffering agents. Solid compositions of a similar type can also be used as fillers in soft or hard filled gelatin capsules using excipients such as lactose or milk sugar as well as high molecular weight polyethylene glycols etc. Solid dosage forms such as tablets, coated tablets, capsules, pills, and granules can be prepared with coatings and facings such as enteric coatings and other coatings well-known in the art of pharmaceutical formulation. These may optionally contain opacifying agents and can also be made in a composition such that they release the active ingredient(s) alone, or preferably, in a certain part of the intestinal tract, optionally in a delayed manner. Examples of coating compositions that may be used include polymeric substances and waxes. 205 Dosage forms for topical or transdermal administration of a compound of the present invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants, or patches. The active component is mixed under sterile conditions with a pharmaceutically acceptable vehicle and all necessary preservatives or pH buffers. Ophthalmic formulations, ear drops, ophthalmic ointments, and powders and solutions are also contemplated to be within the scope of the present invention. Ointments, pastes, creams and gels may contain, in addition to an active compound of the present invention, excipients such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth gum, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof. The powders and sprays may contain, in addition to the compounds of the present invention, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates, and polyamide powder, or mixtures of such substances. The sprays may also contain customary propellants such as chlorofluorohydrocarbons. Transdermal patches have the added advantage of providing controlled delivery of a compound to the body. Such dosage forms can be made by dissolving or dosing the compound in the appropriate medium. Absorption enhancers can also be used to increase the flow of the compound through the skin. The rate can be controlled either by providing a membrane to control the rate or 206 dispersing the compound in a polymer matrix or gel. For pulmonary administration, a therapeutic composition of the invention is formulated and administered to the patient in the form of a solid or liquid particulate by direct administration, for example, by inhalation into the respiratory system. The solid or liquid particulate forms of the active compound prepared to implement the present invention include respirable-sized particles: that is, particles of a size small enough to pass through the mouth and larynx upon inhalation and into the bronchi and pulmonary alveoli. The administration of aerosolized therapeutic principles, particularly aerosolized antibiotics, is known in the art (see, for example, U.S. Patent No. 5,767,068 to VanDevanter et al., U.S. Patent No. 5,508,269 to Smith et al., and WO 98 / 43650 to Montgomery, all of which are incorporated herein by reference).An exposition on the pulmonary administration of antibiotics can also be seen in U.S. Patent No. 6,014,969, which is incorporated herein by reference. A “therapeutically effective amount” of a prodrug compound of the invention means an amount of the compound that confers a therapeutic effect on the treated subject, with a reasonable benefit / risk ratio applicable to any medical treatment. The therapeutic effect may be objective (i.e., measurable by some test or marker) or subjective (i.e., perceived or felt by the subject). According to the invention, the therapeutically effective amount of a prodrug of the invention is typically based on the amount of the drug of 207 Source for the therapeutic target. Dosage and dosage frequency information can be readily obtained for many of the source drugs from which the prodrugs of the invention are derived, and the amount for the therapeutic target can be calculated for each prodrug of the invention. According to the invention, the same dose of a prodrug of the invention provides a longer duration of therapeutic effect compared to the source drug. Therefore, if a single dose of the source drug provides 12 hours of therapeutic effectiveness, a prodrug of that same source drug according to the invention that provides therapeutic effectiveness for more than 12 hours will be considered to achieve a “sustained release.” The precise dosage of a prodrug of the invention depends on several factors, including the nature and dosage of the parent drug and the chemical characteristics of the prodrug unit attached to the parent drug. Ultimately, the effective dosage and dosage frequency of a prodrug of the invention will be determined by the attending physician, within the scope of sound medical judgment.The specific therapeutically effective dose level and dosing frequency for any particular patient will depend on a variety of factors, including the disorder being treated and the severity of the disorder; the activity of the specific compound being used; the specific composition being used; the patient's age, body weight, general health status, sex, and diet; the timing, route of administration, and excretion rate of the specific compound being used; the duration of treatment; drugs being used in combination with or concurrently with the specific compound being used; and other factors. 208 similar ones well known in medical science. EXAMPLES The compounds and processes of the present invention will be better understood in connection with the following Examples, which are given only for illustration and not to limit the scope of the invention. There will be various changes and modifications to the disclosed embodiments that will be obvious to those skilled in the art, and such changes and modifications, including, without limitation, those relating to the chemical structures, substituents, derivatives, formulations, and / or methods of the invention, may be made without departing from the spirit of the invention or the scope of the appended claims. The general methodology for the preparation of lactam compounds can be found in the following publications: U.S. Patent No. 7,160,888; U.S. Patent No. 5,462,934; U.S. Patent No. 4,914,094; U.S. Patent No. 4,234,584; U.S. Patent No. 4,514,401; U.S. Patent No. 5,462,934; U.S. Patent No. 4,468.402; WO 2006 / 090273 A2; WO 2008 / 150848 A1; WO. 2006 / 112464 A1; WO 2008 / 132600 A1. BnNCO, DMAP, NEt3 Cl ci OH O Example 2 EITHER EITHER Preparation of 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-1)butoxy)-1209 (hydroxymethyl)-3,4*dihydroquinolin-2(1H)-one (Example 1: compound A1) A mixture of aripiprazole (20 g, 45 mmol), triethylamine (1 ml, 7.1 mmol), formaldehyde (37% aqueous solution, 70 ml), and dimethylformamide (200 ml) was heated to 80°C for 20 h. The reaction mixture was cooled, diluted with ethyl acetate (400 ml), and washed with water / brine (1:1, 3 x 500 ml). The organic phase was dried over MgSO4, filtered, and evaporated to dryness under vacuum to give the hemi-aminal A1 as a white solid (18.6 g, containing 25% aripiprazole, 65% yield based on A1). 1H NMR (CDCh, 300MHz) complex mixture of signals due to contamination with Aripiprazole, main signal δ 5.34 (s, 2H, OHCHpN): m / z (M+H) 478 and 480. benzylcarbamate of (7-(4-(4-(2,3-dichlorophenyl)piperazin-1 -yl)butoxy)-2-oxo- 3,4-dihydroquinoline-1(2H)-yl)methyl (Example 2: compound 28) To a solution of hemi-aminal A1 from Example 1 (4 g, 8.4 mmol), 4-dimethylaminopyridine (0.15 g, 1.3 mmol), and triethylamine (1.1 mL, 7.5 mmol) in dichloromethane (30 mL), benzylisocyanate (1.03 mL, 8.3 mmol) was added, and the reaction mixture was stirred for 24 hours. The reaction mixture was then heated at 35°C for 20 hours, cooled, and washed with water / brine (1:1, 50 mL). The organic phase was dried over MgSO4, filtered, and evaporated under vacuum. The residue was further purified by chromatography on silica by eluting with ethyl acetate / dichloromethane / methanol (1:1:0.1) to give the desired product as a whitish foam (530 mg, 14% yield).1H NMR (CDCI3, 300MHz) δ 1.58-1.88 (m, 4H), 2.48 (t, 2H), 2.60-2.72 (m, 6H), 2.85 (m, 2H), 300-3.12 (m, 4H), 3.96 (t, 2H), 4.40 (d, 2H), 5.13 (NH), 5.96 (s, 2H), 6.58 (dd, 1H), 6.79 (d, 1H), 6.92-6.98 (m, 1H), 7.04 (d, 1H), 7.12-7.16 (m, 1H), 7.23-7.35 (m, 6H); m / z (M+H) 611.12 and 613.10. 210 The following compounds were prepared in a manner analogous to Example 2. (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methylethyl carbonate (Example 3: compound 79) The desired product was isolated as a yellow oil (830 mg, 24% yield).1H NMR (δ6-DMSO, 300MHz) δ 1.78 (t, 3H), 1.52-1.61 (m, 2H), 1.63-1.76 (m, 2H), 2.31-2.40 (m, 2H), 2.40-2.60 (m, 6H), 2.73-2.80 (m, 2H), 2.91-2.99 (m, 4H), 3.96 (t, 3H), 4.11 (q, 2H), 5.87(s, 2H), 6.60-6.70 (m, 2H), 7.07-7.12 (m, 2H), 7.24-7.30 (m, 2H); m / z (M+H) 550.48 and 552.40. butyl carbonate-(7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo- 3,4-dihydroquinolin-1(2H)-yl)methyl (Example 4: Compound 80) The desired product was isolated as a yellow oil (750mg, 21% yield).1H NMR (CDCh, 300MHz) δ 0.92 (t, 3H), 1.33-1.45 (m, 2H), 1.59-1.80 (m, 4H), 1.80–1.92 (m, 2H), 2.49 (t, 2H), 2.58–2.75 (m, 6H), 2.85 (t, 2H), 3.00–3.13 (m, 4H), 3.98 (t, 29), 4.H18 (t, 2H), 4.H18 (t, 2, (d, 1H), 6.67 (d, 1H), 6.92- 6.99 (m, 1H), 7.03 (dd, 1H), 7.10–7.20 (m, 2H); m / z (M+H) of 578.10 and 580.08. carbonate of (7-(4-(4-(2,3-dichlorophenyl)piperazine-1-yl)butoxy)-2-oxo-3,4dihydroquinoljn-1(2H)-yl)methylhexyl (Example 5: compound 81) The desired product was isolated as yield from (1,2%N (de-DMSO, 300MHz) δ 0.80 (t, 3H), 1.15–1.30 (m, 6H), 1.50–1.60 (m, 4H), 1.65–1.73 (m, 2H), 2.35 (t, 2H, 2.6H), 2.6H–41 2H), 2.88–3.00 (m, 4H), 3.95 (t, 2H), 4.06 (t, 2H), 5.86 (s, 2H), 6.60–6.70 (m, 2H), 7.05–7.15 (m, 2H), 7.22); m / z (M+H) of 606.15 and 608.15. decyl carbonate (7-(4-(4-(2,3-dichlorophenyl)piperazine-1 -yl)butoxy)-2-oxo- 3,4-dihydroquinoline-1(2H)-yl)methyl (Example 6: compound 82) The desired product was isolated as a yellow oil (1.42g, 46% yield).1H 211 y RMN (de-DMSO, 300MHz) δ 0.79 (m, 3H), 1.13-1.30 (m, 14H), 1.48-1.60 (m, 4H), 1.65-1.75 (m, 2H), 2.33 (t, 2H), 2.41-2.60 (m, 6H), 2.72-2.80 (m, 2H), 2,892.98 (m, 4H), 3.95 (t, 2H), 4.05 (t, 2H), 5.86 (s, 2H), 6.60-6.70 (m, 2H), 7.05- 7,13 (m, 2H), 7,22-7,28 (m, 2H); m / z (M+H) 662.56 y 664.54. carbonate of (7-(4-(4-(2,3-diclorofenil)piperazin-1-il)butoxi)-2-oxo-3,4f dihydroquinolin-1(2H)-il)metilhexadecilo (Ejemplo 7: compuesto 83) The product is made from amarillo aceite (1.55 g, 44% of rendimiento).1H ​​RMN (d6-DMSO, 300MHz) δ 0.80 (t, 3H), 1.10-1.29 (m, 26H), 1.49-1.60 (m, 4H), 1.65-1.75 (m, 2H), 2.33 (t, 2H), 2.43-2.55 (m, 6H), 2.78 (t, 2H), 2.90-2.95 (m, 4H), 3.95 (t, 2H), 4.05 (t, 2H), 5.84 (s, 2H), 6.60-6.68 (m, 2H), 7.05-7.12 (m, 2H), 7.24-7.29 (m, 2H); m / z (M-Ci0H20)+606.52 y 608.54. (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinolin1(2H)-yl)methylmorpholine-4-carboxylate (Example 8: compound 49) The desired product was isolated as a yellow oil (15.52% g yield).1H NMR (de-DMSO, 300MHz) δ 1.50-1.75 (m, 4H), 2.35 (t, 2H), 2.42-2.61 (m, 6H), 2.70-2.82 (m, 2H), 2.88-3.00 (m, 4H), 3.26-3.40 (m, 4H), 3.40-3.60 (m, 4H), 3.94 (t, 2H, 21H), (s, 2.6H), (s, 61H). 1H), 6.68 (d, 1H), 7.05- 7.13 (m, 2H), 7.20-7.30 (m, 2H); m / z(M+H) 591.11 and 593.15. diethylcarbamate of (7-(4-(4-(2,3-dichlorophenyl)piperazin-1 -yl)butoxy)-2-oxo- 3,4-dihydroquinoline-1(2H)-yl)methyl (Example 9: compound 84) The desired product was isolated as a yellow oil (0.83g, 31% yield).1H NMR (CDCh, 300MHz) δ (m, 4H), 2.45-2.52 (m, 2H), 2.58-2.83 (m, 6H), 2.82-2.90 (m, 2H), 3.00-3.12 (m, 4H), 3.18-3.38 (m, 4H), 3.18-3.38 (m, 4H), t 6.58 (dd, 1H), 6.77 (d, 1H), 6.94-6.98 (m, 1H), 7.06 (d, 1H), 7.15-7.20 (m, 2H); m / z (M+H) 577.48 and 579.46. 212 carbonate of (7-(4-(4-(2,3-dichlorophenyl)piperazin-1 -yl)butoxy)-2-oxo-3,4dihydroquinolin-1(2H)-yl)methylsopent¡lo (Example 10: compound 85) A solution of phosgene (20% in toluene, 54 mL, 110 mmol) in tetrahydrofuran (100 mL) was added to a solution of 3-methyl-1-butanol (1.7 mL, 15.7 mmol) in tetrahydrofuran (50 mL) for 1 hour. After 4 hours, the volatile materials were removed under vacuum, and the residue was added to a solution of hemi-aminal A1 (3 g, 4.7 mmol), 4-dimethylaminopyridine (0.3 g, 1.9 mmol), pyridine (10 mL), and triethylamine (1.3 mL, 9.4 mmol) in dichloromethane (30 mL). After stirring for 72 hours, the reaction mixture was diluted with ethyl acetate (100 mL) and washed with 5% aqueous NaHCO3 / brine (1:1,100 mL). The organic phase was dried over MgSO4, filtered, and evaporated under vacuum. The residue was further purified by silica chromatography by eluting with ethyl acetate / dichloromethane / methanol (1:1:0.1) to give the desired product as a yellow oil (1.54 g, 55% yield).1H NMR (CDCI3, 300MHz) δ 1.90-1.95 (m, 6H), 1.50-1.60 (m, 4H), 1.65-1.79 (m, 2H), 1.79-1.89 (m, 2H), 2.50 (t, 2H), 2.60-2.72 (m, 6H), 2.82-2.90 (m, 2H), 3.023.11 (m, 4H), 3.98 (t, 2H), 4.21 (t, 2H), 5.92 (s, 2H), 6.56 (dd, 1H), 6.67 (d, 1H), 6.95-7.00 (m, 1H), 7.05 (d, 1H), 7.13-7.19 (m, 2H); m / z (M+H) 592.48 y 594.46. de (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4dihidroquinolin-1(2H)-yl)methyl acetate (Example 11: compuesto 1). acetic anhydride THF, 60 °C A solution of the Compound-Ai of Example-1, (50.63 g, 0.105 mol) in anhydrous tetrahydrofuran (THF, 80 ml) was treated with acetic anhydride (15.3 ml, 213 0.16 mol) and was heated for 2.0 hours at 60°C (oil bath). To this solution, triethylamine (2.0 mL, 0.014 mol) was added and stirred for 16 hours at 60°C. The solvent was removed using a rotary evaporator. To the resulting crude mixture, ethyl acetate (150 mL) and heptane (50 mL) were added. The solution was washed with NaHCO3 (5% aqueous solution, 250 mL). After the separation of the two phases, the pH of the aqueous layer was adjusted above 7. The aqueous layer was further extracted using the organic mixture. The organic layer was separated and washed with 5% NaHCO3 solution, followed by deionized water and brine. The solution was dried using anhydrous MgSC4, filtered, and evaporated under vacuum. The resulting product was purified using column chromatography on silica gel with ethanol:ethyl acetate (5:95) as the eluent. The fractions containing the desired product were combined and d-tartaric acid (12.5 g dissolved in 60:5 ethanol: water) was added to cause precipitation of the desired product (48.78 g, 89% yield).1H NMR (CDCI3, 300MHz) δ 1.73 (m, 2H), 1.84 (m, 2H), 2.12 (s, 3H), 2.50 (t, 2H), 2.68 (m, 6H), 2.87 (dd, 2H), 3.08 (m, 4H), 3.98 (t, 2H), 5.91 (s, 2H), 6.59 (m, 2H), 6.96 (dd, 1H), 7.08 (dd, 1H), 7.15 (m, 2H). The following compounds were prepared in a manner analogous to Example 11. (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl dodecanoate (Example 12: Compound 7) The desired product was isolated as a crystalline solid (0.3 g, 21% yield). The molecular weight was confirmed by mass spectrometry analysis. Figures 2-6 show the PXRD, IR, Raman, and TGA spectra of the desired product. 1H NMR (CDCI3, 300 MHz) δ 0.87 (t, 3H), 1.24 (m, 16H), 1.62 (m, 2H), 214 1.83 (m, 2H), 1.86 (m, 2H), 2.36 (t, 2H), 2.49 (t, 2H), 2.68 (m, 6H), 2.86 (dd, 2H), 3.08 (m, 4H), 3.97 (t, 2H), 5.91 (s, 2H), 6.59 (m, 2H), 6.96 (dd, 1H), 7.07 (dd, 1H), 7.14 (m, 2H). See Figures 1-5 for additional characterization (PXRD, IR, Raman, TGA and DSC spectra) of Compound 7. (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4dihydroquinolin-1(2H)-yl)methyl palmitate (Example 13: Compound 10) The desired product was isolated as a crystalline solid (4.2 g, 70% yield). The molecular weight (716.6) was confirmed by mass spectrometry analysis. 1H NMR (CDCI3, 300MHz) δ 0.88 (t, 3H), 1.25 (m, 24H), 1.64 (m, 2H), 1.72 (m, 2H), 1.84 (m, 2H), 2.36 (t, 2H), 2.49 (t, 2H), 2.68 (m, 6H), 2.86 (dd, 2H), 3.08 (m, 4H), 3.97 (t, 2H), 5.92 (br s, 2H), 6.59 (dd, 1H), 6.60 (s, 1H), 6.96 (dd, 1H), 7.07 (d, 1H), 7.14 (m,2H). (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4dihydroquinolin-1(2H)-yl)methyl decanoate (Example 14: Compound 6) The chloromethyl ester above was dried on 4A molecular sieves. A solution of aripiprazole (45 g, 0.1 mol) in 1,4-dioxane (800 mL) was sonicated to completely dissolve the aripiprazole, and then treated with NaH (38 g, 0.95 mol, 60% dispersion) in a portion. After shaking this mixture of The reaction was carried out at 215°C for 15 minutes at room temperature. The reaction mixture was then dropwise treated with chloromethyl ester (0.3 mol.) and a catalytic amount of sodium iodide (0.05 mol.). The resulting cloudy mixture was heated to 90°C for 2 hours, cooled to room temperature, and poured over water. The product was extracted with ethyl acetate, and the combined ethyl acetate phases were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Column chromatography on silica gel gave the desired product (12.5 grams, 70% yield). 2H), 2.50 (t, 2H), 2.68 (m, 6H), 2.86 (t, 2H), 3.08 (m, 4H), 3.97 (t, 2H), 5.92 (s, 2H), 6.58 (dd, 1H), 6.61 (d, 1H), 6.94 (dd, 1H), 7.06 (d, 1H), 7.14- 7.17 (m, 2H); m / z (M+H) 632.88. The following compounds (Examples 15-29) were prepared in a manner analogous to Example 2: (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl benzoate (Example 15, Compound 31) The desired product was isolated as a yellow oil. 1H NMR (CDCh, 300MHz) δ 1.60-1.85 (m, 4H), 2.45 (t, 2H), 2.55-2.70 (m, 4H), 2.70-2.78 (m, 2H), 2.85-2.92 (m, 2H), 3.00-3.10 (m, 4H), 3.94 (t, 2H), 6.16 (s, 2H), 6.60 (d, 1H), 6.72 (dd, 1H), 6.90-6.95 (m, 1H), 7.05-7.18 (m, 2H), 7.35-7.42 (m, 2H), 7.52-7.60 (m, 1H), 8.00-8.08 (m, 2H). m / z(M+H) 582.3. (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl butyrate (Example 16, Compound 2) The desired product was isolated by chromatography on silica eluting with ethyl acetate / dichloromethane / methanol (1:1:0.1) to give a yellow oil (2.0g, 87% of 216 c yield).1Η RMN (CDCI3, 300ΜΗζ) δ 0.94 (t, 3Η), 1.60-1.90 (m, 6Η), 2.34 (t, 2H), 2.51 (t, 2H), 2.61-2.73 (m, 6H), 2.82-2.90 (m, 2H), 3.02-3.12 (m, 4H), 3.96 (t, 2H), 5.91 (s, 1H), 6.55-6.61 (m, 2H), 6.93-6.98 (m, 1H), 7.05 (d, 1H), 7.11-7.18 (m, 2H). m / z (M+H) 548.2 y 550.2. hexanoato de (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4dihidroquinolin-1(2H)-yl)methyl (Example 17, Compuesto 4) The desired product appears as a solid amarillo (3,69g, 87% of yield).1H RMN (CDCI3, 300MHz) δ 0.78 (t, 3H), 1.11-1.28 (m, 4H), 1.40-1.78 (m, 6H), 2.20-2.40 (m, 4H), 2.40-2.60 (m, 6H), 2.73-2.81 (m, 2H), 2.85-3.00 (m, 4H), 3.88-4.00 (m, 2H), 5.75-5.83 (m, 2H), 6.55-6.62 (m, 2H), 7.03-7.12 (m, 2H), 7.20-7.26 (m, 2H). m / z (M+H) 576.4 y 578.4. tetradecanoate of (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4dihydroquinolin-1(2H)-yl)methyl (Example 18, Compound 8) The desired product was isolated as a pale yellow solid (54.3% yield yield).1H NMR (CDCI3, 300MHz) δ 0.87 (t, 3H), 1.07–1.37 (m, 22H), 1.55–1.70 (m, 2H), 1.70–1.90 (m, 4H), 2.34 (t, 2H), (t, 2H), (t, 23H), 2.65-2.78 (m, 6H), 2.82-2.90 (m, 2H), 3.02-3.12 (m, 4H), 3.96 (t, 2H), 5.91 (s, 2H), 6.55-6.62 (m, 2H), 6.92-6.98 (d, 7.05), 1H), 7.11-7.18 (m, 2H). m / z (M+H) 688.4 and 690.4. octanoate of (7-(4-(4-(2,3-dichlorophenyl)piperazin-1 -yl)butoxy)-2-oxo-3,4dihydroquinolin-1(2H)-yl)methyl (Example 19, Compound 5) The desired * product was isolated as a yellow oil (2.2H NH in 17% yield). (CDCI3, 300MHz) δ 0.82 (t, 3H), 1.15-1.35 (m, 10H, 1.55-1.87 (m, 6H), 2.34 (t, 2H), 2.53 (t, 2H), 2.65–2.73 (m, 4H), 2.85 (dd, 2H), 3.01–3.11 (m, 4H), 3.95 (t, 2H), 5.85-5.92 (m, 2H), 2.53-2.60 (m, 2H), 6.91-6.97 (m, 1H), 7.05 (d, 1H), 7.10-7.16 (m, 2H). m / z (M+H) 604.3 y 606.3. 217 Í φ carbonate de (7-(4-(4-(2,3-d¡chlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4| dih¡droquinolin-1(2H)-yl)methylisopropyl (Example 20, Compuesto 48) The product described is listed as an anaranized vinegar (2.4g, 68% efficiency).1H RMN (CDCI3, 300MHz) δ 1.31 (d, 6H), 1.62-1.77 (m, 2H), 1.77- 1.89 (m, 2H), 2.48 (t, 2H), 2.60-2.71 (m, 6H), 2.81-2.90 (m, 2H), 3.01-3.11 (m, 4H), 3.98 (t, 2H), 4.89-4.97 (m, 1H), 5.92 (s, 2H), 6.57 (d, 1H), 6.68 (d, 1H), 6.91-7.00 (m, 1H), 7.05 (dd, 1H), 7.11-7.18 (m, 2H). m / z (M+H) 564.3 y 566.3. methylcarbamate de (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-¡l)butoxy)-2-oxo- 3,4-dihydroquinolin-1(2H)-yl)methyl (Example 21, Compound 47) The desired product was isolated as a yellow solid (1.3 g, 52% yield). 1H NMR (CDCI3, 300 MHz) δ 1.68-1.88 (m, 4H), 2.49 (dd, 2H), 2.60-2.73 (m, 6H), 2.80- 2.90 (m, 5H), 3.02-3.12 (m, 4H), 3.95-4.02 (m, 2H), 5.90 (s, 2H), 6.57 (d, 1H), 6.77 (d, 1H), 6.93-6.70 (m, 1H), 7.05 (d, 1H), 7.10-7.19 (m, 2H). m / z(M+H) 535.5 and 537.5. (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl decylcarbamate (Example 22, Compound 46) The desired product was isolated as a yellow solid (0.50 g, 14% yield). 1H NMR (CDCI3, 300 MHz) δ 0.86 (t, 3H), 1.18-1.35 (m, 16H), 1.42-1.53 ​​(m, 2H), 1.67- 1.79 (m, 2H), 1.79-1.87 (m, 2H), 2.48 (t, 2H), 2.58-2.72 (m, 4H), 2.80-2.90 (m, 2H), 3.01-3.12 (m, 4H), 3.15-3.22 (m, 2H), 3.98 (t, 2H), 4.78 (NH), 5.90 (s, 2H), 6.58 (d, 1H), 6.78 (d, 1H), 6.93-7.00 (m, 1H), 7.04 (d, 1H), 7.10-7.16 (m, 2H). m / z (M+H) 661.6 y 663.6. isobutirato de (7-(4-(4-(2,3-diclorofenil)piperazin-1 -il)butoxi)-2-oxo-3,4dihidroquinolin-1(2H)-¡l)met¡lo (Ejemplo 23, Compuesto 32)1H RMN (CDCb, 300MHz) δ 1.18 (d, 6H), 1.68-1.88 (m, 4H), 2.45-2.73 (m, 9H), 218 2.87 (dd, 2H), 3.03-3.12 (m, 2H), 3.95 (t, 2H), 5.91 (s, 2H), 6.55-6.60 (m, 2H), 6.93-6.97 (m, 1H), 7.04-7.09 (m, 1H), 7.12-7.19 (m, 2H). m / z (M+H) 548,15. ciclopentancarboxilato de (7-(4-(4-(2,3-diclorofenil)piperazin-1 -il)butoxi)-2oxo-3,4-dihidroquinolin-1(2H)-il)metilo (Ejemplo 24, Compuesto 33)1H RMN (CDCh, 300MHz) δ 1.47-1.93 (m, 13H), 2.50-2.60 (m, 2H), 2.60-2.90 (m, 8H), 3.02-3.15 (m, 4H), 3.95 (t, 2H), 5.89 (s, 2H), 6.50-6.60 (m, 2H), 6,906.95 (m, 1H), 7.02-7.07(m, 1H), 7.10-7.19 (m, 2H). m / z (M+H) 574,15. ciclobutancarboxilato de (7-(4-(4-(2,3-diclorofenil)piperazin-1 -il)butoxi)-2oxo-3,4-dihidroquinolin-1(2H)-il)metilo (Ejemplo 25, Compuesto 34)1H RMN (CDCh, 300MHz) δ 1.82-1.91 (m, 3H), 1.22-1.30 (m, 2H), 1.75-2.05 (m, 6H), 2.05-2.40 (m, 6H), 2.68-2.73 (m, 2H), 2.84-2.90 (m, 2H), 3.06-3.22 (m, 4H), 3.96 (t, 2H), 5.91 (s, 2H), 6.55-6.59 (m, 2H), 6.97 (dd, 1H), 7.07 (d, 1H), 7.12-7.18 (m,2H). m / z (M+H) 560,19. cyclohexancarboxylate de (7-(4-(4-(2,3-dichlorophenyl)piperazin-1 -yl)butoxy)-2oxo-3,4-dihydroquinone-1(2H)-1)methyl (Example 26, Compuesto 35) Ή NMR (CDCh, 300MHz) δ 1.15-1.35 (m, 3H), 1.35-1.55 (m, 2H), 1.55-1.95 (m, 10H), 2.21-2.40 (m, 1H), 2.52-2.60 (m, 1H), 2.62-3.00 (m, 8H), 3.02-3.12 (m, 4H), 3.95 (t, 2H), 5.89 (s, 2H), 6.50-6.60 (m, 2H), 6.93-6.97 (m, 1H), 7.027.06 (m, 1H), 7.10-7.15 (m, 2H). m / z (M+H) 588.24. 2-(2-methoxyethoxy)acetate de (7-(4-(4-(2,3-d¡chlorophenyl)piperazin-1-yl)butoxy)2-oxo-3,4-dihidroquinolin-1(2H)-yl)methyl (Ejemplo 27, Compuesto 40) Ή NMR (CDCh, 300MHz) δ 1.56-1.90 (m, 6H), 2.43-2.55 (m, 2H), 2.55-2.80 (m, 4H), 2.81-2.90 (m, 2H), 3.37 (s, 3H), 3.55-3.61 (m, 2H), 3.72-3.79 (m, 2H), 4.20 (s, 2H), 5.97 (s, 2H), 6.55-6.59 (m, 2H), 6.91-6.98 (m, 1H), 7.09 (d, 1H), 7.11-7.15 (m, 2H). m / z (M+H) 594.17. 219 2-(2-(2-metoxietoxi)etoxi)acetato de (7-(4-(4-(2,3-diclorofenil)piperazin-1 il)butoxi)-2-oxo-3,4-dihidroquinolin-1 (2H)-il)metilo (Ejemplo 28, Compuesto 41)1H RMN (CDCI3, 300MHz) δ 1.65-1.93 (m, 6H), 2.49-2.60 (m, 2H), 2.61-2.77 (m, 4H), 2.81-2.90 (m, 2H), 3.02-3.20 (m, 4H), 3.36 (s, 3H), 3.51-3.57 (m, 2H), 3.60-3.70 (m, 4H), 3.72-3.78 (m, 2H), 3.92-3.99 (m, 2H), 4.20 (s, 2H), 5.97 (s, 2H), 6.55-6.59 (m, 2H), 6.95-6.99 (m, 1H), 7.05-7.09 (m, 1H), 7.11-7.18 (m, 2H). m / z (M+H) 638,30. pivalato de (7-(4-(4-(2,3-diclorofenil)piperazin-1-il)butoxi)-2-oxo-3,4dihidroquinolin-1(2H)-il)met¡lo (Ejemplo 29, Compuesto 42)1H RMN (CDCIg, 300MHz) δ 1.21 (s, 9H), 1.65-1.88 (m, 4H), 2.45-2.55 (m, 2H), 2.60-2.73 (m, 6H), 2.82-2.91 (m, 2H), 3.02-3.13 (m, 4H), 3.95 (t, 2H), 5.89 (s, 2H), 6.54-6.60 (m, 2H), 6.92-6.99 (m, 1H), 7.06 (d, 1H), 7.13-7.17 (m, 2H); m / z (ΜΉ) 562,39. (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2oxo-3,4-dihydroquinolin-1(2H)-yl)methyl 2-hydroxyethylcarbamate (Example 30, Compound 36) 2-(((7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2oxo-3,4-dihydroquinolin-1(2H)-yl)methoxy)carbonylamino)ethyl methacrylate (2.0 g) was synthesized similarly to Example 2. This was reacted with 16% NH3 / MeOH at room temperature for 18 hours and then concentrated at 40°C. The residue was purified by silica chromatography by eluting with 1:1:0.1 to 1:1:0.2 DCM / EtOAc / MeOH. The resulting yellow oil was recrystallized from EtOAc / heptane to give the title compound as a white solid (1.2 g, 67%). 1H NMR (CDCI3, 300MHz) δ 1.60-1.88 (m, 4H), 2.40-2.50 (m, 2H), 2.50-2.75 220 c (m, 6H), 2.75-2.89 (m, 2H), 2.95-3.15 (m, 4H), 3.20-3.40 (m, 2H), 2.58-3.78 (m, 2H), 3.89-4.05 (m, 2H), 5.30-5.45 (m, NH), 5.91 (s, 2H), 6.55 (dd, 1H), 6.73 (d, 1H), 6.91-6.96 (m, 1H), 6.98-7.03 (m, 1H), 7.04-7.18 (m, 2H). m / z (M+H) 565.16. (7-(4-(4-(2,3-dichlorophenyl)piperazin-1yl)butoxy)-2-oxo-3,4-dihydroquinolin-1 (2H)-yl)methyl bis(2-hydroxyethyl)carbamate (Example 31, Compound 37) To a solution of hemiaminal A1 (2 g, 0.0042 mol) in dichloromethane (30 mL) at room temperature, pyridine (0.68 mL) was added, followed by p-nitrophenyl chloroformate (1.27 g, 0.0063 mol). After 90 minutes, diethanolamine (3.5 g, 0.0334 mol) and triethylamine (1.2 mL, 0.084 mol) were added. After 3 h, the reaction was diluted with dichloromethane and washed with saturated NaHCO3, dried over MgSCU, and evaporated. The residue was purified over silica by eluting with 1:1:0.1 to 1:1:0.2 DCM / EtOAc / MeOH to give the title compound as a colorless gum (0.83 g, 33%). 1H RMN (CDCI3, 300MHz) δ 1.70-1.82 (m, 4H), 2.42-2.52 (m, 2H), 2.59-2.79 (m, 6H), 2.80-2.90 (m, 2H), 3.00-3.12 (m, 4H), 3.40-3.48 (m, 2H), 3.50-3.58 (m, 2H), 3.61-3.70 (m, 2H), 3.85-3.90 (m, 2H), 3.99-4.06 (m, 2H), 5.90 (m, 2H), 6.57 (d, 1H), 6.70 (dd, 1H), 6.92-6.98 (m, 1H), 7.07 (d, 1H), 7.10-7.20 (m, 2H). m / z (M+H) 609.21. 4-metilpiperazin-1 -carboxilato de (7-(4-(4-(2,3-diclorofenil)piperazin-1- il)butoxi)-2-oxo-3,4-dihidroquinolin-1 (2H)-il)metilo (Ejemplo 32, Compuesto 38) The Compuesto 141 uses similar skills to Ejemplo 28. 1H RMN (CDCI3, 300MHz) δ 1.68-1.88 (m, 4H), 2.25-2.42 (m, 7H), 2.45-2.55 221 (m, 2H), 2.61-2.76 (m, 6H), 2.85 (dd, 2H), 3.02-3.16 (m, 4H), 3.40-3.60 (m, 4H), 3.97 (t, 2H), 5.92 (s, 2H), 6.59 (d, 1H), 6.74 (d, 1H), 6.92-6.98 (m, 1H), 7,027.07 (m, 1H), 7.10-7.16 (m,2H). m / z (M+H) 604.24 1,4'-bipiperidin-1 '-carboxylate of (7-(4-(4-(2,3-d¡clorofenil)piperazin-1 il)butoxi)-2-oxo-3,4-dihidroquinolin-1 (2H)-yl)methyl (Example 33, Compuesto 39) Compuesto 142 is summarized in a similar way to Example 28. 1H NMR (CDCh, 300MHz) δ 1.26-2.06 (m, 14H), 2.31-2.91 (m, 17H), 2.95-3.18 (m, 4H), 3.97 (t, 2H), 4.0-4.37 (m, 2H), 5.91 (s, 2H), 6.58 (dd, 1H), 6.74 (d, 1H), 6.90-6.99 (m, 1H), 7.05 (d, 1H), 7.11-7.18 (m, 2H); m / z (M+H) 672.25. 7-(4-(4-(2,3-dichlorophenyl)piperazin-1 -yl)butoxy)-1-(methoxymethyl)-3,4dihidroquinolin-2(1H)-ona (Ejemplo 34, Compuesto 100) To a mixture of hemiaminal A1 (2.0 g, 4.2 mmol) in dichloromethane (20 mL), thionyl chloride (1.5 mL, 12.6 mmol) was added and stirred for 2 h at room temperature. Methanol (10 mL) was added to the reaction mixture and stirred for another 2 h. The reaction was then transferred to NaHCO3(aq) and extracted with dichloromethane. The organic phase was dried over MgSO4, evaporated, and the residue was purified over silica by eluting with 1:1:0.1 dichloromethane / ethyl acetate / methanol to give the title compound as a cream-colored solid (1.3 g, 63%). 1H NMR (CDCI3, 300MHz) δ 1.65-1.83 (m, 4H), 2.47 (t, 2H), 2.58-2.70 (m, 6H), 2.82 (dd, 2H), 2.99-3.01 (m, 4H), 3.38 (s, 3H), 3.96 (t, 2H), 5.27 (s, 2H), 6.55 (dd, 1H), 6.88 (dd, 1H), 6.91-6.96 (m, 1H), 7.03 (d, 1H), 7.08-7.15 (m, 2H). m / z (M+H) 492.05. 1-(7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4 decanoate 222 dihydroquinolin-1(2H)-yl)-2-ethoxy-2-oxoethyl (Example 35, Compound 111) A mixture of aripiprazole (2.0 g, 4.5 mmol), ethyl glyoxylate (50% solution in toluene, 2.7 mL), K2CO3 (0.49 g, 3.6 mmol), tetrabutylammonium bromide (0.57 g, 1.8 mmol), and dichloromethane (20 mL) was heated under reflux for 4 h. The reaction mixture was cooled and quickly washed with water, dried over MgSCh, and filtered. The resulting solution was treated with pyridine (1.8 mL, 22.2 mmol) and then decanoyl chloride (4.6 mL, 22.2 mmol). After stirring for 3 h, methanol (1 ml) was added and the mixture was stirred for another 10 min. The reaction mixture was washed with saturated NaHCl (aq), dried over MgSO4, and evaporated. The residue was purified over silica by eluting with 1:1:0.1 dichloromethane / ethyl acetate / methanol to give the title compound as a yellow oil (1.2 g, 38%). 1H NMR (CDCI3, 300MHz) δ 0.86 (t, 3H), 1.11 (t, 3H), 1.05-1.40 (m, 12H), 1.591.75 (m, 2H), 1.75-1.98 (m, 4H), 2.40-2.54 (m, 2H), 2.60-3.07 (m, 10H), 3.15- 3.32 (m, 4H), 3.89-3.99 (m, 2H), 4.09-4.21 (m, 2H), 6.57 (dd, 1H), 6.67 (d, 1H), 6.95-7.00 (m, 1H), 7.08 (dd, 1H), 7.12-7.20 (m, 2H), 7.27-7.32 (m, 1H). m / z (M+H) 704.38. (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2oxo-3,4-dihydroquinolin-1(2H)-yl)methyl 4-acetamidobutanoate (Example 36, Compound 44) To a suspension of hemiaminal A1 (2.6 g, 5.5 mmol) in dichloromethane (30 mL), triethylamine (2.3 mL, 16.4 mmol) was added, followed by methanesulfonyl chloride (0.47 g, 6.0 mmol) added over 3 min. The reaction mixture was stirred for 25 min, and then N-acetyl-4-aminobutyric acid (1.6 g, 10.1 mmol) was added. The reaction mixture was then heated under reflux for 18 h, cooled, and washed with saturated NaHCO3 (aq). The organic phase was dried on L 223 MgSO4 was filtered and evaporated. The residue was further purified over silica by eluting with 1:1:0.1 to 1:1:0.2 dichloromethane / ethyl acetate / methanol to give the title compound as an opaque white solid (1.1 g, 34%). 1H NMR (CDCI3, 300MHz) δ 1.70-1.80 (m, 2H), 1.80-1.90 (m, 4H), 1.97 (s, 3H), 2.41 (t, 2H), 2.50-2.57 (m, 2H), 2.60-2.75 (m, 6H), 2.83-2.88 (m, 2H), 3.03-3.12 (m, 4H), 3.24-3.32 (m, 2H), 3.95-4.00 (m, 2H), 5.85-5.92 (m, 3H), 6.58 (d, 2H), 6.92-6.96 (m, 1H), 7.05 (d, 1H), 7.12-7.16 (m, 2H). ). m / z(M+H) 605.08. (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl 4-octanamidobutanoate (Example 37, Compound 45) Compuesto 149 (1.4g) is synthesized similarly to Compuesto 148.1H RMN (de-DMSO, 300MHz) δ 0.79 (t, 3H), 1.10-1.28 (m, 8H), 1.38-1.48 (m, 2H), 1.50-1.77 (m, 6H), 1.93-2.00 (m, 2H), 2.25-2.40 (m, 4H), 2.40-2.60 (m, 6H), 2.72-2.81 (m, 2H), 2.87-3.02 (m, 6H), 3.90-4.00 (m, 2H), 5.82 (s, 2H), 6.58- 6.63 (m, 2H), 7.04-7.02 (m, 2H), 7.20-7.30 (m, 2H). m / z (M+H) 689.47. hexanoato de (5-(2-(4-(benzo[d]isothiazol-3-yl)piperazin-1 -yl)ethyl)-6-cloro-2oxoindolin-1-yl)metilo (Example 38, Compuesto 322) Paraformaldehyde Cat.Zinc chlorrde STEP 1: Thionyl chloride (12.31 g, 103 mmol) was added, followed by a catalytic amount of N,N-dimethylformamide (DMF, 0.1 mL), to a solution of hexanoic acid (10 g, 86 mmol) in dichloromethane (DCM, 100 mL) at 25–30 °C. The reaction solution was stirred at the same temperature for 2 hours under a nitrogen atmosphere until the starting material was consumed, as determined by TLC analysis. The volatile materials were evaporated under reduced pressure below 40 °C, yielding a viscous liquid, hexanoyl chloride. 224 (approximately 10.5 g). STEP 2: To the hexanoyl chloride above, paraformaldehyde (3.8 g, 128 mmol) and anhydrous ZnCl2 (0.232 g, 17 mmol) were added at 25-30 °C under an inert atmosphere and then heated to 90 °C. The thick mass was stirred at 90-95 °C for 5 hours, which after cooling gave the crude product, chloromethyl hexanoate, which was purified by column chromatography on silica gel. 1H-NMR (CDCI3, 500 MHz): δ 5.70 (s, 2H), 2.39-2.33 (m, 2H), 1.69-1.61 (m, 2H), 1.33-1.28 (m, 4H), 0.90-0.88 (t, J=7, 3H). + EITHER STEP 3: Chloromethyl hexanoate (3.18 g, 19.0 mmol) in dichloromethane (6 mL) was added to a freebase suspension of ziprasidone (4.0 g, 9.6 mmol), triethylamine (4.0 mL, 27 mmol), and 4-dimethylaminopyridine (DMAP, 0.708 g, 5 mmol) in methane dichloride (240 mL) at 25–30 °C. The reaction solution was stirred for 24 h at the same temperature. The crude mixture was washed with water (100 mL) followed by brine solution (100 mL), and evaporation of the solvent under vacuum below 40 °C gave the crude titer product, Compound 322, which was further purified by column chromatography on silica gel (1.4 g, 27% yield). 1H-NMR(CDCI3, 500 MHz): δ 7.92-7.90 (d, J=7.5.1H), 7.82-7.80 (d, J=7.5.1H) 225 ,7.48-7.45 (t, J=7.5.1H), 7.37-7.34 (t, J=7.5,1H), 7.17 (s,1H),7.05 (s, 1H), 5.72 (s, 2H), 3.60-3.55 (m, 2H), 3.60-3.55 (m, 2.6t-H), 2.79–2.78 (m, 4H),2.68–2.65 (t, J=8.5, 2H),2.35–2.32 (t, J=7.5.2H), 1.64–1.61 (t, J=7.5, 2H), 1.29–1.88 (t,H0,=J=8. 3H). Mass (m / z) = 541 [M++ 1], dodecanoate of (5-(2-(4-(benzo[d]isothiazol-3-yl)piperazine-1 -yl)ethyl)-6-chloro-2oxondolin-1-yl)methyl (Example 39, Compound 324) Compound 324 was synthesized in a manner similar to Compound 322, Example 38. 1H-RMN(CDCI3, 500 MHz): δ 7.92–7.90 (d, J=7.5, 1H), 7.82–7.80 (d, J=7.5,1H) ,7.48–7.45 (t, J=7.5, 1H), J=7.7,5–H 7.17 (s, 1H),7.05 (s, 1H), 5.72 (s, 2H), 3.60–3.55 (m, 6H), 2.98–2.95 (t, J=8, 2H), 2.79–2.77 (m, 4H),2.68- 2.65 (t, J=8, 2H),2.34-2.31 (t, J=7.2H), 1.63-1.60 (m, ,2H), 1.24(s, 16H), 0.890.86 (t, J=7, 3H). Mass (m / z) = 625.5 [M++ 1], palmitate of (5-(2-(4-(benzo[d]isothiazol-3-yl)piperazine-1 -yl)ethyl)-6-chloro-2oxonondolin-1-yl)methyl (Example 40, Compound M+1H-RM5) 7.92–7.90 (d, J=7.5, 1H), 7.82–7.80 (d, J=7.5, 1H), 7.48–7.45 (t, J=7.5, 1H), 7.37–7.34 (t, J=7.5, 1H), 7.17 (s, 1H), 7.05 (s, 1H), 5.72 (s, 2H), 3.60–3.55 (m, 6H), 2.98–2.95 (t, J=8, 2H), 2.79–2.77 (m, 4H), 2.68- 2.65 (t, J=8, 2H), 2.34–2.31 (t, J=8, 2H), 1.63–1.56 (m, 2H), 1.25–1.23 (m, 24H), 0.88–0.86 (t, J=7, 2H). Mass (m / z) = 681.5 [M++ 1]. acetate of (7-[(4-biphenyl-3ylmethyl)piperazin-1-yl]-2-oxobenzo[d]oxazol-3(2H)yl)methyl 226 (Example 41, Compound 416). Step 1, Synthesis of chloromethyl acetate: Acetyl chloride (5 g, 0.06 mol) was added dropwise to a mixture of paraformaldehyde (8.5 g, 0.06 mol) and anhydrous zinc chloride (0.175 g, 0.02 mol) at 0°C under argon. The reaction mixture was heated to room temperature and stirred for 1 hour, then heated to 90°C for 18 hours. The solid was removed by filtration, washed with dichloromethane, and the filtrate was concentrated under vacuum at 37°C to give the desired product (6.6 g, 94% yield). The product was used directly (without purification) in the next step and stored using activated molecular sieves (4°A). Step 2, Synthesis of iodomethyl acetate: Sodium iodide (27.6 g, 0.18 mol) was added to a solution of chloromethyl acetate (6.6 g, 0.06 mol) in acetonitrile (66 mL). The reaction vessel was covered with aluminum foil to block light and stirred at room temperature for 15 hours. The reaction mixture was partitioned between dichloromethane and water, and the aqueous layer was extracted with dichloromethane. The combined organic materials were washed with saturated aqueous NaHCO3, 10% aqueous sodium sulfite solution, and brine, then dried with sodium sulfate and concentrated to give the product (1.13 g, 12% yield) as a yellow oil. Step 3: n-Butyllithium (1.6 M in hexane; 3.8 mL, 0.007 mol) was added dropwise from a syringe to a stirred solution of bifeprunox (1.46 g, 0.003 mol) in 227 c Tetrahydrofuran was heated at -78°C. After 1 hour, iodomethyl acetate solution (1.13 g, 0.005 mol) was added dropwise at -70°C. The reaction mixture was stirred for 15 hours. The reaction mixture was then poured onto a saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The combined organic layers were washed with 1N NaOH solution and brine, then dried with sodium sulfate and concentrated under vacuum. Purification by flash chromatography gave compound 416. (0.25 g, 14% yield).1H NMR (DMSO, 400MHz) δ 2.034 (s, 3H), 2.565 (s, 4H), 3.183 (s, 4H), 3.597 (s, 2H), 5.765 (s, 2H), 6.696-6.717 (d, 1H), 6.882-6.901 (d, 1H), 7.091-7.182 (t, 1H), 7.315-7.370 (q, 2H), 7.404-7.473 (m, 3H), 7.515-7.555 (d, 1H), 7.59 (d, 1H), 7,639-7,657 (d, 2H). m / z (M+H) 457. (7-[(4-biphenyl-3ylmetii)piperazin-1-yl]-2-oxobenzo[d]oxazol-3(2H)yl)methyl butyrate (Example 42, Compound 417). Compound 417 was prepared similarly to Example 41 using butanoyl chloride. Purification by flash chromatography gave the desired product (1.25 g, 45% yield). 1H NMR (DMSO, 400MHz) δ 1.065 (t, 3H), 1.448-1.54 (m, 2H), 2.284-2.320 (t, 2H), 2.564 (s, 4H), 3.184 (s, 4H), 3.597 (s, 2H), 5.787(s, 2H), 6.694-6.713 (d, 1H), 6.878-6.896 (d, 1H), 7.092-7.133 (t, 1H), 7.315-7.370 (q, 2H), 7.422-7.533 (m, 3H), 7.535-7.555 (d, 1H), 7,639 (d, 1H), 7,657-7,660 (d, 2H). m / z(M+H)485. (7-[(4-biphenyl-3ylmethyl)piperazin-1-yl]-2-oxobenzo[d]oxazol3(2H)-yl)methyl hexanoate (Example 43, Compound 413). Compound 413 was prepared similarly to Example 41 using hexanoyl chloride. Purification by flash chromatography gave the desired product (0.6 g, 60% yield). 1H NMR (DMSO, 400MHz) δ J 228 0.774 (t, 3H), 1,114-1,187 (m, 4H), 1,433-1,506 (m, 2H), 2,291-2,328 (t, 2H), 2,564 (s, 4H), 3,182 (s, 4H), 3,597 (s, 2H), 5,783(s, 2H), 6,693-6,713 (d, 1H), 6,870-6,890 (d, 1H), 7,090-7,130 (t, 1H), 7,314-7,351 (q, 2H), 7,422-7,472 (m, 3H), 7,535-7,554(d, 1H), 7,589(d, 1H), 7,638-7,656 (d, 2H). m / z (M+H)513. palmitato de (7-[(4-bifenil-3ilmetil)piperazin-1-il]-2-oxobenzo[d]oxazol3(2H)-il)metilo (Ejemplo 44, Compuesto 422). Compound 422 was prepared similarly to Example 41 using palmitoyl chloride. Purification by flash chromatography gave the desired product (0.5 g, 47% yield). 1H NMR (DMSO, 400MHz) δ 0.819 (t, 3H), 1.127-1.302 (m, 22H), 1.437-1.454 (t, 2H), 2.287-2.305(t, 2H), 2.564 (s, 4H), 3.182 (s, 4H), 3,596 (s, 2H), 5,784 (s, 2H), 6,688-6,708 (d, 1H), 6,863-6,882 (d, 1H), 7,083-7,124 (t, 1H), 7,331-7,368 (q, 2H), 7,400-7,470 (m, 3H), 7,534-7,553 (d, 1H), 7,587 (d, 1H), 7,635-7,653 (d, 2H). m / z (M+H)653. (7-[(4-biphenyl-3ylmethyl)piperazin-1-yl]-2-oxobenzo[d]oxazol3(2H)-yl)methyl decanoate (Example 45, Compound 419). Compound 419 was prepared similarly to Example 41 using decanoyl chloride. Purification by flash chromatography gave the desired product (0.8 g, 77% yield). 1H NMR (DMSO, 400MHz) δ 0.795-0.829 (t, 3H),1.140-1.211 (m, 12H), 1.438-1.471 (t, 2H), 2.288-2.324(t, 2H), 2.562 (s, 4H), 3.181 (s, 4H), 3.595 (s, 2H), 5.783(s, 2H), 6.689-6.709 (d, 1H), 6.856-6.884 (d, 1H), 7.083-7.124 (t, 1H), 7.311-7.367 (q, 2H), 7.400-7.470 (m, 3H), 7.533-7.552 (d, 1H), 7.587 (d, 1H), 7.635-7.653 (d, 2H). m / z (M+H)569. (7-[(4-biphenyl-3ylmethyl)piperazin-1-yl]-2-oxobenzo[d]oxazol3(2H)-yl)methyl isobutyrate (Example 46, Compound 414). Compound 414 was prepared in a similar manner to Example 41 using 229 isobutyryl chloride. Purification by flash chromatography gave the desired product (0.3 g, 15% yield). 1H NMR (DMSO, 400MHz) δ 1.027-1.044 (d, 6H),2.478-2.553 (m, 1H), 2.562 (s, 4H), 3.185 (s, 4H), 3.597 (s, 2H), 5.785(s, 2H), 6.692-6.713 (d, 1H), 6.873-6.892 (d, 1H), 7.093-7.134 (t, 1H), 7.315-7.369 (q, 2H), 7.403-7.472 (m, 3H), 7.533-7.555 (d, 1H), 7,590 (d, 1H), 7,657-7,660 (d, 2H). m / z (M+H)485. (7-(4-(4-(2,3-dichlorophenyl)p¡perazin-1-yl)butoxy)-2-oxoquinolin1(2H)-yl)methyl butyrate (Example 47, Compound 151). (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4dihydroquinolin-1(2H)-yl)methyl butyrate (Compound 2) was prepared as described in Example DDQ.TFA Compound 2 Compound 151 To a stirred solution of (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl butyrate (3.26 g, 5.94 mmol) in THF (100 mL) was added TFA (2.74 mL, 35.63 mmol) followed by 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ; 7.01 g, 30.88 mmol) in THF (40 mL). The reaction was stirred at room temperature over the weekend. The reaction was stopped with water (100 mL) and then titrated with water (600 mL) and dichloromethane (100 mL). Solid NaHCl (100 g) was added and the mixture was stirred for approximately 30 minutes. Dichloromethane (200 ml) was added and the mixture The 230 was filtered. The collected solid was transferred to a separatory funnel and the layers were separated. The aqueous layer was extracted with dichloromethane (2 x 100 mL) and the combined organic materials were washed with water (3 x 100 mL), brine (100 mL) and dried over MgSO4. After filtration, volatile materials were removed. The crude material was purified by silica chromatography by eluting 0–4% methanol / (1:1 ethyl acetate / dichloromethane). The oil was recrystallized from methanol to give Compound 151 (2.03 g, 3.72 mmol, 63% yield). 1H-NMR (300MHz, CDCI3) δ 7.63 (1H, d), 7.45 (1H, d), 7.19-7.06 (2H, m), 6.99- 6.90 (1H, m), 6.88-6.78 (2H, m), 6.52 (1H, d), 6.33 (2H, s), 4.06 (2H, t), 3.17- 2.99 (4H, bs), 2.74-2.43 (6H, m), 2.35 (2H, t), 1.94-1.54 (6H, m), 0.93 (3H, t). The following compounds were synthesized similarly to Example 47 from their corresponding 3,4 dihydro precursors: (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxoquinolin-1(2H)-yl)methyl palmitate (Example 48, Compound 159) Compound 159 was synthesized similarly to Example 47 from Compound 10. 2.04 g.1H-NMR (400MHz, CDCI3) δ 7.62 (1H, d), 7.44 (1H, d), 7.18-7.10 (2H, m), 6.98-6.91 (1H, m), 6.87-6.80 (2H, m), 6.52 (1H, d), 6.32 (2H, s), 4.05 (2H, t), 3.15-2.99 (4H, bs), 2.74-2.44 (6H, m), 2.35 (2H, t), 1.92-1.83 (2H, m), 1.80-1.68 (2H, m) 1.66-1.55 (2H, m), 1.32-1.14 (24H, m), 0.87 (3H, t). (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxoquinolin1(2H)-yl)methyl laurate (Example 49, Compound 156) Compound 156 was synthesized in a similar manner to Example 47 from Compound 7. 231 1.37 g.1H-RMN (400MHz, CDCI3) δ 7.62 (1H, d), 7.43 (1H, d), 7.17-7.10 (2H, m), 6.96-6.92 (1H, m), 6.87-6.80 (2H, m), 6.51 (1H, d), 6.33 (2H, s), 4.06 (2H, t), 3.12- 3.01 (4H, bs), 2.71-2.59 (4H, bs), 2.50 (2H, t), 2.35 (2H, t), 1.92-1.83 (2H, í m), 1.78-1.69 (2H, m) 1.66-1.55 (2H, m), 1.32-1.16 (16H, m), 0.86 (3H, t). Estearato of (7-(4-(4-(2,3-diclorofenil)piperazin-1-il)butoxi)-2-oxoquinolin1(2H)-il)metilo (Ejemplo 50, Compuesto 160) The Compuesto 160 se sintetizó de manera similar to the Ejemplo 47 a partir del Compuesto 11. 1.38 g1H-RMN (400MHz, CDCI3) δ 7.62 (1H, d), 7.44 (1H, d), 7.17-7.11 (2H, m), 6.97-6.92 (1H, m), 6.87-6.79 (2H, m), 6.51 (1H, d), 6.32 (2H, s), 4.05 (2H, t), 3.13- 3.00 (4H, bs), 2.73-2.58 (4H, bs), 2.50 (2H, t), 2.35 (2H, t), 1.92-1.83 (2H, m), 1.79-1.69 (2H, m) 1.66-1.55 (2H, m), 1.32-1.14 (28H, m), 0.87 (3H, t) (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxoquinolin1(2H)-yl)methyl acetate (Example 51, Compound 150) Compound 150 was synthesized in a similar manner to Example 47 from Compound 1. 1.61 g1H-NMR (300MHz, CDCI3) δ 7.63 (1H, d), 7.45 (1H, d), 7.18-7.11 (2H, m), 6.98-6.92 (1H, m), 6.90-6.80 (2H, m), 6.52 (1H, d), 6.32 (2H, s), 4.07 (2H, t), 3.14- 3.01 (4H, bs), 2.73-2.59 (4H, bs), 2.51 (2H, t), 2.12 (3H, s), 1.95-1.82 (2H, m), 1.82-1.68 (2H, m) (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2oxoquinolin-1(2H)-yl)methyl 2,2-dimethylbutanoate (Example 52, Compound 165) Compound 165 was synthesized in a similar manner to Example 47 from Compound 16. 1.02 g1H-NMR (400MHz, CDCI3) δ 7.61 (1H, d), 7.43 (1H, d), 7.17-7.10 (2H, 232 m), 6.97-6.92 (1H, m), 6.83-6.79 (2H, m), 6.51 (1H, d), 6.31 (2H, s), 4.05 (2H, t), 3.12-3.02 (4H, bs), 2.71-2.60 (4H, bs), 2.50 (2H, t), 1.92-1.83 (2H, m), 1.78-1.68 (2H, m) 1.55 (2H, q), 1.15 (6H, s), 0.81 (3H, t). octanoato de (2-(N-(1-(1-(4-fluorobencil)-1H-benzo[d]imidazol-2il)piperid¡n-4-il)-N-metilamino)-6-oxopirimidin-1 (6H)-il)metilo (Ejemplo 53, Compuesto 704) Octanoyl chloride (10 g, 0.06 mol) was added dropwise to a mixture of paraformaldehyde (8.07 g, 0.06 mol) and anhydrous zinc chloride (0.163 g, 0.0012 mol) at 0 °C under argon. After the addition was complete, the reaction mixture was stirred at 25 °C for 1 hour, and then heated at 90 °C for 16 hours. The solid was removed by filtration and washed with dichloromethane. The filtrate was concentrated under vacuum at 37 °C to give the desired chloromethyl octanoate (9.5 g, 84% yield), which was used directly (without purification) in the next step. This product was stored on activated molecular sieves (4A) to maintain dryness. Sodium iodide (21.7 g, 0.1449 mol) was added to a solution of chloromethyl octanoate (9.5 g, 0.0483 mol) in acetonitrile (100 ml). The container was covered with aluminum foil to block light and stirred at 25°C for 16 hours. 233 The reaction mixture was partitioned between dichloromethane and water; the aqueous layer was further extracted with dichloromethane. The combined organic extracts were washed with saturated aqueous NaHCO3, 10% sodium sulfite solution, and brine, and finally dried with sodium sulfate and concentrated under vacuum to give the product (8.4 g, 71% yield) as a yellow oil. This product was collected in the next step without further purification. Step 3: n-Butyllithium (1.5 M in hexane; 14.6 mL, 0.0042 mol) was added dropwise to a stirred solution of 2-(N-(1-(1-(4-fluorobenzyl)-1H-benzo[d]imidazol-2-yl)piperidin-4-yl)-N-methylamino)pyrimidin-4(3H)-one (Mizolastine, 14.3 g, 0.00696 mol) in tetrahydrofuran (50 mL) at -78 °C. After 1 hour, the reaction mixture was treated dropwise with iodomethyl octanoate (2.5 g, 0.0231 mol) at 234 The reaction mixture was stirred at 25 °C for 16 hours. The reaction mixture was then poured onto ammonium chloride solution and extracted with ethyl acetate. The combined organic materials were washed with aqueous sodium hydroxide (1N) and brine, then dried with sodium sulfate and concentrated under vacuum. Flash chromatography yielded the desired product (0.45 g, 17% yield). 1H NMR (DMSO, 400MHz) δ 0.815 (t, 3H), 1.117-1.235 (m, 10H), 1.474-1.491 (t , 2H), 1.638-1.665 (d, 2H), 1.992-2.010 (m, 2H), 2.292-2.230 (t, 2H), 2.992 (s, 3H), 3.027-3.088 (t, 2H), 3.55-3.62 (t, 2H), 4.625 (s, 1H) 5.311 (s, 2H), 6.040 (s, 2H), 6,110-6,124 (d, 1H), 7,014-7,076 (m, 2H), 7.148-7.253 (m, 5H), 7.4427.460 (d, 1H), 8.187-8.201 (d, 1H). m / z(M+H) 589. (2-(N-(1-(1-(4-fluorobenzyl)-1H-benzorhimidazol-2-yl)piperidin-4-1)-N-methamino)-6-oxopirimidin-1(6H)-yl)methyl laurate (Example 54, Compound 706) Compound 706 was synthesized using a procedure similar to Example 53 using lauroyl chloride. 1H NMR (DMSO, 400MHz) δ 0.791-0.826 (t, 3H),1.134-1.210 (m, 16H), 1.446 (t , 2H), 1.642-1.925 (d, 2H), 1.956-2.008 (m, 2H), 2.266-2.301 (t, 2H), 2.968 (s, 3H), 3.003-3.063 (t, 2H), 3.31-3.62 (t, 2H), 4.625 (s, 1H) 5.286 (s, 2H), 6.015 (s, 2H), 6,085-6,099 (d, 1H), 7,015-7,072 (m, 2H), 7.122-7.215 (m, 5H), 7.4187.436 (d, 1H), 8.159-8.172 (d, 1H). m / z (M+H) 645.5. (5-(4-(2-(5-ethylpyridine-2-yl)ethoxy)benzyl)-2,4-dioxothiazolidine-3-yl)methyl hexanoate (Example 55, Compound 1003) 235 Step 1: Chloromethyl hexanoate was synthesized from hexanoyl chloride in a process similar to that described above in Example 53, step 1. Step 2: Iodomethyl hexanoate was synthesized from chloromethyl hexanoate in a process similar to that described above in Example 53, step 2. Step 3: A solution of pioglitazone (3.0 g, 0.0084 mol) in dimethylformamide was treated with dry K₂CO₃ (3.48 g, 0.0252 mol) at 25 °C. After 40 minutes, a solution of iodomethyl hexanoate (4.29 g, 0.0168 mol) was added dropwise. The reaction mixture was stirred for 15 hours, then poured over water and extracted with ethyl acetate. The combined organic layers were dried with sodium sulfate and concentrated under vacuum. The product was purified by flash chromatography to obtain the desired product (1.9 g, 44% yield). 1H NMR (CDCh, 400MHz) δ 0.86-0.90 (t, 3H), 1.22-1.29 (m, 8H), 1.58-1.62 (t, 2H), 2.27-2.31 (t, 2H), 2.62-2.64 (d, 2H), 3.04-3.099 (q, 1H), 3.21-3.25 (t, 2H), 3.452-3.497 (q, 1H), 4.30-4.34 (t, 2H), 4.46-4.48 (d, 1H),5.513-5.51 (d, 2H), 6.81-6.85 (t, 2H), 7.09-7.11 (d, 2H) ,7.18-7.20 (d,1H),7.46-7.48(q,1H),8.388.39(d,1H) m / z (M+H) 485. 236 (5-(4-(2-(5-ethylpyridin-2-yl)ethoxy)benzyl)-2,4-dioxothiazolidin-3-yl)methyl laurate (Example 56, Compound 1006) Compound 1006 was synthesized using a procedure similar to Example 55 using lauroyl chloride. 1H NMR (CDCh, 400MHz) δ 0.802-0.836 (t, 3H), 1.133-1.171 (t, 4H), 1.1971.235 (d, 15H), 1.308 (s, 1H), 1.419-1.452 (t, 2H), 2,172,254(q, 2H), 2,5332,590 (q, 2H), 3,044-3,118 (m, 3H), 4,251-4,284 (t, 2H), 4,97-5,005 (q, 1H), 5,345-5,413 (q, 2H), 6.82-6.841 (d, 2H), 7.09-7.11 (d, 2H) ,7.23-7.25 (d,1 H),7.53-7.55(q,1 H), 8.33-8.34 (d, 1H) m / z (M+H) 569. (5-(4-(2-(5-ethylpyridin-2-yl)ethoxy)benzyl)-2,4-dioxothiazolidin-3-yl)methyl palmitate (Example 57, Compound 1008) Compound 1008 was synthesized using a procedure similar to Example 55 using palmitoyl chloride. 1H NMR (CDC, 400MHz) δ 0.870 (s, 3H), 1.23-1.26 (t, 27H), 1.57-1.61 (t, 2H),2.27-2.31 (t, 2H), 2.61.265(t, 2H), 3.06-310 (t, 1H), 3.22-3.25 (t, 2H), 3.45- 3.46 (d, 1H), 4.31-4.34 (t, 2H), 4.45-4.49 (q, 1H), 5.487-5.541 (q, 2H),6.83-6.85 (d, 2H), 7.09-7.11 (d, 2H), 7.19-7.26 (t, 1H), 7.47-7.49(q,1H), 8.393-8.397 (d,1H) m / z(M+H)625. (5-(4-(2-(5-ethylpyridin-2-yl)ethoxy)benzyl)-2,4-dioxothiazolidin-3-yl methyl stearate (Example 58, Compound 1009) Compound 1009 was synthesized using a procedure similar to Example 55 using stearoyl chloride. 1H NMR (CDCh, 400MHz) δ 0.874-0.894 (t, 3H), 1.222-1.260 (t, 30H), 1.5701.603 (d, 1H),2.27-2.31 (t, 2H), 2.609-2.266(q, 2H), 3.04-3.10 (q, 1H), 3.20- 3.24 (t, 2H), 3.46-3.50 (q, 1H), 4.302-4.335 (t, 2H), 4.453-4.487 (q, 1H), 5.488 237 5.552 (q, 2H),6.83-6.86 (d, 2H), 7.09-7.11 (d, 2H) ,7.17-7.19 (d, 1H), 7.447.47(d,1H), 8.386-8.391 (d,1H) m / z (M+H) 653. (5-(4-(2-(5-ethylpyridin-2-yl)ethoxy)benzyl)-2,4-dioxothiazolidin-3-yl)methyl myristoate (Example 59, Compound 1007) Compound 1007 was synthesized using a procedure similar to Example 55 using myristoyl chloride. 1H NMR (CDCh, 400MHz) δ 0.854-0.887 (t, 3H), 1.226-1.262 (t, 24H), 1,571.604 (t, 2H),2.27-2.308 (t, 2H), 2.609-2.265(t, 2H), 3.035-3.094 (q, 1H), 3.2233.256 (t, 2H), 3.456-3.500 (q, 1H), 4.307-4.340 (t, 2H), 4.463-4.487 (t, 1H), 5.487-5.540 (q, 2H),6.832-6.852 (d, 2H), 7.092-7.114 (d, 2H) ,7.198-7.217 (d, 1H), 7.475-7.491 (d,1H), 8.393-8.397 (d,1H) m / z(M+H) 596. (5-(4-(2-(5-ethylpyridin-2-yl)ethoxy)benzyl)-2,4-dioxothiazolidin-3-yl)methyl butyrate (Example 60, Compound 1002) Compound 1002 was synthesized using a procedure similar to Example 55 using butyroyl chloride. 1H NMR (CDCh, 400MHz) δ 0.798-0.835 (t, 3H), 1.133-1.212 (q, 4H), 1.4171.509 (m, 2H), 2.210-2.246 (t, 2H), 2.482-2.2591 (q, 2H), 3.047-3.118 (q, 3H), 4.253-4.286 (t, 2H), 4.983-5.016 (q, 1H), 5.353-5.415 (q, 2H), 6.824-6.845 (d, 2H), 7.097-7.118 (d, 2H) ,7.239-7.258 (d, 1H), 7.538-7.563 (d,1H), 8.340-8.365 (d,1H) m / z(M+H)458. (5-(4-(2-(5-ethylpyridin-2-yl)ethoxy)benzyl)-2,4-dioxothiazolidin-3-yl)methyl cyclohexanecarboxylate (Example 60, Compound 1015) Compound 1015 was synthesized using a procedure similar to the Example using cyclohexanecarbonyl chloride. 1H NMR (CDCI3, 400MHz) δ 1.181-1.293 (m, 7H), 1.359-1.449 (m, 2H), 2.624 238 (s, 1H), 1.714–1.738 (t, 2H), 1.843-1.874(q,2H),2.244-2.319(m,1H),2.6072.664(q,2H),3.049-3.107(q,1H),3.22.-3.253(t,2H),3.340-3.485(q,48),5.5. 2H), 6.831-6.853 (d, 2H), 7.091-7.113 (d, 2H) ,7.193-7.213 (d, 1H), 7.465-7.590 (q,1 H), 8.392-8.396 m / z (d,1 H) (497ΉΉ). General Scheme of Synthesis AgCO3, 2-Me THF i carbonate of ((7-(4-(4-(2,3-dichlorophenyl)piperaz¡n-1 -yl)butoxy)guinolin-2¡Doxymethylhexyl (Example 61, Compound 1240) To a solution of dehydro-aripiprazole (1.5 g, 3.36 mmol) in 2-methyltetrahydrofuran (30 mL), silver carbonate (1.853 g, 6.72 mmol) and hexyliodomethyl carbonate (2.021 g, 7.05 mmol) in 2-methyltetrahydrofuran (4 mL) were added at room temperature. The reaction was stirred for 4.5 days. The reaction was stopped with H₂O (30 mL) and filtered through Celite. The reaction was extracted with ethyl acetate (3 x 20 mL), washed with brine (20 mL), dried over MgSC₄, and concentrated. The product was purified by column chromatography on silica by eluting with 1:1 ethyl acetate to dichloromethane at 2% MeOH in 1:1 ethyl acetate to dichloromethane to give Compound 1240 (1.08 g) as a yellow oil. 1H-NMR (300 MHz, CDCI3) δ 7.96 (1H, d), 7.60 (1H, d), 7.21 (1H, m), 7.14 (2H, m), 7.03 (1H, dd), 6.94 (1H, m), 6.81 (1H, d), 6.26 (2H, s), 4.18 (2H, m), 4.12 (2H, t), 3.09 (4H, m), 2.68 (4H, m), 2.53 (2H, m), 1.91 (2H, m), 1.78 (2H, m), 1.63 (2H, m), 1.28 (6H, m), 0.86 (3H, t). [M+H]+= 604.2. ((7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)quinolin-2E octanoate 239 yl)oxy)methyl (Example 62, Compound 1206) To a solution of dehydro-aripiprazole (1.0 g, 2.24 mmol) in 2-methyltetrahydrofuran (25 mL), silver carbonate (0.864 g, 3.13 mmol) and iodomethyl octanoate (0.764 g, 2.68 mmol) were added at room temperature. The reaction was stirred for 5 days. The reaction was stopped with H₂O (30 mL) and filtered through Celite. The reaction was extracted with ethyl acetate (3 x 20 mL), washed with 5% w / v sodium sulfite solution (15 mL), brine (20 mL), dried over MgSO₄, and concentrated. The product was purified by column chromatography on silica by eluting with 0-70% ethyl acetate in heptane to give Compound 1206 (0.602 g) as a pale orange oil. 1H-RMN (300 MHz, CDCI3) δ 7.95 (1H, d), 7.60 (1H, d), 7.21 (1H, m), 7.14 (2H, m), 7.07 (1H, dd), 6.95 (1H, m), 6.79 (1H, d), 6.24 (2H, s), 4.12 (2H, m), 3.09 (4H, m), 2.68 (4H, m), 2.54 (2H, m), 2.36 (2H, t), 1.90 (2H, m), 1.77 (2H, m), 1.61 (4H, m), 1.23 (6H, m), 0.83 (3H, t). [M+H]+= 602.2. dodecanoato de ((7-(4-(4-(2,3-dichlorophenyl)piperazin-1 -yl)butoxi)quinolin-2yl)oxi)metilo (Example 63, Compuesto 1208) The experimental procedure was carried out in the same way as for the Compuesto-1206 in Example 62, to give 1208 (0.738 g) as an amarillo vinegar. 1H-RMN (300 MHz, CDCI3) δ 7.95 (1H, d), 7.60 (1H, d), 7.20 (1H, d), 7.14 (2H, m), 7.05 (1H, dd), 6.95 (1H, m), 6.80 (1H, d), 6.24 (2H, s), 4.13 (2H, m), 3.09 (4H, m), 2.68 (4H, m), 2.54 (2H, m), 2.36 (2H, t), 1.93 (2H, m), 1.80 (2H, m), 1.60 (4H, m), 1.23 (14H, m), 0.86 (3H, t). [M+H]+= 658.4. butyrate of ((7-(4-(4-(2,3-dichlorophenyl)piperazin-1 -yl)butoxy)quinoline-2240 yl)oxy)methyl (Example 64, Compound 1202) The experimental procedure was carried out in the same way as for Compound-1206 in Example 62, to give 1202 (0.695 g) as a yellow oil. 1H-NMR (300 MHz, CDCh) δ 7.95 (1H, d), 7.61 (1H, d), 7.20 (1H, d), 7.14 (2H, m), 7.04 (1H, dd), 6.96 (1H, m), 6.79 (1H, d), 4.1H, 4.3 s (2H, m), 3.09 (4H, m), 2.69 (4H, m), 2.54 (2H, m), 2.35 (2H, t), 1.91 (2H, m), 1.78 (2H, m), 1.66 (2H, m), 0.94 (3H, t). [M+H]+= 546.1. Example 65: 2^2-dimethyltetradecanoate of ((7-(4-(4-(2,3dichlorophenyl)piperazin-1-yl)butoxy)quinolin-2-yl)oxy)methyl (Compound 1213) and 2,2-dimethyltetradecanoate of (7-(4-(4-(2,3-dichlorophenyl)piperazin-1yl)butoxy)-2-oxoguinolin-1(2H)-yl)methyl (Compound 255) The experimental procedure was carried out in the same way as for Compound-1206 in Example 62 to give Compound-255 and Compound-1212. Compound-1213 was isolated (0.586 g) as a yellow oil, and Compound-255 was isolated (0.156 g) as a yellow oil. Compound-1213:1H-NMR (300 MHz, CDCh) δ 7.93 (1H, d), 7.59 (1H, d), 7.16 (3H, m), 7.03 (1H, dd), 6.97 (1H, m), 6.78 (1H, d), 6.22 (2H, s), 4.12 (2H, m), 3.10 (4H, m), 2.73 (4H, m), 2.57 (2H, t), 1.91 (2H, m), 1.80 (2H, m), 1.46 (2H, d), 1.01 - 1.33 (26H, m), 0.87 (3H, t). [M+H]+= 714.3. Compound-255:1H-NMR (300 MHz, CDCh) δ 7.60 (1H, d), 7.42 (1H, d), 7.15 (2H, m), 6.96 (1H, m), 6.82 (2H, m), 6.51 (1H, d), 6.32 (2H, s), 4.04 (2H, t), 3.07 (4H, m), 2.66 (4H, m), 2.49 (2H, m), 1.87 (2H, m), 1.76 (2H, m), 1.45 (2H, m), 1.01 - 1.36 (26H, m), 0.87 (3H, t). [M+H]+= 714.3. ((7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)quinolin diethylcarbamate241 2-yl)oxy)methyl (Example 66, Compound 1247) The experimental procedure was carried out in the same manner as for Compound-1206 in Example-62. The reaction was incomplete after 5 days at room temperature. The reaction was heated to 60 °C for two days before undergoing the same post-treatment and purification procedure as in Example-62 to give Compound-1247 (0.053 g) as a yellow oil. 1H-NMR (300 MHz, CDCh) δ 7.94 (1H, d), 7.60 (1H, d), 7.20 (1H, m), 7.15 (2H, m), 7.04 (1H, dd), 6.95 (1H, m), 6.81 (1H, d), 6.24 (2H, s), 4.11 (2H, m), 3.28 (4H, m), 3.09 (4H, m), 2.70 (4H, m), 2.54 (2H, m), 1.90 (2H, m), 1.78 (2H, m), 1.13 (3H, q), 1.03 (3H, q). [M+H]+= 575.2. ((7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)quinolin-2yl)oxy)methyl pivalate (Example 67, Compound 1215) The experimental procedure was carried out in the same manner as for Compound-1206 in Example-62 to give Compound 1215 (0.555 g) as a yellow oil. 1H-NMR (300 MHz, CDCh) δ 7.95 (1H, d), 7.60 (1H, d), 7.15 (3H, m), 7.05 (1H, dd), 6.97 (1H, m), 6.79 (1H, d), 6.22 (2H, s), 4.12 (2H, m), 3.10 (4H, m), 2.68 (4H, m), 2.54 (2H, m), 1.91 (2H, m), 1.78 (2H, m), 1.19 (9H, s). [M+H]+= 560.1. Example 68: Pharmacokinetic evaluation in rats Pharmacokinetic evaluation of prodroqas in rats after intramuscular injection Animals: Male Sprague-Dawley rats were obtained (Charles River Laboratories, Wilmington, MA). Approximately 24 rats were used in each study. The rats weighed approximately 350–375 g upon arrival. 242 Rats were housed two to a cage with food and water available ad libitum. Environmental conditions in the housing room were: 64–67°F, 30–70% relative humidity, and a 12:12-h light:dark cycle. All experiments were approved by the Institutional Animal Care and Use Committee. Pharmacokinetic study: Rats were dosed intramuscularly via a 25-gauge catheter. Using a 5 / 8-inch needle and a 1 mL syringe, 0.3 mL of suspension was withdrawn from the ampoule containing the test compound (see Table E). Mice were injected into the hind limb muscles after anesthesia with isoflurane. Blood samples were collected from the lateral tail vein after brief anesthesia with isoflurane. A 27%G needle and a 1 mL syringe without anticoagulant were used for blood sampling. Approximately 350 pL of whole blood were collected at each sampling time point: 6 hours, 24 hours, and 2, 5, 7, 9, 12, 14, 21, 28, and 35 days post-administration. Once collected, the whole blood was immediately transferred to tubes containing K2 EDTA, inverted 10-15 times and immediately placed on ice.The tubes were centrifuged for 2 minutes at >14,000 g (11,500 RPM using an Eppendorf 5417C centrifuge with an F45-30-11 rotor) at room temperature to separate the plasma. The plasma samples were transferred to labeled single tubes (Microtainer®) and stored frozen at <-70°C. Data analysis: Drug concentrations in plasma samples were analyzed by liquid chromatography-mass spectrometry using parameters appropriate for each compound. Half-life, volume of distribution, elimination, maximum concentration, and AUC were calculated using WinNonlin Version 5.2 software (Pharsight, St. Louis, MO). 243 Results and Exposure: The results are shown in Table J. As shown in Table J, each of the compounds tested gave a longer plasma concentration compared to the parent drug when administered alone. Table J Excipient Form Dose AUCo-14 AUCq-t API used (Compound or No.) **(mg / kg) (ng*day / ml) (ng*day / ml) 82 Ethyl oleate solution 57 204 NC 2 Recrystallized crystalline suspension in 1% HPMC in PBS + 0.2% Tween 20 67 1016.9 1139.8 81 Ethyl oleate solution 56 584 NC 48 Milled crystalline suspension in 1% HPMC in PBS + 0.2% Tween 20. Measured and diluted to correct concentration* 70.00 2238 2264.6 5 Ethyl oleate emulsion in water with 67 1728.6 1742 Ί 244 DPPC, Glycerol and NCOH 6 Solution in ethyl oleate 67 67 327 6 Oil-in-water emulsion with DPPC and Glycerol 67 1490.3 1678.1 47 Ground crystalline suspension in 1% HPMC 100.0 113 176 85 Ground crystalline suspension in 1% HPMC in PBS + Tween 20 at 0.2%. Measured and diluted to correct concentration 67 1233.9 1348 1 Crystalline material suspended in 1% HPMC 56.7 1673 1938 7 Recrystallized crystalline suspension in 1% HPMC in 0.2% PBS + Tween 20 67 512.0 1169.5 32 Ground crystalline suspension in 67% HPMC 1334.4 1486 245 % in PBS + 0.2% Tween. Measured and diluted to correct concentration* Ground crystalline suspension in 1% HPMC in PBS + 0.2% Tween 20 Ground crystalline suspension in 1% HPMC 24 580.3 666.1 73.3 152 199.7 Ground crystalline suspension in 1% HPMC in PBS + 0.2% Tween. Measured and diluted to correct concentration* Prodrug solution in ethyl oleate Recrystallized crystalline suspension in 43.33 2050 2095.8 67 954 NC 67 907.4 940 1% HPMC in PBS + 0.2% Tween 20 246 Φ 31 Recrystallized crystalline suspension in 1% HPMC in PBS + 0.2% Tween 20 67 819.0 997 10 Recrystallized crystalline suspension in 1% HPMC in PBS + 0.2% Tween 20 67 302 786.6 4 Recrystallized crystalline suspension in 1% HPMC in PBS + 0.2% Tween 20 67 1455.4 1678 1002 Crystalline material in 2% CMC, 0.2% Tween 20, PBS pH buffer solution 302 mOsm / Kg, pH 6.7 67 5350 5972 1008 Crystalline material in 2% CMC, 0.2% Tween 20, PBS pH buffer solution 302 mOsm / Kg, pH 6.7 67 5000 6763 247 Example 69: Pharmacokinetic study for ploklitazone. Compounds 1002 and 1008 The pharmacokinetic (PK) profile of Compounds 1002 and 1008 was compared with that of pioglitazone using a model similar to the one described above. 20 mg of pioglitazone or a prodrug equivalent of 20 mg of pioglitazone was administered intramuscularly. The results are given in Table J, above. Figure 10 shows the PK profile and its comparison with pioglitazone. Example 70 - Pharmacodynamic studies using an amphetamine-induced locomotion model Introduction: The prodrugs of the invention, which are useful in the treatment of schizophrenia and bipolar disorder, show predictive validity in rodent hyperlocomotion models. Danfetamine-induced locomotion is postulated as a mimetic of the dopaminergic hyperactivity upon which the “dopamine hypothesis” of schizophrenia is based. The AMPH-induced hyperactivity model provides a simple initial study of the compound’s antipsychotic efficacy. See Fe et al., Journal of Pharmacology and Experimental Therapeutics (2008) 326:209-217. Amphetamine-induced hyperactivity was used to study various doses of orally administered (po) aripiprazole prodrug formulations to measure pharmacodynamic efficacy in an acute hyperlocomotion paradigm.The hypothesis of the study is that oral administration of aripiprazole prodrug formulations, resulting in plasma concentrations of -100-200 ng / ml, will produce a significant attenuation of induced locomotion. 248 AMPH. General behavior and activity can be measured in experimental animals (typically rats and mice) to evaluate a drug's stimulant psychomotor, anxiogenic / anxiolytic, or sedative properties. As such, open-field studies can provide insight into the behavioral effects of test compounds. Certain prodrugs of the present invention are useful in the treatment of schizophrenia and bipolar disorder. Aripiprazole is a lactam-containing parent drug from which some of the prodrugs of the invention, useful in the treatment of schizophrenia and bipolar disorder, are derived. Such aripiprazole prodrugs of the invention show predictive validity in rodent hyperlocomotion models. Danfetamine-induced locomotion is postulated to mimic the dopaminergic hyperactivity upon which the "dopamine hypothesis" of schizophrenia is based.Similarly, it is postulated that locomotion induced by NMDA glutamate receptor antagonists (MK-801, PCP, etc.) mimics the NMDA hypoactive schizophrenia hypothesis (Fell et al., supra). Such drug-induced hyperactivity tests provide simple initial studies of the compound's antipsychotic efficacy. Amphetamine-induced hyperactivity will be used to study various aripiprazole prodrugs, administered orally in oil solutions, to measure pharmacodynamic efficacy. The D-AMPH-induced locomotion results obtained in this study will be compared with historical results of subcutaneous (SC) aripiprazole administration in D-AMPH. The study hypothesis is that oral exposure to aripiprazole will induce locomotion. 249 Aripiprazole prodrugs, which result in aripiprazole concentrations of 100-200ng / ml in locomotor tests, will show in-vivo measures of antipsychotic efficacy. Materials: Experimental animals: Twelve Sprague Dawley rats were acquired from the Charles River Laboratory. The rats were approximately 90 days old and weighed between 275 and 350 grams when received from the supplier. The rats were placed one per cage and allowed to acclimate for approximately one week. Food and water were provided ad libitum. D-amphetamine solution (D-AMPH) dosage: D-AMPH was purchased from Sigma Aldrich. D-amphetamine HCl was prepared in 0.9% saline solution at a concentration of 1.5 mg / mL. D-amphetamine was administered intraperitoneally (IP) at a body weight dose of 1 mL / kg (= 1.5 mg / kg). No saline correction was used, in accordance with historical literature. D-AMPH was prepared from the solid form 30 minutes before each test period. Table K: Solutions for dosing aripiprazole-derived prodrug Formulation Group (Route) Dose Study volume mg / rat dose N mi Compound 7 oral 7.5 oil solution (PO) Oral compound 4 1.5 4 1.5 oil solution 250 (PO) c Compound 4 oral solution in oil (PO) 10 1.5 4 D Compound 7 oral solution in oil (PO) 10 1.5 4 E Compound 4 oral solution in oil (PO) 0.66 1.5 4 F Compound 7 oral solution in oil (PO) 20 1.5 4 G Saline solution (PO) 0 1.5 4 Behavioral chamber: The behavioral chambers are They acquired from Med Associates, Inc. of St. Albans, VT, Model ENV-515. The software for measuring animal movement is provided by the supplier along with the behavioral camera. Methods: After 1 week of habituation to the animal facilities, activity assessments began. The animals were initially acclimated to the behavior box for approximately 15 minutes before being removed from the box and injected orally with 1.5 ml of an ariplprazole prodrug compound of the invention, at concentrations that produced PK levels of 100-200 ng / ml 251 Approximately 1 hour after administration, the animals were returned to the behavioral box for an additional 30-minute baseline test session. D-AMPH (1.5 mg / kg) was then administered to the mice via intraperitoneal injection, followed by a 60-minute behavioral measurement period. The parameters measured were: a) total distance traveled (primary measure), b) total number of ambulatory movements (secondary measure), c) total number of vertical movements (secondary measure), and d) time spent immobile (secondary measure). Blood sampling: Blood was drawn from the tail vein on the days of the experiment immediately following locomotor activity measurements (2 hours post-prodrug administration) and again the following day at a time point corresponding to 22 hours post-prodrug administration. Blood samples were collected from the lateral tail vein after isoflurane anesthesia. A 27.5 G syringe without anticoagulant was used to collect the blood samples, and the whole blood was transferred to pre-chilled (moist ice) tubes containing K2 EDTA. 0.5 ml of blood was collected per animal at each time point. The tubes were inverted 15–20 times and immediately returned to moist ice until centrifuged for 2 minutes at >14,000 g to separate the plasma. Plasma samples prepared in this way were transferred to labeled single tubes (MICROTAINER®) and stored frozen at < -70°C. Acquisition of behavioral data: Behavioral data was captured electronically using the software package associated with 252 Behavioral cameras. Data were transformed and analyzed using GraphPad PRISM® 5 software (GraphPad Software, Inc., La Jolla, CA). Data were analyzed using a 2-way repeated measures ANOVA. Results and Presentation: The results are shown in Figures 6 and 7. The results indicate that orally administered D-AMPH caused a significant increase in the total distance traveled by mice compared to mice administered saline solution alone. The results also indicate that compound 4, an aripiprazole prodrug of the invention, significantly inhibited the increases in distance traveled caused by D-AMPH. The inhibition of distance traveled caused by compound 4 did not appear to be dose-dependent. Similarly, the aripiprazole prodrug compounds 7 and 47 appeared to significantly inhibit the increases in distance traveled caused by D-AMPH at the dose above 20 mg.These data indicate that, according to the invention, the prodrug compounds are cleaved in vivo to release the source drug (aripiprazole in this example) to produce the expected pharmacological effects in the animal. The patents and scientific literature referenced herein constitute the knowledge available to those skilled in the art. All published and unpublished U.S. patents and U.S. patent applications cited herein are incorporated by reference. All published foreign patents and foreign patent applications cited herein are incorporated by reference. All other published references, documents, manuscripts, and scientific literature cited herein are 253 incorporated here by reference. Although the present invention has been shown and described in particular with reference to preferred embodiments thereof, those skilled in the art will understand that various changes in form and detail may be made to it without departing from the scope of the invention covered by the appended claims.

Claims

1. A compound, characterized in that it has the formula: (FORMULA 1) or a pharmaceutically acceptable salt thereof. Sole Claim