MX2008009682A - Aminophthalazine derivative compounds - Google Patents

Abstract

The invention pertains to new aminophthalazine compounds that serve as effective phosphodiesterase (PDE) inhibitors. The invention also relates to. compounds that are selective inhibitors of PDE-10. The invention further relates to intermediates for preparation of such compounds;pharmaceutical compositions comprising such compounds;and the use of such compounds in methods for treating certain central nervous system (CNS) or other disorders, The invention relates also to methods for treating neurodegenerative and psychiatric disorders, for example psychosis and disorders comprising deficient cognition as a symptom. The claimed compounds have following structure:or a pharmaceutically acceptable salt thereof, wherein ring A is a 5 or 6 membered heterocyclic ring substituted or not.

Description

COMPOUNDS DERIVED FROM AMINOFTALAZI NA FIELD OF THE INVENTION The invention pertains to new aminophthalazine compounds which serve as effective inhibitors of phosphodiesterase (PDE). The invention also relates to compounds that are selective inhibitors of PDE-10. The invention further relates to intermediates for the preparation of such compounds, pharmaceutical compositions comprising such compounds; and the use of such compounds in methods for treating certain disorders of the central nervous system (CNS) or others. The invention also relates to methods for treating neurodegenerative and psychiatric disorders, for example, psychoses and disorders comprising deficient cognition as a symptom.

BACKGROUND OF THE INVENTION Phosphodiesterases (PDE) are a class of intracellular enzymes involved in the hydrolysis of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) nucleotides in their respective nucleotide monophosphates. The cyclic nucleotides cAMP and cGMP are synthesized by adenylyl and guanylyl cyclase respectively, and serve as secondary messengers in several cellular routes.

CAMP and cGMP function as second intracellular messengers regulating a wide array of intracellular processes, particularly in the neurons of the central nervous system. In neurons, this includes the activation of cAMP-dependent and cGMP-dependent kinases and subsequent phosphorylation of the proteins involved in the acute regulation of synaptic transmission as well as in neuronal differentiation and survival. The complexity of the cyclic nucleotide signaling is indicated by the molecular diversity of the enzymes involved in the synthesis and degradation of cAMP and cAMP. There are at least ten families of adenylyl cyclase, two of guanylyl cyclase and eleven of phosphodiesterases. In addition, different types of neurons expressing multiple isoenzymes of each of these classes are known, and there is good evidence for the formation of compartments and specificity of the function of different isoenzymes within a given neuron. A major mechanism for regulating the signaling of cyclic nucleotides is by the catabolism of cyclic nucleotides catalyzed by phosphodiesterases. There are 11 known PDE families encoded by 11 different genes. Each gene typically produces multiple splice variants that also contribute to the diversity of isoenzymes. PDE families are functionally distinguished based on the specificity of the cyclic nucleotide substrate, regulatory mechanism (s), and sensitivity to inhibitors. In addition, PDEs are differentially expressed throughout the body, including the central nervous system. As As a result of these different enzymatic activities and locations, the different PDE isoenzymes can serve different physiological functions. In addition, compounds that can selectively inhibit the different PDE families or isoenzymes may offer particular therapeutic effects, fewer side effects, or both. PDE10 is identified as a single family based on the main amino acid sequence and the different enzymatic activity. The homology selection of the EST database revealed mouse PDE10A as the first member of the PDE family (Fujishige et al., J. Biol. Chem. 274: 18438-18445, 1999; Loughney, K. et al., Gene 234: 109-1,17, 1999). The murine homologue has also been cloned (Soderling, S. et al., Proc. Nati, Acad. Sci. USA 96: 7071-7076, 1999) and N-terminal splice variants of both rat and human genes have been identified. (Kotera, J. et al., Biochem Biophys, Res. Comm. 261: 551-557, 1999; Fujishige, K. et al., Eur. J. Biochem. 266: 11-18-1,127, 1999). There is a high degree of homology between the species. Mouse PDE10A1 is a 779 amino acid protein that hydrolyzes both cAMP and cGMP to AMP and GMP, respectively. The affinity of PDE10 for cAMP (Km = 0.05 μ?) Is higher than for cGMP (Km = 3 μ?). However, the approximately 5-fold higher Vmax for cAMP on cAMP has led to the suggestion that PDE10 is a unique GMP-asa inhibited by cAMP (Fujishige et al., J. Biol. Chem. 274: 18438-18445, 1999 ). PDE10 is also uniquely located in mammals in relation to other PDE families. The mRNA for PDE10 is highly expressed only in testes and brain (Fujishige, K. et al., Eur J Biochem 266: 1 1 18-1127, 1999; Soderling, S. et al., Proc. Nati. Acad. Sci. 96: 7071-7076, 1999; Loughney, K. et al., Gene 234: 109-17,1999). These initial studies indicated that within the brain the expression of PDE10 is maximal in the striatum (caudate and putamen), n. Accumbens, and olfactory tubercle. More recently, a detailed analysis of the expression pattern in the brain of rodents of PDE10 mRNA (Seeger, TF et al., Abst. Soc. Neurosci. 26: 345.10, 2000) and the PDE10 protein (Menniti, FS, Stick, CA, Seeger, TF, and Ryan, AM, Immunohistochemical localization of PDE10 in the mouse brain, William Harvey Research Conference 'Phosphodiesterase in Health and Disease', Porto, Portugal, December 5-7, 2001). The publication of the application of US Pat. No. 2003/0032579 describes a method for treating certain neurological and psychiatric disorders with the selective inhibitor of PDE10 papaverine. In particular, the method relates to psychotic disorders such as schizophrenia, hallucinatory disorders and drug-induced psychosis; to anxiety disorders such as panic and obsessive-compulsive disorder; and to movement disorders including Parkinson's disease and Huntington's disease. In its role as second messengers in episodes of intracellular signaling, cAMP and cGMP affect a broad series of processes that include neurotransmission and activation of enzymes. The intracellular levels of these chemical agents are largely maintained by two classes of enzymes in response to other cellular stimuli. The first of these enzymes, adenylyl and guanylyl cyclase, catalyze the formation of cAMP and cGMP, thus increasing their concentrations and activating certain signaling episodes. The second class of enzymes, phosphodiesterases (PDE), catalyzes the degradation of cAMP and cGMP, which results in the termination of the signal. Increasing the signal by raising the cyclic nucleotide concentration can be induced by the use of PDE inhibitors. The present invention describes the use of such inhibitors of PDEs as therapies for the prevention or treatment of diseases linked to abnormal cell signaling processes, and refers to compounds described below.

BRIEF DESCRIPTION OF THE INVENTION The invention relates to compounds having the following formula, referred to herein as Formula I: or a pharmaceutically acceptable salt thereof, wherein ring A is a 5- or 6-membered heterocyclic ring substituted by at least one R6 and at least one R7; wherein R, R2 and R5 are each independently H, halogen, -CN, -COOH, -COOR3, -CONR3R4, -COR20, -NR3R4, -NHCOR20, - OH, aryl (C6-Cio), heteroanal of (5-10) members, alkyl (Ci-C6), haloalkyl (C1-C6) (C2-C6) alkenyl, (C2-C6) alkynyl, (C-i-Ce) alkoxy, (C2-C6) alkenyloxy or (C3-C8) cycloalkyl; or, when R1. R2 and R5 are independently alkoxy (Ci-C6), alkenyloxy (C2-C6), alkyl (C- | -C6), alkenyl (C2-C6) or alkynyl (C2-C6), R1 and R2 or R1 and R5 can be optionally connected forming a ring of 5 to 8 members; wherein R3 and R4 are each independently H, alkyl (CrC6) heteroaryl (5-10 members) or aryl (C6-Cio), said heteroaryl or aryl being optionally substituted with one or more alkyl groups (CrC6) ) or halo; wherein each R6 is independently H, halogen, -COOR3, -CONR3R4, -COR20, -NR3R4, -OH, hydroxyalkyl (Ci-C6) -HNCOOR3, -CN, - HNCONHR4, (C6) alkyl, (Ci-C6) alkoxy, (C6-C10) aryl, -O-alkylene (C6) -heteroaryl (5-8 members), -O-alkylene (-C6) aryl (Ce-C- ??), -alkylene (CrC6) -0-heteraoaryl (5-8 membered), -alkylene (d-C6) -O-aryl (C6-Ci0) or wherein n is 0 or 1; W is carbon, oxygen or NR, where R is hydrogen or alkyl (Cr Ce), and when W is carbon, it may be optionally substituted with halogen, -CN, -COOH, -COOR3, -CONR3R4, -COR20, - NR3R4, -NHCOR20, -OH, aryl (C6-Ci0), heteroaryl (5-10 members), alkyl (C6), haloalkyl (CrC6) alkenyl (C2-C6), alkynyl (C2-C6), alkyloxy ( CrC6), (C2-C6) alkenyloxy or (C3-C8) cycloalkyl; and wherein said alkyl, aryl or heteroaryl of R6 may be optionally substituted with alkyl (C Ce), cycloalkyl (C3-C8), alkoxy (Cs), halogen, -OH, and haloalkyl (CrC8); wherein R9 and R10 are independently hydrogen or alkyl or R9 and R0 can optionally be combined to form a cyclic ring; wherein each R7 is independently R1 1, -R 8 -R1 1 or -OR1; wherein R 1 1 is hydrogen, phenyl, naphthyl, or a heteroaryl ring from 5 to 6 members, optionally condensed to a benzo or heteroaryl ring group, containing one to four heteroatoms selected from oxygen, nitrogen and sulfur, with the proviso that said heteroaryl ring can not contain two adjacent oxygen atoms or two atoms of adjacent sulfur, and wherein each of the following phenyl, naphthyl, heteroaryl, or benzo fused heteroaryl rings may be optionally substituted with one to three substituents independently selected from alkyl (C8), (C3-C8) cycloalkyl, alkoxy (C C8), halogen, -CN, -OH, aryl (C6-Ci0), heteroaryl of (5-10) members, haloalkyl (Ci-Cs), hydroxyalkyl (CrC8), alkoxy (CrC8) -alkyl (C8 ), hydroxycycloalkyl (C3-C8), cycloalkoxy (C3-C8), alkoxy (CrC8) -cycloalkyl (C3-C8), heterocycloalkyl (C3-C8), hydroxyheterocycloalkyl (C3-C8), and alkoxy (Ci-C8) - heterocycloalkyl, in which each e-cycloalkyl or heterocycloalkyl can be independently substituted with one to three halogens, (Ci-C6) alkyl or benzyl groups; or when R1 1 is phenyl, naphthyl, or heteroaryl ring, each ring may be optionally substituted with one to three substituents independently selected from (a) lactone formed from - (CH2) tOH with an ortho -COOH, wherein it is one, two or three; (b) -CONR14R15 or alkylene- (C0-Ce) -NR14R15, wherein R14 and R15 are each independently selected from hydrogen, alkyl (CrC8) and benzyl, or R14 and R5 together with the nitrogen to which are joined together form a heteraoalkyl ring of (5-7) members which may contain from zero to three heteroatoms selected from nitrogen, sulfur and oxygen in addition to the nitrogen of the group -CONR14R15, wherein when each of said heteroatoms is nitrogen it can be optionally substituted with alkyl (C Cs) or benzyl, with the proviso that said ring contains two adjacent oxygen atoms or two sulfur atoms; (c) - (CH2) vNCOR16R17, wherein v is zero, one, two or three and -COR16 and R17 taken together with the nitrogen to which they are attached can form a 4- to 6-membered lactam ring; or when R 11 is heteroaryl, it may optionally be fused to a ring A and optionally substituted with -NR 12 R 13; wherein R12, R13, R16 and R7 are each independently hydrogen, (Ci-C6) alkyl, and (C6-C10) aryl; wherein R18 is (C3) alkylene or -N (R9) - wherein said alkylene may be optionally substituted with alkyl (CrC8), cycloalkyl (C3-C8), alkoxy (CrCs), halogen, -OH , or haloalkyl (CrC8); R19 is hydrogen or (Ci-C6) alkyl; and wherein each R20 is independently alkyl (d-Ce), (C3-C8) cycloalkyl, alkoxy (CrC8), haloalkyl (CrC8), hydroxyalkyl (Ci-C8), alkoxy (Ci-C8) -alkyl (CrC8), hydroxycycloalkyl (C3-C8), cycloalkoxy (C3-C8), alkoxy (C8) -cycloalkyl (C3-C8), heterocycloalkyl (C3-C8), aryl (C6-C-io) or heteroaryl (5-10) members.

DETAILED DESCRIPTION OF THE INVENTION The compounds of Formula I may have optical centers and therefore may exist in different enantiomeric and diastereomeric configurations. The present invention includes all the enantiomers, diastereomers, and other stereoisomers of such compounds of Formula I, as well as racemic compounds and racemic mixtures and other mixtures of stereoisomers thereof. Pharmaceutically acceptable salts of the compounds of Formula I include the acid addition salts and bases thereof. Suitable acid addition salts are formed from acids that form non-toxic salts. Examples include, but are not limited to, the salts acetate, adipate, aspartate, benzoate, besylate, bicarbonate / carbonate, bisulfate / sulfate, borate, camsylate, citrate, cyclamate, edisilate, esylate, formate, fumarate, gluceptate, gluconate, glucuronate, hexafluorophosphate, hybienate, hydrochloride / chloride, hydrobromide / bromide, iodide / iodide, isethionate, lactate, malate, maleate, malonate, mandelates, mesylate, methylsulfate, naphthylate, 2-napsylate, nicotinate, nitrate, orotate, oxalate, palmitate, pamoate, phosphate / acid phosphate / diacid phosphate, pyroglutamate, salicylate, saccharate, stearate, succinate, sulfonate, stannate, tartrate, tosylate, trifluoroacetate and xinofoate. Suitable base salts are formed from bases that form non-toxic salts. Examples include, but are not limited to, salts aluminum, arginine, benzathine, calcium, choline, diethylamine, diolamine, glycine, lysine, magnesium, meglumine, olamine, potassium, sodium, tromethamine and zinc. Hemisal acids and bases can also be formed, for example, the hemisulfate and hemicalcium salts. For a review of suitable salts, see Handbook of Pharmaceutical Salts: Properties, Selection, and Use by Stahl and Wermuth (Wiley - VCH, 2002). The pharmaceutically acceptable salts of the compounds of Formula I can be prepared by one or more of the three methods: (i) by reacting the compound of Formula I with the desired acid or base; (ii) removing an acid or base labile protecting group from a suitable precursor of the compound of Formula I or opening a ring of a suitable cyclic precursor, for example, a lactone or lactam, using the desired acid or base; or (iii) converting one salt of the compound of Formula I to another by reaction with an appropriate acid or base or by a suitable ion exchange column. The three reactions are typically carried out in solution. The resulting salt can be precipitated and collected by filtration or can be recovered by evaporation of the solvent. The degree of ionization in the resulting salt can vary from completely ionized to almost non-ionized. The compounds of the invention may exist in a series continuous of solid states that vary between totally amorphous to totally crystalline. The term 'amorphous' refers to a state in which the material lacks a long-range order at the molecular level and, depending on the temperature, can show the physical properties of a solid or liquid. Typically such materials do not provide distinctive X-ray diffraction patterns and, although they show the properties of a solid, they are more formally described as a liquid. After heating, a change of properties from solid to liquid occurs which is characterized by a change of state, typically of second order ('vitreous transition'). The term 'crystalline' refers to a solid phase in which the material has a regular ordered internal structure at the molecular level and provides a distinctive X-ray diffraction pattern with defined peaks. Such materials when heated sufficiently will also show the properties of a liquid, but the change from solid to liquid is characterized by a phase change, typically of first order ('melting point'). The compounds of the invention can also exist in not solvated and solvated. The term 'solvate' is used in this specification to describe a molecular complex comprising the compound of the invention and one or more pharmaceutically acceptable solvent molecules, for example, ethanol. The term 'hydrate' is used when said solvent is water. A currently accepted classification system for organic hydrates is one that defines isolated site hydrates, channel hydrates, or hydrates coordinated to metal ion - see Polymorphism in Pharmaceutical Solids by K. R. Morris (Ed. H. G. Brittain, Marcel Dekker, 1995). Isolated site hydrates are ones in which the water molecules are isolated from direct contact with each other by intervening organic molecules. In channel hydrates, water molecules are found in reticular channels where they are close to other water molecules. In hydrates coordinated to metal ions, the water molecules are bound to the metal ion. When the solvent or water is tightly bound, the complex will have a well-defined stoichiometry independent of moisture. However, when the solvent or water is weakly bound, as in channel solvates and hygroscopic compounds, the water / solvent content will depend on the humidity and drying conditions. In such cases, non-stoichiometry will be the norm. The compounds of the invention can also exist in a mesomorphic state (mesophase or liquid crystal) when subjected to suitable conditions. The mesomorphic state is intermediate between the true crystalline state and the true liquid state (either molten or in solution). The mesomorphism that arises as a result of a change in temperature is described as 'thermotropic' and that resulting from the addition of a second component, such as water or other solvent, is described as 'lyotropic'. Compounds that have the potential to form lyotropic mesophases are described as 'amphiphilic' and consist of molecules that possess a polar ionic main group (such as -COO ~ Na +, -COO "K +, or -SO3" Na +) or non-ionic (such as -N "N + (CH3) 3) For more information, see Crystals and the Polarizing Microscope by NH Hartshorne and A. Stuart, 4th edition (Edward Arnold, 1970) Hereinafter all references to the compounds of Formula I include references to salts, solvates, multicomponent complexes and liquid crystals thereof and to solvates, multicomponent complexes and liquid crystals of the salts thereof The compounds of the invention include the compounds of Formula I as defined herein above, including all polymorphs and crystalline habits thereof, prodrugs and isomers of the same. (including the optical, geometric and tautomeric isomers thereof) as defined in this specification below and the isotopically-labeled compounds of Formula I. In one embodiment of the present invention, and invention, ring A is piperidine or pyrrolidine. In another embodiment of the present invention, R and R2 are each independently (C1-C4) alkoxy or methoxy. In another embodiment of the present invention, R7 is R and R11 is phenyl optionally substituted with alkoxy (CrC6), (C1-C5) alkyl, -CN, -OH, phenyl or alkoxy (CrC6) substituted with 1 to 3 halogens In another embodiment of the present invention, R7 is -OR11 and R11 is naphthyl or naphthyl substituted with (C-i-C6) alkoxy or (C-i-C6) alkyl. In another embodiment of the present invention, R7 is -OR1 and R11 is 5- or 6-membered heteroaryl. In another embodiment of the present invention, R6 is (d-C6) alkyloxy or -OH. In another embodiment of the present invention, R6 is -NR3R and R3 and R4 are each independently (C1-C3) alkyl. In another embodiment of the present invention, wherein R1 and R2 are each independently alkoxy (CrC6), R7 is R11 and R1 is phenyl or substituted phenyl and R6 is (C6C) alkoxy or -OH. In another embodiment, R6 and R7 can not both be hydrogen. As indicated, the so-called 'prodrugs' of the compounds of Formula I are also within the scope of the invention. Thus certain derivatives of the compounds of Formula I which may have little or no pharmacological activity by themselves may, when administered in the interior or on the body, be converted to compounds of Formula I having the desired activity, for example, by hydrolytic cleavage. Such derivatives are referred to as 'prodrugs'. Additional information on the use of prodrugs can be found in Pro-drugs as Novel Delivery Systems, vol. 14, ACS Symposium Series (T. Higuchi and W. Stella) and Bioreversible Carriers in Drug Design, Pergamon Press, 1987 (Ed. E. B. Roche, American Pharmaceutical Association). The prodrugs according to the invention can be example, producing by replacing appropriate functionalities present in the compounds of Formula I with certain residues known to those skilled in the art as 'pro-residues' as described, for example, in Design of Prodrugs by H. Bundgaard (Elsevier, 1985) . Some examples of prodrugs in accordance with the present invention include, but are not limited to, (i) when the compound of Formula I contains a carboxylic acid functionality (-COOH), an ester thereof, for example, a compound in which the hydrogen of the carboxylic acid functionality of the compound of the formula (I) is replaced by alkyl (Ci-C8); (ii) when the compound of Formula I contains an alcohol functionality (-OH), an ether thereof, for example, a compound in which the hydrogen of the alcohol functionality of the compound of Formula I is replaced by alkanoyl (Ci- C6) oxymethyl; and (ii) when the compound of Formula I contains a primary or secondary amino functionality (-NH2 or -NHR where R? H), an amide thereof, for example, a compound in which, as the case may be, one or both hydrogens of the amino functionality of the compound of Formula I is replaced by alkanoyl (Ci-C10). Additional examples of replacement groups according to the above examples and examples of other types of prodrugs can be found in the aforementioned references. In addition, certain compounds of Formula I can by them they act as prodrugs of other compounds of Formula I. Also included within the scope of the invention are the metabolites of the compounds of Formula I, that is, the compounds formed in vivo after drug administration. Some examples of metabolites according to the invention include, but are not limited to, (i) when the compound of Formula I contains a methyl group, a hydroxymethyl derivative thereof (-CH 3 -> -CH 2 OH); (ii) when the compound of Formula I contains an alkoxy group, a hydroxy derivative thereof (-OR - > -OH); (iii) when the compound of Formula I contains a tertiary amino group, a secondary amino derivative thereof (-NR R2 -> - NHR or -NHR2); (iv) when the compound of Formula I contains a secondary amino group, a primary derivative thereof (-NHR1 -> -NH2): (v) when the compound of Formula I contains a phenyl residue, a phenol derivative thereof ( -Ph - > -PhOH); and (vi) when the compound of Formula I contains an amide group, a carboxylic acid derivative thereof (-CONH2 -> -COOH). Compounds of Formula I containing one or more asymmetric carbon atoms may exist in the form of two or more stereoisomers. When a compound of Formula I contains an alkenyl or alkenylene group, the cis / trans (or Z / E) geometric isomers are possible. When the structural isomers are interconvertible through a low energy barrier, tautomeric isomerism ("tautomería") can be produced. This can take the form of proton tautomerism in compounds of Formula I containing, for example, a methyl group, keto, or oxime, or the so-called valence tautomerism in compounds containing an aromatic moiety. From this it follows that an individual compound can show more than one type of soma. Included within the scope of the present invention are all stereoisomers, geometric isomers and tautomeric forms of the compounds of Formula I, including those compounds that exhibit more than one type of isomerism, and mixtures of one or more thereof. Also included are acid addition salts or bases in which the counterion is optically active, for example, d-lactate or / -Usine, or racemic, for example, d / -tartrate or d / -arginine. The cis / trans isomers can be separated by conventional techniques well known to those skilled in the art, for example, chromatography and fractional crystallization. Conventional techniques for the preparation / isolation of individual enantiomers include chiral synthesis from a suitable optically pure precursor or resolution of the racemate (or the racemate of a salt or derivative) using, for example, chiral high pressure liquid chromatography (HPLC). . Alternatively, the racemate (or a racemic precursor) can be reacted with a suitable optically active compound, by example, an alcohol, or, in the case where the compound of Formula I contains an acid or base moiety, a base or acid such as 1-phenylethylamine or tartaric acid. The resulting diastereomeric mixture can be separated by chromatography and / or fractional crystallization and one or both of the diastereomers can be converted to the corresponding pure enantiomer (s) by means well known to those skilled in the art. The chiral compounds of the invention (and chiral precursors thereof) can be obtained in enantiomerically enriched form using chromatography, typically HPLC, or an asymmetric resin with a mobile phase consisting of a hydrocarbon, typically heptane or hexane, containing between 0 and 50% by volume of isopropanol, typically between 2% and 20%, and between 0 and 5% by volume of an alkylamine, typically 0.1% diethylamine. The concentration of the eluate provides the enriched mixture. When any racemate crystallizes, crystals of two different types are possible. The first type is the racemic compound (true racemate) mentioned above in which a homogeneous crystal form is produced which contains both enantiomers in equimolar amounts. The second type is the racemic or conglomerate mixture in which two crystal forms are produced in equimolar quantities each comprising a single enantiomer. Although both crystalline forms present in a racemic mixture have identical physical properties, they may have different physical properties compared to the true racemate. The racemic mixtures can be separated by conventional techniques known to those skilled in the art - see, for example, Stereochemistry of Organic Compounds by E. L. Eliel and S. H. Wilen (Wiley, 1994). The present invention includes all isotopically-labeled pharmaceutically-acceptable compounds of Formula I in which one or more atoms are replaced by atoms having the same atomic number, but an atomic mass or mass number different from the atomic mass or mass number that predominates in nature. Examples of suitable isotopes for inclusion in the compounds of the invention include, but are not limited to, isotopes of hydrogen, such as 2H and 3H, carbon, such as 1C, 13C and C, chloro, such as 36CI, fluorine, such as 18F, iodine, such as 123l and 125l, nitrogen, such as 13N and 15N, oxygen, such as 15O, 7O and 18O, phosphorus such as 32P, and sulfur, such as 35S. Certain isotopically-labeled compounds of Formula I, for example, those incorporating a radioactive isotope, are useful in drug and / or substrate tissue distribution studies. The radioactive isotopes tritium, i.e., 3H, and carbon-14, i.e. 14C, are particularly useful for this purpose in view of their easy incorporation and easy means of detection. Substitution with heavier isotopes such as deuterium, i.e., 2H, may produce certain therapeutic advantages resulting from increased metabolic stability, for example, increase of half-life in vivo or reduction of dosage requirements, and therefore can Prefer in some circumstances. Substitution with isotopes that emit positrons, such as I I Q i8p I5Q and 13N pUecje be uti | in positron emission tomography (PET) studies to examine the occupation of substrate receptors. The isotopically-labeled compounds of Formula I can be prepared generally by conventional techniques known to those skilled in the art or by methods analogous to those described in the examples and accompanying preparations using an appropriate isotopically-labeled reagent in place of the unlabeled reagent previously employed. The pharmaceutically acceptable solvates according to the invention include those in which the crystallization solvent can be substituted isotopically, for example D20, d6-acetone, d6-DMSO. This invention also relates to a pharmaceutical composition for the treatment of certain psychotic disorders and conditions such as schizophrenia, hallucinatory disorders and drug-induced psychosis; to anxiety disorders such as panic and obsessive-compulsive disorder; and to movement disorders including Parkinson's disease and Huntington's disease, which comprises an amount of a compound of Formula I effective in inhibiting PDE 10. In another embodiment, this invention relates to a pharmaceutical composition for treating disorders and conditions psychotics such as schizophrenia, hallucinatory disorders and drug-induced psychosis; anxiety disorders such as panic and obsessive-compulsive disorder; and movement disorders including Parkinson's disease and Huntington's disease, which comprises an amount of a compound of Formula I in the treatment of said disorder or condition. Examples of psychotic disorders that can be treated in accordance with the present invention include, but are not limited to, schizophrenia, for example of the paranoid, disorganized, catatonic, undifferentiated, or residual type; schizophreniform disorder; schizoaffective disorder, for example of the hallucinatory type or the depressive type; hallucinatory disorder, psychotic disorder induced by substances, for example psychosis induced by alcohol, amphetamine, cannabis, cocaine, hallucinogens, inhalants, opioids, or phencyclidine; Paranoid type personality disorder; and personality disorder of schizoid type. Examples of movement disorders that can be treated in accordance with the present invention include but are not limited to Huntington's disease and dyskinesia associated with dopamine agonist therapy., Parkinson's disease, restless leg syndrome, and essential tremor. Other disorders that can be treated according to the present invention are obsessive / compulsive disorders, Tourette's syndrome and other tic disorders. In another embodiment, the invention relates to a method for treating an anxiety disorder or condition in a mammal, said method comprising administering to said mammal an amount of a compound of formula I effective in inhibiting PDE10. This invention also provides a method for treating an anxiety disorder or condition in a mammal said method comprising administering to said mammal an amount of a compound of Formula I effective in the treatment of such disorder or condition. Examples of anxiety disorders that can be treated in accordance with the present invention include, but are not limited to, panic disorder; agoraphobia; a specific phobia; social phobia; obsessive-compulsive disorder; post-traumatic stress disorder; acute stress disorder; and generalized anxiety disorder. This invention additionally provides a method of treating a drug addiction, for example an addiction to alcohol, amphetamine, cocaine, or opiate, in a mammal, including a human, said method comprising administering to said mammal an amount of a compound of formula I effective in the treatment of drug addiction. This invention also provides a method of treating a drug addiction, for example an addiction to alcohol, amphetamine, cocaine, or opiate, in a mammal, including a human, said method comprising administering to said mammal an amount of a compound of formula I effective in the inhibition of PDE10. A "drug addiction", as used in this specification, means an abnormal desire for a drug and is generally characterized by motivational disturbances such as a compulsion to take the desired drug and episodes of intense drug craving. This invention further provides a method of treating a disorder which comprises as a symptom a deficiency in attention and / or cognition in a mammal, including a human, said method comprising administering to said mammal an amount of a compound of formula I effective in the treatment of said disorder. This invention also provides a method of treating a disorder or condition comprising as a symptom a deficit in attention and / or cognition in a mammal, including a human, said method comprising administering to said mammal an amount of a compound of Formula I effective in inhibiting PDE10. This invention also provides a method of treating a disorder or condition comprising as a symptom a deficiency in attention and / or cognition in a mammal, including a human, said method comprising administering to said mammal an amount of a compound of Formula I effective in the treatment of said disorder or condition.

The phrase "deficiency in attention and / or cognition" as used in this specification in "disorder comprising as a symptom a deficiency in attention and / or cognition" refers to subnormal functioning in one or more cognitive aspects such as memory , intellect, or learning and logical capacity, in a particular individual in relation to other individuals within the same population of general age. "Deficiency in attention and / or cognition" also refers to a reduction in any functioning of the particular individual in one or more cognitive aspects, for example as in the cognitive deterioration related to age. Examples of disorders comprising as a symptom a deficit in attention and / or cognition that can be treated in accordance with the present invention are dementia, eg, Alzheimer's disease, multi-infarct dementia, alcoholic dementia or other drug-related dementia, dementia. associated with intracranial tumors or brain trauma, dementia associated with Huntington's disease or Parkinson's disease, or dementia related to AIDS; delirium; amnestic disorder; post-traumatic stress disorder; Mental retardation; a learning disorder, for example, reading disorder, math disorder, or a written expression disorder; hyperactivity disorder with attention deficit; and cognitive impairment related to age. This invention also provides a method of treating a mood disorder or mood episode in a mammal, including a human being, comprising administration to said mammal. mammal of an amount of a compound of formula I effective in the treatment of said disorder or episode. This invention also provides a method of treating a mood disorder or mood episode in a mammal, including a human, said method comprising administering to said mammal an amount of a compound of formula I effective in inhibiting PDE10. . Examples of mood disorders and mood episodes that can be treated in accordance with the present invention include, but are not limited to, major depressive episode, mild, moderate or severe, an episode of manic or mixed mood, an episode of hypomanic mood; a depressive episode with atypical features; a depressive episode with melancholic characteristics; a depressive episode with catatonic characteristics; an episode of mood with beginning after childbirth; depression after stroke; major depressive disorder; dysthymic disorder; minor depressive disorder; premenstrual dysphoric disorder; post-psychotic depressive disorder of schizophrenia; a major depressive disorder superimposed on a psychotic disorder such as a hallucinatory disorder or schizophrenia; a bipolar disorder, for example bipolar I disorder, bipolar II disorder, and cyclothymic disorder. This invention also provides a method of treating a neurodegenerative disorder or condition in a mammal, including a human, said method comprising administration to said mammal of an amount of a compound of formula I effective in the treatment of such disorder or condition. This invention also provides a method of treating a neurodegenerative disorder or condition in a mammal, including a human, said method comprising administering to said mammal an amount of a compound of formula I effective in inhibiting PDE10. As used in this specification, and unless otherwise indicated, a "neurodegenerative disorder or condition" refers to a disorder or condition that is caused by the dysfunction and / or death of neurons in the central nervous system. The treatment of these disorders and conditions can be facilitated by the administration of an agent that prevents the dysfunction or death of neurons at risk in these disorders or conditions and / or enhances the function of damaged or healthy neurons in a way that compensates for the loss of function caused by the dysfunction or death of neurons at risk. The term "neurotrophic agent" as used in this specification refers to a substance or agent that has some or all of these properties. Examples of neurodegenerative disorders and conditions that can be treated in accordance with the present invention include, but are not limited to, Parkinson's disease, Huntington's disease; dementia, for example Alzheimer's disease, multi-infarct dementia, AIDS-related dementia, and frontotemporal dementia; neurodegeneration associated with brain trauma; neurodegeneration associated with stroke, neurodegeneration associated with cerebral infarction; neurodegeneration induced by hypoglycaemia; neurodegeneration associated with epileptic seizure; neurodegeneration associated with neurotoxin poisoning; and multisystemic atrophy. In one embodiment of the present invention, the neurodegenerative disorder or condition comprises neurodegeneration of the spiny neurons of the mid-striatum in a mammal, including a human. In a further embodiment of the present invention, the neurodegenerative disorder or condition is Huntington's disease. In another embodiment, this invention provides a pharmaceutical composition for treating psychotic disorders, hallucinatory disorders and drug-induced psychosis; anxiety disorders, movement disorders, mood disorders, neurodegenerative disorders and drug addiction, comprising an amount of a compound of formula I effective in the treatment of said disorder or condition. In another embodiment, this invention provides a method of treating a disorder selected from psychotic disorders, hallucinatory disorders and drug induced psychosis.; anxiety disorders, movement disorders, mood disorders, and neurodegenerative disorders, said method comprising administering an amount of a compound of claim 1 effective in the treatment of said disorder.

In another embodiment, this invention provides a method of treating the above disorders, wherein the disorders are selected from the group consisting of: dementia, Alzheimer's disease, multi-infarct dementia, alcoholic dementia or other drug-related dementia, dementia associated with intracranial tumors or brain trauma, dementia associated with Huntington's disease or Parkinson's disease, or dementia related to AIDS; delirium; amnestic disorder; post-traumatic stress disorder; Mental retardation; a learning disorder, for example, reading disorder, math disorder, or a written expression disorder; Attention deficit / hyperactivity disorder; cognitive impairment related to age, major depressive episode of mild, moderate or severe type; an episode of manic or mixed mood; an episode of hypomanic mood; a depressive episode with atypical features; a depressive episode with melancholic characteristics; a depressive episode with catatonic characteristics; an episode of mood with beginning after childbirth; depression after stroke; major depressive disorder; dysthymic disorder; minor depressive disorder; premenstrual dysphoric disorder; post - psychotic depressive disorder of schizophrenia; a major depressive disorder superimposed on a psychotic disorder comprising a hallucinatory disorder or schizophrenia; a bipolar disorder comprising bipolar I disorder, bipolar II disorder, cyclothymic disorder, Parkinson's disease; Huntington's disease; dementia, Alzheimer's disease, multi-infarct dementia, dementia related to AIDS, dementia frontotemporal; neurodegeneration associated with cerebral trauma; neurodegeneration associated with apoplexy; neurodegeneration associated with cerebral infarction; neurodegeneration induced by hypoglycaemia; neurodegeneration associated with epileptic seizures; neurodegeneration associated with neurotoxin poisoning; multisystemic, paranoid, disorganized, catatonic, undifferentiated or residual atrophy; schizophreniform disorder; schizoaffective disorder of the hallucinatory or depressive type; hallucinatory disorder; psychotic disorder induced by substances, psychosis induced by alcohol, amphetamine, cannabis, cocaine, hallucinogens, inhalants, opioids, or phencyclidine; Paranoid type personality disorder; and personality disorder of the schizoid type. The term "aryl", as used herein, unless otherwise indicated, includes an organic radical derived from a monovalent aromatic hydrocarbon and includes, but is not limited to, phenyl, naphthyl and indenyl. The term "alkyl", as used herein, unless otherwise indicated, includes saturated monovalent hydrocarbon radicals having straight or branched moieties. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl and f-butyl. The term "alkenyl", as used herein, unless otherwise indicated, includes alkyl moieties having at least one carbon-carbon double bond in which alkyl is as defined above. Examples of alkenyl groups include, but are not limited to a, ethenyl and propenyl. The term "alkynyl", as used herein, unless otherwise indicated, includes alkyl moieties having at least one carbon-carbon triple bond in which alkyl is as defined above. Examples of alkynyl groups include, but are not limited to, ethynyl and 2-propynyl. The term "cycloalkyl", as used herein, unless otherwise indicated, includes alkyl groups comprising saturated non-aromatic cyclic alkyl moieties wherein alkyl is as defined above. Examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclopropyl ethyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl. Unless otherwise indicated, as used herein, the terms "heterocyclic" and "heterocycloalkyl" refer to non-aromatic cyclic groups containing one or more heteroatoms, preferably one to four heteroatoms, each selected from O, S and N. The "heterobicycloalkyl" groups are cyclic groups of two non-aromatic rings, wherein said rings share one or two atoms, and in which at least one of the rings contains a heteroatom (O, S, or N) The heterobicycloalkyl groups for purposes of the present invention, and unless otherwise indicated, include spiro groups and fused ring groups. The "heterotricycloalkyl" groups are non-aromatic three ring cyclic groups, wherein said rings are fused together or they form a spiro group (in other words, at least two of said rings share one or two atoms and the third ring shares one or two atoms with at least one of said two rings). The heterotricycloalkyl groups of the compounds of the present invention may include one or more O, S and / or N heteroatoms. In one embodiment, each ring in the heterobicycloalkyl or heterocycloalkyl contains up to four heteroatoms (i.e., from zero to four heteroatoms, with such that at least one ring contains at least one heteroatom). The heterocycloalkyl, heterobicycloalkyl and heterotriccycloalkyl groups of the present invention may also include ring systems substituted with one or more oxo moieties. Heterocyclic groups, which include the heterobicyclic and heterotricyclic groups, can comprise double or triple bonds, for example, heterocycloalkenyl, heterobicycloalkenyl, and heterotricycloalkenyl. Examples of non-aromatic heterocyclic groups are aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, azepinyl, piperazinyl, 1,2,3,6-tetrahydropyridinyl, oxiranyl, oxetanyl, tetrahydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, tetrahydrothiopyranyl, morpholino, thiomorphonyl, thioxanyl, pyrrolinyl, indolinyl. , 2H-pyranyl, 4H-pyranyl, dioxanyl, 1,3-dioxolanyl, pyrazolinyl, dihydropyranyl, dihydrothienyl, dihydrofuranyl, pyrazolidinyl, imidazolinyl, midazolidinyl, 3-azabicyclo [3.1.0] hexanyl, 3-azabicyclo [4.1.0] heptanil, quinolizinyl, quinuclidinyl, 1,4-dioxaespiro [4.5] decyl, 1,4-dioxaespiro [4.4] nonyl, 1,4-dioxaespiro [4.3] octyl, and 1,4-dioxaespiro [4.2] heptyl. "Heteroaryl", as used herein, refers to to aromatic groups containing one or more heteroatoms (O, S, or N), preferably between one and four heteroatoms. A multicyclic group containing one or more heteroatoms in which at least one ring of the group is aromatic is a "heteroaryl" group. The heteroaryl groups of this invention may also include ring systems substituted with one or more oxo moieties. Examples of pyridinyl heteroaryl, pyridazinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, quinolyl, isoquinolyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, indolyl, benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl , phthalazinyl, triazinyl, isoindolyl, purinyl, oxadiazolyl, thiadiazolyl, furazanyl, benzofurazanyl, benzothiophenyl, benzotriazolyl, benzothiazolyl, benzoxazolyl, quinazolinyl, quinoxalinyl, naphthyridinyl, dihydroquinolyl, tetrahydroquinolyl, dihydroisoquinolyl, tetrahydroisoquinolyl, benzofuryl, furopyridinyl, pyrolopyrimidinyl, and azaindolyl. "Halogen" and "halo", as used herein, include chlorine, bromine, fluorine and iodine. "Haloalkyl" as used herein, includes alkyl groups in which one or more of the hydrogen atoms are substituted by halogens. Examples of haloalkyl include, but are not limited to -CH2F, -CHCI2, -CF3 and -CH2CF3. Unless otherwise indicated, the term "one or more" substituents or "at least one" substituent as used herein, refers to one to the maximum number of possible substituents based on the number of available binding sites. "Neurotoxin poisoning" refers to poisoning caused by a neurotoxin. A neurotoxin is any chemical agent or substance that can cause neural death and thus neurological damage. An example of a neurotoxin is alcohol, which, when abused by a pregnant woman, can result in alcohol intoxication and neurological damage known as fetal alcohol syndrome in a newborn. Other examples of neurotoxins include, but are not limited to, kainic acid, domoic acid, and acromelic acid; certain pesticides, such as DDT; certain insecticides, such as organophosphates; volatile organic solvents such as hexacarbons (e.g., toluene); heavy metals (for example, lead, mercury, arsenic, and phosphorus); aluminum; certain chemical agents used as weapons, such as orange agent and nerve gas; and neurotoxic antineoplastic agents. As used herein, the term "selective PDE10 inhibitor" refers to a substance, for example, an organic molecule that effectively inhibits an enzyme of the PDE10 family to a greater degree than the families' enzymes. PDE 1 - 9 or the PDE11 family. In one embodiment, a selective inhibitor of PDE10 is a substance, for example an organic molecule, which has an Cl50 for inhibition of PDE10 that is less than or about half the Cl50 that the substance has for the inhibition of any other PDE enzyme. In other words, the substance inhibits the activity of PDE10 to the same degree concentration about one tenth or less of the concentration required for any other PDE enzyme. In general, a substance is considered to effectively inhibit the activity of PDE10 if it has an IC50 of less than or about 10 μ ?, preferably less than or about 0.1 μ. A "selective PDE10 inhibitor" can be identified, for example, by comparing the ability of a substance to inhibit the activity of PDE10 with its ability to inhibit PDE enzymes of the other PDE families. For example, a substance can be assayed for its ability to inhibit the activity of PDE10, as well as PDE1, PDE2, PDE3, PDE4, PDE5, PDE6, PDE7, PDE8, PDE9, PDE1, including subtypes. The term "treat", as in "a method for treating a disorder", refers to reversing, alleviating or inhibiting the progress of the disorder to which such a term applies, or one or more symptoms of the disorder. As used herein, this term also encompasses, depending on the condition of the patient, preventing the disorder, including preventing the onset of the disorder or any symptoms associated with it, as well as reducing the severity of the disorder or any of its symptoms. Before the beginning. "Treat", as used herein, also refers to preventing a recurrence of a disorder. For example, "treatment of schizophrenia, or schizop reniform or schizoaffective disorder" as used in this document it also encompasses treatment of one or more symptoms (positive, negative, and other associated characteristics) of said disorders, for example, treatment of delusions and / or hallucinations associated therewith. Other examples of symptoms of schizophrenia and schizophreniform and schizoaffective disorders include disorganized speech, affective discouragement, alogy, anhedonia, inappropriate affect, dysphoric mood (in the form of, for example, depression, anxiety or anger), and some indications of cognitive dysfunction. In another embodiment, the present invention relates to a process for preparing a compound of formula 1 which comprises reacting a compound of formula III wherein R-i, R2 and Rs have been previously defined; and L is a suitable leaving group; with a compound of formula II II Examples of leaving groups include, but are not limited to, chlorine, bromine, iodine, p-toluenesulfonate, alkyl (Ci-C &) sulfate, and alkane (Ci-C) sulfonate, particularly trifluoromethanesulfonate. In a preferred embodiment, the leaving group L is chloro. Suitable methods for producing the compounds of the present invention can be found in the compounds of U.S. Patent No. 4,370,328, GB 2,000, 136 and US series numbers 1 1/257, 179 and 1/178, 104 incorporated herein by reference in its entirety. The compound of the invention can be administered either alone or in combination with pharmaceutically acceptable carriers, in single dose or multiple doses. Suitable pharmaceutical carriers include diluents or solid inert fillers, sterile aqueous solutions and various organic solvents. Therefore the pharmaceutical compositions formed can then be easily administered in a variety of dosage forms such as tablets, powders, lozenges, liquid preparations, syrups, injectable solutions and the like. These pharmaceutical compositions may optionally contain additional ingredients such as flavors, binders, excipients and the like. Thus, the compound of the invention can be formulated for oral, buccal, intranasal, parenteral (e.g. intravenous, intramuscular or subcutaneous), transdermal (e.g., patch) or rectal administration, or in a form suitable for administration by inhalation or insufflation.

For oral administration, the pharmaceutical compositions may take the form of, for example, tablets or capsules prepared by conventional means with pharmaceutically acceptable excipients such as binding agents (e.g., pregelatinized maize starch, polyvinylpyrrolidone or hydroxypropylmethylcellulose); fillers (for example, lactose, microcrystalline cellulose or calcium phosphate); lubricants (for example, magnesium stearate, talc or silica); disintegrants (e.g., potato starch or sodium starch glycolate); or wetting agents (e.g., sodium lauryl sulfate). The tablets can be coated by methods well known in the art. Liquid preparations for oral administration may take the form of, for example, solutions, syrups or suspensions, or may be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid preparations can be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (for example, sorbitol syrup, methylcellulose or hydrogenated edible fats); emulsifying agents (for example, lecithin or gum arabic); non-aqueous vehicles (e.g., almond oil, oily esters or ethyl alcohol); and preservatives (for example, methyl or propyl p-hydroxybenzoates or sorbic acid). For buccal administration, the composition may take the form of tablets or lozenges formulated in conventional manner. The compounds of the invention can be formulated for parenteral administration by injection, including the use of conventional catheterization techniques or infusion. Formulations for injection may be presented in unit dosage form, for example, in ampules or multi-dose containers, with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending agents, stabilizers and / or dispersing agents. Alternatively, the active ingredient may be in powder form for reconstitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use. When a product solution is required, it can be prepared by dissolving the isolated inclusion complex in water (or other aqueous medium) in an amount sufficient to generate a solution of the resistance required for oral or parenteral administration to patients. The compounds can be formulated for fast dispersing pharmaceutical forms (fddf), which are designed to release the active ingredient in the oral cavity. These are often formulated using gelatin-based matrices that rapidly solubilize. These dosage forms are well known and can be used to distribute a wide range of drugs. The fastest dispersing pharmaceutical forms use gelatin as a vehicle or structuring agent. Typically, gelatin is used to provide sufficient strength to the pharmaceutical form to prevent breakage during package removal, but once placed in the mouth, the gelatin allows immediate dissolution of the pharmaceutical form. Alternatively, various starches are used for the same effect. The compounds of the invention can also be formulated in rectal compositions such as suppositories or retention enemas, for example, containing conventional suppository bases such as cocoa butter or other glycerides. For intranasal administration or administration by inhalation, the compounds of the invention are conveniently distributed in the form of a solution or suspension from a pump spray container that is pressed or pumped by the patient or with an aerosol spray presentation. from a pressurized container or a nebulizer, with the use of a suitable propellant, for example, dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol, the dosage unit can be determined by providing a valve to distribute a measured amount. The pressurized container or nebulizer may contain a solution or suspension of the active compound. Capsules and cartridges (made, for example, of gelatin) for use in an inhaler or insufflator can be formulated containing a powder mixture of a compound of the invention and a suitable powder base such as lactose or starch. Aerosol formulations for the treatment of the aforementioned conditions (e.g., migraine) in the being The human adult medium is preferably arranged so that each measured dose or "burst" of aerosol contains about 20 mg to about 1000 mg of the compound of the invention. The overall daily dose with an aerosol will be in the range between about 100 mg and about 10 mg. The administration can be several times a day, for example, 2, 3, 4 or 8 times, giving for example, 1, 2 or 3 doses each time. A proposed daily dose of the compound of the invention, for oral, parenteral, rectal or buccal administration to the adult adult medium for the treatment of the aforementioned conditions, is between about 0.01 mg and about 2000 mg, preferably between about 0.1 mg and about 200 mg of the active ingredient of formula I per unit dose, which could be administered, for example, from 1 to 4 times a day. Assay procedures are available to select a substance for inhibition of the hydrolysis of cyclic nucleotides by PDE 10 and PDEs from other gene families. The concentration of cyclic nucleotide substrate used in the assay is 1/3 of the Km concentration, allowing comparisons of the Cl50 values through the different enzymes. The activity of the PDE is measured using a procedure based on scintillation proximity assay (SPA) as previously described (Fawcett et al., 2000). The effect of PDE inhibitors is determined by assaying a fixed amount of enzyme (PDE 1-11) in the presence of varying concentrations of substance and under substrate, so that Cl50 approaches the K i (cGMP or cAMP in a 3: 1 ratio of unmarked to marked 3 [H] at a concentration of 1/3 Km). The final assay volume is brought up to 00 μ? with assay buffer [20 mM Tris-HCl pH 7.4, 5 mM MgCl 2, 1 mg / ml bovine serum albumin]. Reactions are initiated with enzyme, incubated for 30-60 minutes at 30 ° C providing <30% substrate exchange and finished with 50 μ? of yttrium silicate SPA beads (Amersham) (containing a 3 mM concentration of the respective unlabeled cyclic nucleotide for PDEs 9 and 11). The plates were hermetically sealed and shaken for 20 minutes, after which the beads were allowed to settle for 30 minutes in the dark and then counted in a TopCount plate reader (Packard, Meriden, CT). The radioactivity units can be converted into percent activity of an uninhibited control (100%), plotted against the inhibitor concentration, and the Cl50 values of the inhibitor can be obtained using the Microsoft Excel extension "Fit Curve" " The following examples illustrate the present invention. However, it is to be understood that the invention, fully described in this specification and set forth in the claims, is not intended to be limited by the details of the following examples.

EXAMPLES General procedure for the preparation of 4-aminophthalazine derivatives To a 0.2 M solution of 4-chloro-6,7-dimethoxyptalazine (prepared as described in US Pat. No. 4,370,328) in tetrahydrofuran is added an equal volume of saturated aqueous sodium bicarbonate. Amine component NHR2 is added to the stirred mixture (amines prepared as in U.S. Publication Nos. 2006-0183763A1 (USSN 11/257179) and 2006-0019975A1 (USSN 11/178104) are incorporated herein by reference in its entirety) and the resulting mixture is heated to a gentle reflux for 1-24 hours. The mixture is cooled to room temperature and partitioned between water and ethyl acetate. The organic part is washed with brine, dried over magnesium sulfate, filtered and concentrated to give the crude product without a base. The material is purified either by chromatography on silica gel, or by the formation of a hydrochloride salt and recrystallization. The following prophetic examples can be made by the General Procedure described above. - (4-methoxyphenyl) -1- (6,7-dimethoxyptalazin-1-yl) piperidin-3-ol; 4,5,6, 7-tetrahydro-5- (6,7-dimethoxyptalazin-1-yl) -N-phenylthiazolo [5,4-c] pyridin-2-amine; 1- (4 - ((pyridin-4-yl) methoxy) piperidin-1-yl) -6,7-dimethoxy-phthalazine 1 - (6,7-dimethoxyptalazin-1-yl) - 4-phenylpiperidin-4-ol, 4-benzyl-1- (6,7-dimethoxyptalazin-1-yl) piperidin-4-ol; [1- (6,7-d¡methoxy-phthalazin-1-yl) piperidin-4-yl] (phenyl) methanone; 1- [4- (1 H-123-benzothiazol-1-yl) piperidn-1-yl] -6,7-dimethoxyptalazine; 6,7-dimethoxy-1- [4- (3-methylphenoxy) piperidin-1-yl] phthalazine; 6,7-dimethoxy-1- [4- (2-methylphenoxy) piperidin-1-yl] phthalazine; 6,7-dimethoxy-1- (4-pyridin-2-ylpiperidin-1-yl) phthalazine; 1- (4-benzylpiperidin-1-yl) -6,7-dimethoxyptalazine; 1- [4- (benzyloxy) piperidin-1-yl] -6,7-dimethoxyptalazine; 1- (6,7-dimethoxyptalazin-1-yl) -4-phenylpiperidine-4-carbonitrile 1- (6,7-dimethoxyptalazin-1-yl) -4- (3-fluorophenyl) piperidin-4-ol 6.7 -dimethoxy-1- (4-phenoxypiperidin-1-yl) phthalazine; 6,7-dimethoxy-1- [4- (2-methoxyphenoxy) piperidin-1-yl] phthalazine; 6,7-dimethoxy-1- (3-phenylpiperidin-1-yl) phthalazine; 6,7-dimethoxy-1- (3-phenoxypiperidin-1-yl) phthalazine; 6,7-dimethoxy-1- [3- (2-methoxyphenyl) piperidin-1-yl] phthalazine; 1- [4- (3-ethyl-1, 2,4-oxadiazol-5-yl) piperidin-1-yl] -6,7-dimethoxyptalazine; 1- [3- (3-ethyl-1, 2,4-oxadiazol-5-yl) piperidin-1-yl] -6,7- dimethoxyphthalazine; 2-. { [1- (6,7-dimethoxyptalazin-1-yl) piperidin-4-yl] oxy} benzonitrile 1- [4- (5-ethyl-1, 2,4-oxadiazol-3-yl) piperidin-1-yl] -6,7-dimethoxyptalazine; 6,7-dimethoxy-1- [4- (3-methoxyphenoxy) piperidin-1-yl] phthalazine; 6,7-dimethoxy-1- [4- (4-methoxyphenoxy) piperidin-1-yl] phthalazine; 1- [4- (2-fluorophenyl) piperidin-1-yl] -6,7-dimethoxyptalazine; 6,7-dimethoxy-1- [3- (3-methyl-1, 2,4-oxadiazol-5-yl) pipendin-1-yl] phthalazine; 6,7-dimethoxy-1 - [3- (4-methylphenoxy) piperidin-1-yl] phthalazine; 1- [4- (3,5-dimethyl-4H-1, 2,4-triazol-4-yl) piperidin-1-yl] -6,7-dimethoxyptalazine; 6,7-dimethoxy-1- [3- (3-methyl-phenoxy) piperidin-1-yl] phthalazine; 6,7-dimethoxy-1- [3- (2-methoxyphenoxy) piperidin-1-yl] phthalazine; 6,7-dimethoxy-1- [3- (4-methoxyphenoxy) piperidin-1-yl] phthalazine; 6,7-dimethoxy-1- [4- (3-methyl-1, 2,4-oxadiazol-5-yl) piperidin-1-yl] phthalazine; 6,7-dimethoxy-1- [3- (4-methyl-4H-1, 2,4-triazol-3-yl) piperidin-1-yl] phthalazine; 1- (6,7-dimethoxyptalazin-1 -yl) -4- (4-fluorophenyl) piperidin-4-ol; 6,7-dimethoxy-1- [3- (3-methoxyphenyl) piperidin-1-yl] phthalazine; 1- (6,7-dimethoxyptalazin-1-yl) -3- (24-dimethylphenyl) piperidin-3-ol; 1- (6,7-dimethoxyptalazin-1-yl) -3- (2-ethylphenyl) piperidin-3-ol; 1- [1- (6,7-dimethoxyptalazin-1-yl) -4-phenylpiperidin-4-yl] ethanone; 1- [4- (13-benzoxazol-2-yl) piperidin-1-yl] -6,7-d¡methoxyptalazine 1- [3- (benzylloxy) piperidin-1-yl ] -6,7-dimethoxyptalazine; 1- [3- (13-benzoxazol-2-yl) piperidin-1-yl] -6,7-dii-Tethoxyptalazine; [1- (67-dimethoxyptalazin-1-yl) pperiod-3-yl] (pyridin-3-yl) methanone; [1- (67-dimethoxyphthalazin-1-yl) piperidin-3-yl] (1-methyl-1 H -amidazol-2-yl) methanone; [1- (6,7-D-methoxyptalazin-1-yl) p -peridin-4-yl] (phenol) methanol; [1- (6,7-dimethoxyptalazin-1-yl) piperidin-4-yl] (pyridin-2-yl) methanol; [1- (6,7-d¡methoxy-phthalazin-1-yl) piperidin-4-yl] (pyridin-3-yl) methanol; [1- (6,7-dimethoxyptalazin-1-yl) piperidin-4-yl] (1-methyl-1 H-imidazol-2-yl) methanol; e ^ -dimethoxy-l-tS-IS-methyl-l ^^ -oxadiazol-S-i piperidin-l-yl-phthalazine; 1 '- (6,7-dimethoxyptalazin-1-yl) -34-dihydro-2H-spiro [isoquinoline-14'-piperidine] 3- [1- (6,7-dimethoxyptalazin-1-yl) p Peridin-4-yl] phenol; 1- [3- (3-tert-butyl-1, 2,4-oxadistol-5-yl) pperidin-1-yl] -6,7-dimethoxyphthalazine; 1- [3- (4-chlorophenyl) piperidin-1-yl] -6,7-d-methoxyphthalazine; 6,7-dimethoxy-1- (4-pyridin-4-ylpperiod-1-yl) phthalazine; 1-. { 3 - [(2-fluorophenoxy) methyl] piperidn-1-yl} -6,7-dimethoxyptalazine [1- (6,7-dimethoxyptalazin-1-yl) piperidin-3-yl] (phenol) methanone; [1- (67-dimethoxyptalazin-1-yl) piperidin-3-yl] (pyridin-2-yl) methanone; 6,7-dimethoxy-1- [3- (5-methyl-1, 3,4-oxadiazol-2-yl) piperidin-1-yl] phthalazine; 6,7-dimethoxy-1- [4- (1 H -pyrazol-5-yl) pipendin-1-yl] phthalazine; [4-benzyl-1- (6,7-dimethoxyptalazin-1-yl) piperidin-4-yl] methanol; 67-dimethoxy-1- [4- (2-methylphenyl) pipendin-1-yl] phthalazine; 1- (6,7-dimethoxyptalazin-1-yl) -4- (4-methylphenyl) p'iperidin-4-ol; 6,7-dimethoxy-1- [3- (phenoxymethyl) piperidin-1-yl] phthalazine; 6,7-dimethoxy-1- (3. {[[(2-methylpyridin-3-yl) oxy] methyl.}. Piperidin-1-yl) phthalazine; 6 J-dimethoxy-1- (3. {[[(6-methylpyridin-3-yl) oxy] methyl] piperidin-1-yl) phthalazine; 3-. { [1- (6,7-dimethoxyptalazin-1-yl) piperidin-3-yl] methoxy} pyridin-2-amine 1- (6J-dimethoxyptalazin-1-yl) -3 - [(2-methyl-1H-imidazol-1-yl) methyl] piperidin-3-ol; 6,7-dimethoxy-1-. { 4- [5- (methoxymethyl) -1,4,4-oxadiazol-2-yl] piperidin-1-yl} phthalazine; 1- [4- (5-isobutyl-1, 3,4-oxadiazol-2-yl) piperidin-1-yl] -6,7-dimethoxyptalazine; 1- [3- (5-cyclopropyl-1, 3,4-oxadiazol-2-yl) piperidin-1-yl] -6,7-dimethoxyptalazine; 6,7-dimethoxy-1-. { 3- [5- (methoxymethyl) -1,4,4-oxadiazol-2-yl] piperidin-1- iljftalazine; 1-. { 5- [1- (6,7-dimethoxyptalazin-1-yl) piperidin-3-yl] -1,4,4-oxadiazol-2-yl} -N, N-dimethylmethanamine 6,7-dimethoxy-1-. { 4 - [(6-methylpyridazin-3-yl) methyl] piperidin-1-y! Jftalazine; 6 J-dimethoxy-1- [4- (pyrimidin-2-ylmethyl) piperidin-1-yl] phthalazine; 1- (6,7-dimethoxyptalazin-1-yl) -3- (1 H -pyrazol-1-ylmethyl) piperidin-3-ol; 67-dimethoxy-1- [4- (2-methylpyrimidin-4-yl) piperidin-1-yl] phthalazine; 6,7-dimethoxy-1- [3- (pindin-2-ylmethyl) piperidin-1-yl] phthalazine; 6 J-dimethoxy-1- [3- (pinmidin-2-ylmethyl) piperidin-1-yl] phthalazine; (3- {[[1- (6,7-dimethoxiftalazin-1-yl) piperidin-3-yl] methyl} phenyl) methanol; 6,7-dimethoxy-1-. { 3- [2- (methoxymethyl) pinmidin-4-yl] piperidin-1-yl-phthalazine; 6,7-dimethoxy-1- (3-pyrimidin-4-ylpiperidin-1-yl) phthalazine; 4- [1- (6,7-dimethoxyptalazin-1-yl) piperidin-4-yl] -N-ethyl-pyrimidin-2-amine 6,7-dimethoxy-1- (4-pyrimidin-4-ylpiperidin-1-yl) ) phthalazine; 1- (6,7-dimethoxyptalazin-1-yl) -4 - [(2-methyl-1 H-imidazol-1-yl) methyl] piperidin-4-ol; 6,7-dimethoxy-1- (4- [1, 2,4] triazolo [15-a] pyrimidin-7-ylpiperidin-1-yl) phthalazine; 1- [4- (2-cyclopropylpyrimidin-4-yl) piperidin-1-yl] -6,7- dimethoxyphthalazine; 1- [4- (5-cyclopropyl-1, 3,4-oxadiazol-2-yl) piperidin-1-yl] -6,7-dimethoxyptalazine; 6,7-dimethoxy-1- [4- (pyrazin-2-ylmethyl) piperidin-1-yl] phthalazine; 3- [1- (6J-dimethoxyptalazin-1-yl) piperidin-4-yl] benzamide 4- [1- (6,7-dimethoxyptalazin-1-yl) piperidin-4-yl] benzamide 6,7-dimethoxy- 1- (4-pyrimidin-2-ylpiperidin-1-yl) phthalazine; 1- [3- (3-chlorobenzyl) piperidin-1-yl] -6,7-dimethoxyptalazine; 6,7-dimethoxy-1- [3- (pyrimidin-5-ylmethyl) pipendin-1-yl] phthalazine; 4- [1- (6,7-dimethoxyptalazin-1-yl) piperidin-4-yl] -N, N-dimethyl-pyrimidin-2-amine 6,7-dimethoxy-1- [4- (pyrimidin-5-ylmethyl) pipendin-1-yl] talazine; 1- [3- (1 H-benzimidazol-2-yl) piperidin-1-yl] -6,7-dimethoxyptalazine; 1- [4- (4-fluorobenzyl) piperidin-1-yl] -6,7-dimethoxyptalazine; 6,7-dimethoxy-1- [3- (3-methylphenyl) piperidin-1-yl] phthalazine; 1 - [4- (2-fluorobenzyl) piperidin-1-yl] -6 J-dimethoxyptalazine; 6-dimethoxy-1-. { 3 - [(2-methyl-1 H-imidazol-1-yl) methyl] piperidin-1-yl} phthalazine; 6,7-dimethoxy-1- [4- (1 H -pyrazol-1-ylmethyl) piperidin-1-yl] phthalazine; 1- [4- (3-cyclopropyl-1, 2,4-oxadiazol-5-yl) piperidin-1-yl] -6,7-dimethoxyptalazine; 1- [3- (5-cyclopropyl-4H-1, 2,4-triazol-3-yl) piperidin-1-yl] -6,7-dimethoxyptalazine; 1- (67-dimethoxyptalazin-1-yl) -4- (2-fluoro-5-methylphenyl) piperidin-4-ol; 1- [4- (2-fluorophenoxy) piperidin-1-yl] -6,7-dimethoxyptalazine-1. { 3 - [(4-fluorophenoxy) methyl] piperidin-1-yl} -6,7-dimethoxyptalazine; 6,7-dimethoxy-1- [4- (pyridin-2-ylmethoxy) piperidin-1-yl] phthalazine; 6,7-dimethoxy-1-. { 4- [5- (methoxymethyl) -1, 2,4-oxadiazol-3-yl] p¡per¡din-1- I} phthalazine; 6,7-dimethoxy-1- [4- (3-methoxyphenyl) piperidin-1-yl] phthalazine; 1- [4- (3,5-difluorophenyl) piperidin-1-yl] -6,7-dimethoxyptalazine; 1 - [4- (3-fluorophenoxy) piperidin-1-yl] -6,7-dimethoxyptalazine; 1- [4- (4-fluorophenoxy) piperidin-1-yl] -6,7-dimethoxyptalazine; 4- [1- (6,7-dimethoxyptalazin-1-yl) piperidin-4-yl] benzonitrile 1 '- (6,7-dimethoxyptalazin-1-yl) spiro [chromene-2,4'-piperidine] 1- [3- (1 H-imidazol-2-yl) piperidin-1-yl] -6,7-dimethoxyptalazine; 1 '- (6,7-dimethoxyptalazin-1-yl) -34-dihydrospiro [isocromen-1,4'-piperidine] N- [1- (6,7-dimethoxyptalazin-1-yl) piperidin-4-yl] pyrimidin-2-amine N- [1- (6,7-dimethoxyptalazin-1-yl) piperidin-4-yl] pyridin-2-amine N-benzyl-1- (6,7-dimethoxyptalazin-1-yl) - N-methylpipendin-4-amine 6-dimethoxy-1- [4- (4-methylbenzyl) piperidn-1-yl] phthalazine; 1- [4- (4-chlorophenyl) -4-methylpiperidin-1-yl] -6,7-dimethoxyptalazine; 1 '- (67-dimethoxyptalazin-1-yl) spiro [indole-34'-piperidin] -2 (1 H) -one; 4-phenyl-1- (5,6,7-trimethoxyptalazin-1-yl) piperidin-4-ol; 4-benzyl-1- (5,6,7-trimethoxyptalazin-1-yl) pipendin-4-ol; phenyl [1- (5,6,7-trimethoxyptalazin-1-yl) p -peridin-4-yl] methanone; 1- [4- (1 H-123-benzothiazol-1-yl) piperidin-1-yl] -5,6,7-trimethoxyphthalazine; 5,6,7-trimethoxy-1- [4- (3-methylphenoxy) piperidin-1-yl] phthalazine; 5,6,7-trimethoxy-1- [4- (2-methylphenoxy) pperidin-1-yl] phthalazine; 5,6,7-trimethoxy-1- (4-pyridin-2-ylpiperidin-1-yl) phthalazine; 1- (4-benzylpipendin-1-yl) -5,6,7-trimethoxyphthalazine; 1 - [4- (benzyloxy) pperidin-1-yl] -5,6,7-trimethoxyptalazine; 4-phenyl-1- (5,6,7-trimethoxyptalazin-1-yl) piperidine-4-carbonitrile 4- (3-fluorophenyl) -1- (5,6,7-trimethoxyptalazin-1-yl) piperidin-4-ol; 5,6,7-trimethoxy-1- (4-phenoxypiperidin-1-yl) phthalazine; 5,6,7-trimethoxy-1- [4- (2-methoxyphenoxy) piperidin-1-yl] phthalazine; 5,6,7-trimethoxy-1- (3-phenylpipendin-1-yl) phthalazine; 5,6,7-trimethoxy-1- (3-phenoxypiperidin-1-yl) phthalazine; 5,6,7-trimethoxy-1 - [3- (2-methoxyphenyl) piperidin-1-yl] phthalazine; 1- [4- (3-ethyl-1, 2,4-oxadiazol-5-yl) pipendin-1-yl] -5,6,7-trimethoxyptalazine; 1- [3- (3-ethyl-1, 2,4-oxadiazol-5-yl) piperidin-1-yl] -5,6,7-trimethoxyptalazine; 2- . { [1- (5,6,7-trimethoxyptalazin-1-yl) piperidin-4-yl] oxy} benzonitrile l - ^ - IS-ethyl-l ^^ -oxadiazol-S-i piperidin-l-ylj-S.ey-trimethoxyptalazine; ,6,7-trimethoxy-1- [4- (3-methoxyphenoxy) piperidin-1-yl] phthalazine; 5,6,7-trimethoxy-1- [4- (4-methoxy-phenoxy) piperdin-1-yl] phthalazine; 1 - [4- (2-fluorophenyl) piperidn-1-yl] -5,6,7-tr ~ methoxyphthalazine; 5,6,7-trimethoxy-1- [3- (3-methyl-1, 2,4-oxadiazol-5-yl) piperidn-1-yl] phthalazine; 5,6,7-trimethoxy-1- [3- (4-methyloxy) piperidin-1-yl] phthalazine; 1- [4- (3,5-dimethyl-4H-1, 2,4-triazol-4-yl) p -peridin-1-yl] -5,6,7-trimethoxyptalazine; 5,6,7-trimethoxy-1 - [3- (3-methylphenoxy) piperidin-1-yl-phthalazine; 5,6,7-trimethoxy-1 - [3- (2-methoxyphenoxy) piperidin-1-yl-phthalazine; 5 > 6,7-trimethoxy-1 - [3- (4-methoxyphenoxy) piperidin-1-ylphthalazine; 5,6,7-trimethoxy-1 - [4- (3-methyl-1, 2,4-oxadiazol-5-yl) piperidin-1-yl-phthalazine; 5,6,7-trimethoxy-1- [3- (4-methyl-4H-1, 2,4-triazol-3-yl) piperidin-1-yl-phthalazine; 4- (4-fluorophenyl) -1- (5,6,7-trimethoxyptalazin-1-yl) piperidin-4-ol; S ^ and -trimethoxy-l-tS-IS-methoxypheni piperidin-l-yl-phthalazine; 3- (24-dimethylphenyl) -1- (5,6,7-trimethoxyptalazin-1-yl) piperidin-3-ol; 3- (2-Ethylphenyl) -1- (5,6,7-trimethoxyptalazin-1-yl) piperdin-3-ol; 1- [4-phenyl-1- (5,6,7-trimethoxyptalazin-1-yl) piperidin-4-yl] ethanone; 1- [4- (13-benzoxazol-2-yl) piperidin-1-yl] -5,6,7-trimethoxyptalazine; 1 - [3- (benzyloxy) piperidin-1-yl-5,6 J-trimethoxyphthalazine; 1- [3- (13-benzoxazol-2-yl) piperidin-1-ylJ-5,6,7-trimethoxyptalazine; pyridin-3-yl [1- (5,6,7-trimethoxyptalazin-1-yl) piperidin-3-yl] methanone; (1-methyl-1 H-imidazol-2-yl) [1- (5,6,7-trimethoxyptalazin-1-yl) piperdin-3-yl] methanone; phenyl [1- (5,6,7-tnmethoxyptalazin-1-yl) piperidin-4-yl] methanol; pindin-2-yl [1- (5,6,7-trimethoxyptalazin-1-yl) piperidin-4-yl] methanol; pyridin-3-yl [1- (5,6,7-tnmethoxyptalazin-1-yl) pipendin-4-yl] methanol; (1-methy1-H-methyl-2-yl) [T- (5,6-J-trimethoxyptalazin-1-yl) piperidin-4-l] methanol; 5,6,7-trimethoxy-1- [3- (5-methyl-1, 2,4-oxadiazol-3-yl) pipendin-1-yl] phthalazine; 1 '- (5,6,7-trimethoxyptalazin-1-yl) -34-dihydro-2 H-spiro [isoquinoline-14'-piperidine]; 3- [1 - (5,6,7-trimethoxyptalazin-1-yl) piperidin-4-yl] phenol; 1- [3- (3-tert-butyl-1, 2,4-oxadiazol-5-yl) piperidin-1-yl] -5,6,7-trimethoxyptalazine; 1- [3- (4-chlorophenyl) piperidin-1-yl] -5,6,7-trimethoxyptalazine; 5,6,7-trimethoxy-1- (4-pindin-4-ylpipendin-1-yl) phthalazine; 1-. { 3 - [(2-fluorophenoxy) methyl] piperidn-1-yl} 5,6,7-trimethoxyphthalazine phenyl [1- (5,6,7-tnmethoxyptalazin-1-yl) pipendin-3-yl] methanone; pyridin-2-yl [1- (5,6,7-tnmethoxy talazin-1-yl) piperidin-3-yl] methanone; 5,6,7-trimethoxy-l - [3- (5-methyl-1, 3,4-oxadiazol-2-yl) piperidin-1-yl] phthalazine; ,6,7-trimethoxy-1- [4- (1 H -pyrazol-5-yl) piperidin-1-yl] phthalazine; [4-benzyl-1- (5,6,7-trimethoxyptalazin-1-yl) piperidin-4-yl] methanol; 5,6,7-trimethoxy-1- [4- (2-methylphenyl) piperidin-1-yl] phthalazine; 4- (4-methylphenyl) -1- (5,6,7-trimethoxyptalazin-1-yl) pipendin-4-ol; 5,6,7-trimethoxy-1- [3- (phenoxymethyl) piperidin-1-yl] phthalazine; 5,67-trimethoxy-1- (3. {[[(2-methylpyridin-3-yl) oxy] methyl.}. Piperidin-1-yl) phthalazine; 5,67-tnmethoxy-1- (3. {[[(6-methylpindin-3-yl) oxy] methyl.}. Piperidin-1-yl) phthalazine; 3-. { [1- (5,6,7-trimethoxyptalazin-1-yl) piperidin-3-H] methoxy} pyridin-2-amine; 3 - [(2-methyl-1 H-imidazol-1-yl) methyl] -1- (5,6,7-tnmethoxyptalazin-1-yl) piperidin-3-ol; 5,6,7-trimethoxy-1-. { 4- [5- (methoxymethyl) -1,4,4-oxadiazol-2-yl] pipendin 1-il} phthalazine; 1- [4- (5-isobutyl-1,4,4-oxadiazol-2-yl) piperidin-1-yl] -5,6,7-trimethoxyptalazine; 1- [3- (5-cyclopropyl-1, 3,4-oxadiazol-2-yl) piperidin-1-yl] -5,6,7-trimethoxyphthalazine; 5,67-trimethoxy-1-. { 3- [5- (methoxymethyl) -1,4,4-oxadiazol-2-yl] pipendin 1-?} phthalazine; N, N-dimethyl-1-. { 5- [1- (5,6,7-tnmethoxyptalazin-1-yl) piperidin-3-yl] -1,4,4-oxadiazol-2-yl} methanamine 5,6J-trimethoxy-1-. { 4 - [(6-methylpyridazin-3-yl) methyl] piperidin-1-yl} phthalazine; 5,67-trimethoxy-1- [4- (pyrimidin-2-ylmethyl) piperidin-1-yl] phthalazine; 3- (1 H-pyrazol-1-ylmethyl) -1 - (5,6,7-trimethoxyptalazin-1-yl) piperidin-3-ol; 5,67-tnmethoxy-1- [4- (2-methylpyrimidin-4-yl) piperidin-1-yl] phthalazine; 5,6,7-trimethoxy-1 - [3- (pyridin-2-ylmethyl) piperidin-1-yl] phthalazine; 5,67-trimethoxy-1- [3- (pyrimidin-2-ylmethyl) piperidin-1-yl] phthalazine; (3- { [1- (5,67-trimethoxyptalazin-1-yl) piperidin-3-yl] methyl.} Phenyl) methanol; 5,6-trimethoxy-1-. { 3- [2- (methoxymethyl) pinmidin-4-yl] piperidin-1-yl} phthalazine; 5,6,7-trimethoxy-1- (3-pyrimidin-4-ylpiperidin-1-yl) phthalazine; N-ethyl-4- [1- (5,6,7-trimethoxyptalazin-1-yl) piperidin-4-yl] pinmidin-2-amine 5,6l7-trimethoxy-1- (4-pyrimidin-4-ylpiperidin- 1-yl) phthalazine; 4- [(2-methyl-1 H-imidazol-1-yl) methyl] -1- (5,6,7-trimethoxyptalazin-1-yl) piperdin-4-ol, 5,6,7- trimethoxy-1 - (4- [1, 2,4] triazolo [15-a] pyrimidin-7-ylpiperidin-1-yl) phthalazine; 1- [4- (2-cyclopropNpyrimidin-4-yl) piperidin-1-yl] -5,6,7- trimethoxyptalazine; 1- [4- (5-cyclopropyl-1, 3,4-oxadiazol-2-yl) piperidin-1-yl] -5,6,7-trimethoxyptalazine; 5,67-trimethoxy-1- [4- (pyrazin-2-ylmethyl) piperidin-1-yl] phthalazine; 3- [1 - (5,6,7-trimethoxyptalazin-1-yl) piperidin-4-yl] benzamide; 4- [1- (5,6,7-trimethoxyptalazin-1-yl) piperidin-4-yl] benzamide; 5,6,7-trimethoxy-1- (4-pyrimidin-2-ylpipendin-1-yl) phthalazine; 1- [3- (3-chlorobenzyl) piperidin-1-yl] -5,6,7-tnmethoxyptalazine; 5,6J-trimethoxy-1- [3- (pyrimidin-5-ylmethyl) pipendin-1-yl] phthalazine; N, N-dimethyl-4- [1- (5,6,7-trimethoxyphthalazin-1-yl) pyrimidin-4-yl] pyrimidin-2-amine 5,6J-trimethoxy- 1- [4- (pyrimidin-5-ylmethyl) piperidin-1-yl] phthalazine; 1- [3- (1 H-benzimidazol-2-yl) piperidin-1-yl] -5,6,7-trimethoxyphthalazine; 1- [4- (4-fluorobenzyl) piperidin-1-yl] -5,6,7-trimethoxyptalazine; 5,6,7-trimethoxy-1- [3- (3-methylphenyl) piperidin-1-yl] phthalazine; 1- [4- (2-fluorobenzyl) piperidin-1-yl] -5,6,7-tnmethoxyptalazine; 5,6J-tnmetoxi-1-. { 3 - [(2-methyl-1 H-imidazol-1-yl) methyl] pipendin-1-yl-phthalazine; 5,67-trimethoxy-1- [4- (1 H -pyrazol-1-ylmethyl) piperidin-1-yl] phthalazine; 1- [4- (3-cyclopropii-1, 2,4-oxadiazol-5-yl) piperidin-1-yl] -5,6,7-trimethoxyptalazine; 1- [3- (5-cyclopropyl-4H-1, 2,4-triazol-3-yl) piperidin-1-yl] -5,6,7-trimethoxyptalazine; 4- (2-fluoro-5-methylphenyl) -1 - (5,6,7-trimethoxyptalazin-1-yl) piperidin-4-ol; 1- [4- (2-fluorophenoxy) piperidin-1-yl] -5,6,7-tnmethoxyptalazine; 1 -. { 3 - [(4-fluorophenoxy) methyl] piperidin-1-yl} -5,6,7-trimethoxyphthalazine; 5,6,7-trimethoxy-1- [4- (pyridin-2-ylmethoxy) pipendin-1-yl] phthalazine; 5,6,7-trimethoxy-1-. { 4- [5- (methoxymethyl) -1,4, 2,4-oxadiazol-3-yl] pipendin-1-yl} phthalazine; 5,6,7-trimethoxy-1 - [4- (3-methoxyphenyl) piperidin-1-yl] phthalazine; 1- [4- (3,5-difluorophenyl) piperidin-1-yl] -5,6,7-trimethoxyptalazine; 1 - [4- (3-fluorophenoxy) piperidin-1-yl] -5,6,7-trimethoxyptalazine; 1 - [4- (4-fluorophenoxy) piperidin-1-yl] -5,6,7-trimethoxyptalazine; 4- [1 - (5,6,7-trimethoxyptalazin-1-yl) piperidin-4-yl] benzonitrile l '-ISej-trimethoxyptalazin-li spirotromenne ^' -piperidine] 1 - [3- (1 H- imidazol-2-yl) pipendin-1-yl] -5,6,7-trimethoxyptalazine; 1 '- (5,6,7-tnmetoxiftalazin-1-yl) -34-dihydrospiro [isocromen-14'-piperidine] N- [1- (5,6 J-tnmetoxiftalazin-1-yl) pipendin-4-il ] pyrimidin-2-amine N- [1- (5,6,7-trimethoxyptalazin-1-yl) pipendin-4-yl] pyridin-2-amine N-benzyl-N-methyl-l-SiS-trimethoxyptalazin -li piperidin -amine 5,6 J -trimethoxy-1 - [4- (4-methylbenzyl) piperidin-1-yl] phthalazine; 1 - [4- (4-chlorophenyl) -4-methylpiperidin-1-yl] -5,6,7-trimethoxyptalazine; and 1 '- (5,6 > 7-tnmetoxiftalazin-1-yl) spiro [indole-34'-piperidin] -2 (1 H) - ona; and its pharmaceutical salts. The invention described and claimed in this specification is not limited in scope by the specific embodiments described in this specification, since these modalities are proposed as illustrations of various aspects of the invention. Any equivalent embodiments are intended to be within the scope of this invention. In fact, various modifications of the invention in addition to those shown and described in this specification will be apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims.

Claims (1)

1. NOVELTY OF THE INVENTION CLAIMS 1. - A compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein ring A is a 5- or 6-membered heterocyclic ring substituted by at least one R6 and at least one R7; wherein R1, R2 and R5 are each independently H, halogen, -CN, -COOH, -COOR3, -CONR3R4, -COR20, -NR3R4, -NHCOR20, -OH, aryl (C6-C10), heteroaryl (5-10) members, (C6) alkyl, (C1-C6) alkenyl (C2-C6) alkenyl, (C2-C6) alkynyl, (C2C6) alkoxy, (C2-6) alkenyloxy or cycloalkyl ( C3-C8) io, when R1, R2 and R5 are independently alkoxy (C Ce), alkenyloxy (C2-C6), alkyl (Ci-C6), alkenyl (C2-C6) or alkynyl (C2-C6), R1 and R2 or R1 and R5 may be optionally connected forming a ring of 5 to 8 members; wherein R3 and R4 are each independently H, (C6) alkyl heteroaryl (5-10 members) or aryl (C6-C1C)), said heteroaryl or aryl being optionally substituted with one or more alkyl groups (Ci-C6) or halo; in which each R6 is independently H, halogen, -COOR 3, -CONR 3 R 4, -COR 20, -NR 3 R 4, -OH, hydroxyalkyl (C C 6) -HNCOOR 3, -CN, - HNCONHR 4, alkyl (d-C 6), (C 1 -C 6) alkoxy, aryl ( C6-C10), -O-alkylene (C1-C6) -heteroaryl (5-8 membered), -O-alkylene (C6) -aryl (C6-C10), -alkylene (C6) -O-heteraoaryl (5-8 members), -alkylene (Ci-C6) -O-aryl (C6-C10) or wherein n is 0 or 1; W is carbon, oxygen or NR, where R is hydrogen or alkyl (C Ce), and when W is carbon, it may be optionally substituted with halogen, -CN, -COOH, -COOR3, -CONR3R4, -COR20, - NR3R4, -NHCOR20, -OH, aryl (C6-Ci0), heteroaryl (5-10 members), alkyl (C6), haloalkyl (Ci-Ce) alkenyl (C2-C6), alkynyl (C2-C6) alkyloxy (Ci-C6), alkenyloxy (C2-Ce) or cycloalkyl (C3-C8); and wherein said alkyl, aryl or heteroaryl of R6 may be optionally substituted with (CrC8), (C3-C8) cycloalkyl, (CrC8) alkoxy, halogen, -OH, and haloalkyl (CrCe); wherein R9 and R10 are independently hydrogen or (C8) alkyl; or R9 and R10 can optionally be combined to form a cyclic ring; wherein each R7 is independently R1 1, -R18-R1 1 or -OR1 1; wherein R 1 1 is hydrogen, phenyl, naphthyl, or a 5- to 6-membered heteroaryl ring, optionally fused to a benzo group or heteroaryl ring, containing one to four heteroatoms selected from oxygen, nitrogen and sulfur, with the proviso that said heteroaryl ring can not contain two adjacent oxygen atoms or two adjacent sulfur atoms, and in which each of the following phenyl, naphthyl, heteroaryl, or benzo fused heteroaryl rings can be optionally substituted with each other three substituents independently selected from alkyl (Ci-C8), cycloalkyl (C3-C8), alkoxy (d-Ce), halogen, -CN, -OH, aryl (C6-Ci0), heteroaryl of (5-10) members, haloalkyl (C C8), hydroxyalkyl (Ci-C8), alkoxy (Ci-C8) -alkyl (d-C8), hydroxycycloalkyl (C Ce), cycloalkoxy (C3-C8), alkoxy (C8) -cycloalkyl (C3-) C8), (C3-C8) -heterocycloalkyl, (C3-C8) -hydroxyheterocycloalkyl, and (Ci-C8) -heterocycloalkyl-alkoxy, in which each cycloalkyl or heterocycloalkyl residue can be independently substituted with one to three halogens, alkyl (Ci-Ce) ) or benzyl groups; or when R11 is phenyl, naphthyl, or heteroaryl ring, each ring may be optionally substituted with one to three substituents independently selected from (a) lactone formed from - (CH2) tOH with an ortho -COOH, wherein t is one, two or three; (b) -CONR14R15 or (C0-C6) alkylene- NR1 R15, wherein R14 and R15 are each independently selected from hydrogen, alkyl (CrC8) and benzyl, or R14 and R5 together with nitrogen at which are joined form a heteraoalkyl ring of (5-7) members which may contain from zero to three heteroatoms selected from nitrogen, sulfur and oxygen in addition to the nitrogen of the group -CONR 4R15, wherein when any of said heteroatoms is nitrogen it may be optionally substituted with (Ci-C8) alkyl or benzyl, with the proviso that said ring does not contain two adjacent oxygen atoms or two adjacent sulfur atoms; (c) - (CH2) vNCOR16R17, wherein v is zero, one, two or three and -COR16 and R17 taken together with the nitrogen to which they are attached can form a 4- to 6- membered lactam ring; or when R 11 is heteroaryl, it may optionally be fused to a ring A and optionally substituted with -NR 1 R 13; wherein R12, R13, R16 and R17 are each independently hydrogen, alkyl (C Ce), and aryl (C6-Ci0); wherein R18 is (C1-C3) alkylene or -N (Ri9) -; wherein said alkylene may be optionally substituted with alkyl (CrC8), cycloalkyl (C3-C8), alkoxy (C-i-C8), halogen, -OH, or haloalkyl (CrC8); R19 is hydrogen or alkyl (d-C6); and wherein each R20 is independently alkyl (CrC8), cycloalkyl (C3-C8) alkoxy (Ci-C8), haloalkyl (CrC8), hydroxyalkyl (C8), alkoxy (Ci-C8) -alkyl (Ci-C8) , hydroxycycloalkyl (C3-C8), cycloalkoxy (C3-C8), alkoxy (C8) - cycloalkyl (C3-C8), heterocycloalkyl (C3-C8), aryl (C6-Cio) or heteroaryl (5-10) members . 2 - The compound according to claim 1, further characterized in that ring A is piperidine or pyrrolidine. 3. The compound according to claim 2, further characterized in that R1 and R2 are each independently (C1-C4) alkoxy. 4. The compound according to claim 2, further characterized in that R7 is R11 and R1 is phenyl optionally substituted with alkoxy (CrC6), alkyl (C1-C5), -CN, -OH, phenyl or substituted alkoxy (CrC6) with 1 to 3 halogens. 5. The compound according to claim 2, further characterized in that R7 is -OR11 and R11 is naphthyl or naphthyl substituted with alkoxy (? -? -? ß). 6. The compound according to claim 2, further characterized in that R7 is -OR11 and R11 is 5- or 6-membered heteroaryl. 7. The compound according to claim 2, further characterized in that R6 is alkoxy (CrC6) or -OH. 8 - The compound according to claim 2, further characterized in that R6 is -NR3R4 and R3 and R4 are each independently alkyl (CrC3). 9. The compound according to claim 2, further characterized in that R1 and R2 are each independently alkoxy (Ci-C6), R7 is R11 and R1 is phenyl or substituted phenyl and R6 is alkoxy (CrC6) or - OH. 10. The compound according to claim 1, further characterized in that R6 and R7 can not both be hydrogen. 11. The compound according to claim 1, further characterized in that said compound is selected from the group consisting of: 5- (4-methoxyphenyl) -1- (6,7-dimethoxyptalazin-1-yl) piperidin-3- ol; 4,5,6,7-tetrahydro-5- (6,7-dimethoxy-phthalazin-1-yl) -N-phenylthiazolo [5,4-c] pyridin-2-amine; 1- (4 - ((pyridin-4-yl) methoxy) piperidin-1-yl) -6,7-dimethoxyptalazine 1- (6,7-dimethoxyptalazin-1-yl) -4-phenylpiperidin-4-ol; 4-benzyl-1- (6,7-dimethoxyptalazin-1- L) p¡per¡din-4-ol; [1- (6,7-dimethoxiftalazin-1-yl) piperidin-4-yl] (phenyl) methanone; 1- [4- (1 H-123-benzotriazol-1-yl) piperdin-1-yl] -6,7-dimethoxyptalazine; 6,7-dimethoxy-1- [4- (3-methylphenoxy) piperidin-1-yl] phthalazine; 6,7-dimethoxy-1- [4- (2-methylphenoxy) piperidn-1-yl] phthalazine; 6,7-dimethoxy-1- (4-pyridin-2-ylpiperidin-1-yl) phthalazine; 1- (4-benzylpiperidin-1-yl) -6,7-dimethoxyptalazine; 1- [4- (benzyloxy) piperidin-1-yl] -6,7-dimethoxyptalazine; 1- (6,7-dimethoxyptalazin-1-yl) -4-phenylpiperidine-4-carbonitrile 1- (6,7-dimethoxy-phthalazin-1-yl) -4- (3-fluorophenyl) piperidine- 4-ol 6,7-dimethoxy-1- (4-phenoxypiperid-1-yl) phthalazine; 6,7-dimethoxy-1- [4- (2-methoxyphenoxy) piperidin-1-yl] phthalazine-6,7-dimethoxy-1- (3-phenylpiperidin-yl) phthalazine; 6,7-dimethoxy-1- (3-phenoxypiperidyl-1-yl) phthalazine-6,7-d, methoxy-1- [3- (2-methoxyphenyl) piper D1n-1-1] phthalazine; 1- [4- (3-ethyl-1, 2,4-oxadiazol-5-yl) pipendin-1-yl] -6,7-d-methoxyphthalazine; 1- [3- (3-ethyl-1, 2,4-oxadiazol-5-yl) piperdin-1-yl] -6,7-d-methoxy-phthalazine-2. { [1- (6,7-dimethoxyptalazin-1-yl) piperidn-4-yl] oxy} benzonitrillo 1 - [4- (5-ethyl-1, 2,4-oxadiazol-3-yl) piperdin-1-yl] -6,7-dimethoxyphthalazine; 6,7-dimethoxy-1- [4- (3-methoxyphenoxy) piperidin-1-yl] phthalazine] 6,7-dimethoxy-1- [4- (4-methoxyphenoxy) piperidin-1-yl] phthalazine; 1- [4- (2-fluorophenyl) piperidin-1-yl] -6,7-dimethoxyptalazine; 6,7-dimethoxy-1- [3- (3-methyl-1, 2,4-oxadiazol-5-yl) piperidin-1-yl] phthalazine; 6,7-dimethoxy-1- [3- (4-methylphenoxy) piperidin-1-yl] phthalazine; 1- [4- (3,5-dimethyl-4H-1, 2,4-triazol-4-yl) p -peridin-1-yl] -6,7-dimethoxyptalazine; 6,7-dimethoxy-1- [3- (3-methylphenoxy) piperidin-1-yl] phthalazine; 6,7-dimethoxy-1- [3- (2-methoxyphenoxy) piperidin-1-yl] phthalazine; 6,7-dimethoxy-1- [3- (4-methoxyphenoxy) piperidin-1-yl] phthalazine; 6,7-dimethoxy-1- [4- (3-methyl-1, 2,4-oxadiazol-5-yl) piperidin-1-yl] phthalazine; 6,7-dimethoxy-1- [3- (4-methyl-4H-1, 2,4-triazole-3- il) piperidin-1-yl] phthalazine; 1- (6,7-dimethoxyptalazin-1-yl) -4- (4-fluorophenyl) piperidn-4-ol; 6,7-dimethoxy-1 - [3- (3-methoxyphenyl) piperidin-1-yl] phthalazine; 1- (6,7-dimethoxyptalazin-1-yl) -3- (24-dimethylphenyl) piperidin-3-ol; 1- (6,7-dimethoxyptalazin-1-yl) -3- (2-ethylphenyl) piperidin-3-ol; 1- [1- (6,7-dimethoxyptalazin-1-yl) -4-phenylpiperidin-4-yl] ethanone; 1- [4- (13-benzoxazol-2-yl) piperidin-1-yl] -6,7-dimethoxyptalazine; 1- [3- (benzyloxy) pipendin-1-yl] -6,7-dimethoxyptalazine; 1- [3- (13-benzoxazol-2-yl) piperidin-1-yl] -6,7-dimethoxyptalazine; [1- (6,7-dimethoxyptalazin-1-yl) piperidin-3-yl] (pyridin-3-yl) methanone; [1- (6,7-dimethoxyptalazin-1-yl) pipendin-3-yl] (1-methyl-1 H -amidazol-2-yl) methanone; [1 - (6,7-dimethoxyptalazin-1-yl) piperidin-4-yl] (phenyl) methanol; [1- (6,7-dimethoxyptalazin-1-yl) piperidin-4-yl] (pindin-2-yl) methanol; [1- (6,7-dimethoxyptalazin-1-yl) piperidin-4-yl] (pindin-3-yl) methanol; [1- (6,7-dimethoxyptalazin-1-yl) piperidin-4-yl] (1-methyl-1 H-imidazol-2-yl) methanol; 6J-dimethoxy-1- [3- (5-methyl- 1, 2,4-oxadiazol-3-yl) pipendin-1-yl] phthalazine; 1 '- (6,7-dimethoxyptalazin-1-yl) -34-dihydro-2H-esp'iro [isoquinoline-14'-piperidine] 3- [1- (6,7-dimethoxyptalazin-1-yl) piperidin- 4-yl] phenol; 1- [3- (3-tert-butyl-1, 2,4-oxadiazol-5-yl) piperidin-1-yl] -6,7-dimethoxyptalazine; 1- [3- (4-chlorophenyl) piperidin-1 -yl] -6,7-dimethoxyptalazine; 6,7-dimethoxy-1- (4-pyridin-4-ylpiperidin-1-yl) phthalazine; 1 -. { 3 - [(2-fluorophenoxy) methyl] piperidin-1-yl} -6,7-dimethoxyptalazine; [1- (6,7-dimethoxyptalazin-1-yl) piperidin-3-yl] (phenyl) methanone; [1- (6,7-dimethoxyptalazin-1-yl) piperidin-3-yl] (pyridin-2-yl) methanone; 6,7-dimethoxy-1 - [3- (5-methyl-1, 3,4-oxadiazol-2-yl) piperidin-1-yl] phthalazine; 6,7-dimethoxy-1- [4- (1 H -pyrazol-5-yl) piperidin-1-N] phthalazine; [4-benzyl-1- (6,7-dimethoxyptalazin-1-yl) piperidin-4-yl] methanol; 6,7-dimethoxy-1- [4- (2-methylphenyl) piperidin-1-yl] phthalazine; 1- (6,7-dimethoxyptalazin-1-yl) -4- (4-methylphenyl) piperidn-4-ol; 6,7-dimethoxy-1- [3- (phenoxymethyl) piperidin-1-yl] phthalazine; 67-dimethoxy-1- (3. {[[(2-methylpyridin-3-yl) oxy] methyl} piperidin-1-yl) phthalazine; 6,7-dimethoxy-1- (3. {[[(6-methylpyridin-3-yl) oxy] methyl.}. Piperidin-1-yl) phthalazine; 3-. { [1- (6,7-dimethoxyptalazin-1-yl) piperidin-3-yl] methoxy} pyridin-2-amine 1- (6,7-dimethoxyptalazin-1-yl) -3 - [(2-methyl-1 H-imidazol-1-yl) methyl] piperidin-3-ol; 6,7-dimethoxy-1-. { 4- [5- (methoxymethyl) -1,4,4-oxadiazol-2-yl] piperidin-1-yl} phthalazine; 1- [4- (5-isobutyl-1, 3,4-oxadiazol-2-yl) piperidin-1-yl] -6,7-dimethoxyptalazine; 1 - [3- (5-cyclopropyl-1, 3,4-oxadiazol-2-yl) piperidin-1-yl] -6,7-dimethoxyptalazine; 6,7-dimethoxy-1-. { 3- [5- (methoxymethyl) -1,4,4-oxadiazol-2-yl] piperidin-1-yl} phthalazine; 1-. { 5- [1- (6,7-dimethoxyptalazin-1-yl) piperidin-3-yl] -1,4,4-oxadiazol-2-yl} -N, N-dimethylmethanamine 6,7-dimethoxy-1-. { 4 - [(6-methylpyridazin-3-yl) methyl] piperidin-1-yl} phthalazine; 6,7-dimethoxy-1- [4-pyrimidin-2-ylmethyl) piperidin-1-yl] phthalazine; 1- (6,7-dimethoxyptalazin-1-yl) -3- (1 H -pyrazol-1-ylmethyl) piperidin-3-ol; 6,7-dimethoxy-1- [4- (2-methylpyrimidin-4-yl) pipendin-1-yl] phthalazine; 6,7-dimethoxy-1- [3- (pyridin-2-ylmethyl) pipe din-1 -yl] phthalazine; 6,7-dimethoxy-1 - [3- (pyrimidin-2-ylmethyl) piperidin-1-yl] phthalazine; (3- { [1- (6,7-Dimethoxyptalazin-1-yl) piperidin-3-yl] methyl} phenyl) methanol; 6,7-dimethoxy-1. { 3- [2- (methoxymethyl) pyrimidin-4-yl] piperidin-1-yl} phthalazine; 6,7-dimethoxy-1- (3-pyrimidin-4-ylpiperidin-1-yl) phthalazine; 4- [1- (6,7-dimethoxyptalazin-1-yl) piperidin-4-yl] -N-ethyl-pyrimidin-2-amine 6,7-dimethoxy-1 - (4-pyrimidin-4-ylpiperidin- 1 -yl) phthalazine; 1- (6,7-dimethoxyptalazin-1-yl) -4 - [(2-methyl-1 H-imidazol-1-yl) methyl] piperidin-4-ol; 6,7-dimethoxy-1- (4- [1,4] triazolo [15-a] pinmidin-7-ylpiperidin-1-yl) phthalazine; 1- [4- (2-cyclopropylpyrimidin-4-yl) piperidin-1-yl] -6,7-dimethoxyptalazine; 1- [4- (5-cyclopropyl-1, 3,4-oxadiazol-2-yl) pipendin-1-yl] -6,7- dimethoxyphthalazine; 6,7-dimethoxy-1 - [4- (pyrazin-2-ylmethyl) piperidin-1-yl] phthalazine; 3- [1- (6,7-dimethoxyptalazin-1-yl) piperidin-4-yl] benzamide 4- [1- (6,7-d¡methoxyptalazin-1-yl) piperidin-4-yl] benzamide 6 , 7-dimethoxy-1- (4-pyrimidin-2-ylpiperidin-1-yl) phthalazine; 1- [3- (3-chlorobenzyl) piperidin-1-yl] -6,7-dimethoxyptalazine; 6,7-dimethoxy-1 - [3- (pyrimidin-5-ylmethyl) piperidin-1-yl-phthalazine; 4- [1 - (6,7-dimethoxyptalazin-1-yl) piperidin-4-yl] -N, N-dimethylpyrimidin-2-amine 6,7-dimethoxy-1- [4- (pyrimidin-5-ylmethyl) piperidin-1-yl] phthalazine; 1- [3- (1 H-benzimidazol-2-yl) piperidin-1-yl] -6,7-dimethoxyptalazine; 1- [4- (4-fluorobenzyl) piperidin-1-yl] -6,7-dimethoxyptalazine; 6,7-dimethoxy-1- [3- (3-methylphenyl) piperidin-1-yl] phthalazine; 1- [4- (2-fluorobenzyl) piperidin-1-yl] -6,7-dimethoxyptalazine; 6,7-dimethoxy-1-. { 3 - [(2-methyl-1 H-imidazol-1-yl) methyl] piperidin-1-yl} phthalazine; 6,7-dimethoxy-1 - [4- (1 H-pyrazolyl-methylmethyl) piperidin-1-yl] phthalazine; 1- [4- (3-cyclopropyl-1, 2,4-oxadiazol-5-yl) piperidin-1-yl] -6,7-dimethoxyptalazine; 1- [3- (5-cyclopropyl-4H-1, 2,4-triazol-3-yl) piperidin-1-yl] -6,7-dimethoxyptalazine; 1- (6,7-dimethoxyptalazin-1-yl) -4- (2-fluoro-5-methylphenyl) piperidin-4-ol; 1- [4- (2-fluorophenoxy) piperidin-1-yl] -6,7-dimethoxyptalazine 1-. { 3 - [(4-fluorophenoxy) methyl] piperidin-1-yl} -6,7-dimethoxyptalazine; 6,7-dimethoxy-1- [4- (pyridin-2-ylmethoxy) piperidin-1-yl] phthalazine; 6,7-dimethoxy-1 -. { 4- [5- (methoxymethyl) -1,4,4-oxadiazol-3-yl] piperidin-1-yl} phthalazine; 6,7-dimethoxy-1- [4- (3-methoxyphenyl) piperidin-1-yl] phthalazine; 1- [4- (3,5-difluorophenyl) piperidin-1-yl] -6,7-dimethoxyptalazine; 1- [4- (3-fluorophenoxy) piperidin-1-yl] -6,7-dimethoxyptalazine; 1- [4- (4-fluorophenoxy) piperidin-1-yl] -6,7-dimethoxyptalazine; 4- [1- (6,7-dimethoxyptalazin-1-yl) piperidin-4-yl] benzonitin 1 '- (6,7-dimethoxy-phthalazin-1-yl) spiro [chromene-2,4'-piperidine] 1- [3- (1 H-imidazol-2-yl) piperidin-1-yl] -6,7-dimethoxyptalazine; 1 '- (6,7- dimethoxyptalazin-li -S ^ dihydrospirotisocromeno-l ^ '-pipendine] N- [1- (6,7-d¡methoxtaphthalazin-1-yl) piperdin-4-yl] pyrimidin-2 -amine N- [1- (6,7-dimethoxy-phthalazin-1-yl) p -peridin-4-yl] pyridin-2-amine N-benzyl-1- (6,7-dimethoxy) Phthalazin-1-yl) -N-methyl-piperidin-4-amine 6,7-dimethoxy-1 - [4- (4-methylbenzyl) piperidn-1-yl] phthalazine; 1- [4- (4-chlorophenyl) -4-methyl-piperidin-1-yl] -6,7-d-methoxyphthalazine; 1 '- (6,7-dimethoxyphthalazin-1-yl) spiro [ndole-34'-piperidn] -2 (1 H) -one 4-phenyl-1 - (5, 6,7-trimethoxyphthalazin-1-yl) piperidin-4-ol; 4-benzyl-1 - (5,6,7-trimethoxyphthalazin-1-yl) pyridin-4-ol; phenyl [1 - (5,6,7-trimethoxyptalazin-1-yl) pperidin-4-yl] methanone; 1- [4- (1 H-123-benzotriazol-1-yl) piperidn-1-yl] -5,6,7-tr, methoxyphthalazine; 5,6,7-trimethoxy-1- [4- (3-methylphenoxy) piperidin-1-yl] phthalazine; 5,6,7-trimethoxy-1 - [4- (2-methylphenoxy) piperdin-1-yl] phthalazine; 5,6,7-trimethoxy-1- (4-pyridn-2-ylp yperidn-1-yl) phthalazine; 1 - (4-benzylpiperidn-1-l) -5,6,7-tr ~ methoxyptalazine 1 - [4- (benzyloxy) piperidin-1-yl] -5,6,7-tnmethoxyptalazine; 4-phenyl-1 - (5,6,7-trimethoxyptalazin-1-yl) piperidine-4-carbonitrile 4- (3-fluorophenyl) -1 - (5,6,7-tnmethoxyptalazin-1-yl) piperidin-4 -ol; 5,6,7-trimethoxy-1- (4-phenoxypiperidin-1-yl) phthalazine; 5,6,7-trimethoxy-1- [4- (2-methoxyphenoxy) pyrimidin-1-yl] phthalazine; 5,6,7-tnmethoxy-1- (3-phenylpiperidin-1-yl) phthalazine; 5,6,7-trimethoxy-1- (3-phenoxy-p -peridin-1-yl) phthalazine; 5,6,7-trimethoxy-1 - [3- (2-methoxyphenyl) piperidin-1-yl] phthalazine; 1 - [4- (3-ethyl-1, 2,4-oxadiazol-5-yl) piperidin-1-yl] -5,6,7-tnmethoxyptalazine; 1- [3- (3-ethyl-1, 2,4-oxadiazol-5-yl) piperidin-1-yl] -5,6,7-tr ymethoxyphtalazine-2. { [1 - (5,6,7-trimethoxyptalazin-1-yl) piperidin-4-yl] oxy]} benzontrile 1- [4- (5-ethyl-1, 2,4-oxadiazol-3-yl) p, peridn-1-yl] -5,6,7-tr, methoxyphthalazine; 5,6,7-trimethoxy-1 - [4- (3-methoxyphenoxy) pyridin-1-yl] phthalazine; 5,6,7-trimethoxy-1 - [4- (4- methoxyphenoxy) p.per.d.n.n-1-yl] phthalazine; 1- [4- (2-fluorophenyl) p.peridin-1-yl] -5,6,7-trimethoxyptalazine; S.ej-trimethoxy-l-fS-IS-methyl-l ^^ -oxadiazol-S-i piperidin-l-yl] phthalazine; 5,6,7-trimethoxy-1- [3- (4-methylphenoxy) piperidin-1-yl] phthalazine; 1- [4- (3,5-Dimeti Hl ^^ - triazole ^ - 'i p'iperidin-1-yl-S-y-trimethoxyptalazine; 5,6,7-trimethoxy-1 - [3- (3- methylphenoxy) piperidn-1-l] phthalazine, 5,6,7-trimethoxy-1 - [3- (2-methoxyphenoxy) pperidin-1-yl] phthalazine; 7-trimethoxy-1 - [3- (4-methoxyphenoxy) pyrimidin-1-yl] phthalazine; 5,6,7-trimethoxy-1- [4- (3-methyl-1 , 2,4-oxadiazol-5-yl) p, pyridyl-1-yl] phthalazine; 5,6,7-trimethoxy-1- [3- (4-methyl-4H-1, 2 , 4-triazol-3-yl) piperidin-1-yl] phthalazine; 4- (4-fluorophenyl) -1 - (5,6,7-trimethoxyptalazin-1-yl) piperidin-4-ol; , 6,7-trimethoxy-1 - [3- (3-methoxyphenyl) piperidin-1-yl] phthalazine; 3- (24-dylmethylphenyl) -1- (5,6, 7-trimethoxyphthalazin-1-yl) pyrimidin-3-ol; 3- (2-ethenyl) -1 - (5,6,7-trimethoxyptalazin-1-yl) p Peridin-3-ol; 1- [4-phenyl] -1- (5,6,7-trimethoxy-phthalazin-1-yl) piperdin-4-yl] ethanone, 1- [4- (13 -benzoxazol-2-yl) piperidin-1-yl] -5,6,7-trimethoxyptalazine; 1- [3- (benzyloxy) pperiod-1-yl] -5,6, 7-Trimethoxy-phthalazine; 1 - [3- (13-benzoxazol-2-yl) piperidn-1-yl] -5,6,7-tr'methoxyphthalazine; pyridin-3-yl [1 - (5,6,7-tr ~ methoxy-phthalazin-1-yl) piperidin-3-yl] methanone; (1-methy1-H-imidazol-2-yl) [1 - (5,6,7-trimethoxyptalazin-1-yl) piperidin-3-yl] methanone; phenyl [1 - (5,6,7-trimethoxyptalazin-1-yl) piperidin-4-yl] methanol; pyridin-2-yl [1- (5,6,7-tr ~ methoxy-phthalazin-1-yl) p-perdin-4-yl] methanol; pyridin-3-yl [1 - (5,6,7-trimethoxy-phthalaz'in-1-yl) p -peridin-4-yl] methanol; (1-methylene-1 H-imidazol-2-yl) [1- (5,6,7-tr¡methoxyphthalazin-1-yl) p¡per¡d¡n-4-yl] methanol; 5,6,7-trimethoxy-1 - [3- (5-methyl-1, 2,4-oxadiazol-3-yl) piperidn-1-yl] phthalazine; 1 '- (S.ej-tnmetoxiftalazin-li ^ -dihidro ^ H-spiro-isoquinoline-^' -piperidine]; 3- [1- (5,6,7-trimethoxiftalazin-1-yl) piperidin-4-yl] phenol; 1- [3- (3-tert-butyl-1, 2,4- oxadiazol-5-yl) p'iperdin-1-yl] -5,6,7-trimethoxyphthalazine; 1 - [3- (4-chlorophenol) piperidin-1-yl] -5,6,7-trimethoxyphthalazine; 5,6,7-trimethoxy-1- (4-pyridin-4-ylpiperidin-1-yl) phthalazine; 1-. { 3 - [(2-fluorophenoxy) methy1] piperidin-1-yl} -5,6,7-trimethoxyptalazine phenyl [1 - (5,6,7-trimethoxyphthalazin-1-yl) piperidin-3-yl] methanone; pyridin-2-yl [1 - (5,6,7-trimethoxyphthalazin-1-yl) pyrimidin-3-yl] methanone; 5,6,7-tnmethoxy-1- [3- (5-methyl-1, 3,4-oxadiazol-2-yl) piperidin-1-yl] phthalazine; 5,6,7-trimethoxy-1- [4- (1 H -pyrazol-5-yl) pperiod-1-yl] phthalazine; [4-benzyl-1- (5,6,7-trimethoxy-phthalazin-1-yl) piperidin-4-yl] methanol; 5,6,7-trimethoxy-1- [4- (2-methylphenyl) piperidn-1-yl] phthalazine; 4- (4-methyphenyl) -1 - (5,6,7-trimethoxyphthalazin-1-l) piperidin-4-ol; 5,6,7-trimethoxy-1 - [3- (phenoxymethyl) piperidin-1-yl] phthalazine; 5,6,7-Tristamethoxy-1- (3. {[[(2-methylpyridin-3-yl) oxy] methyl] pyrimidin-1-yl) phthalazine; 5,6,7-trimethoxy-1 - (3. {[[(6-methylpyridin-3-yl) oxy] methyl) piperidin-1-yl) phthalazine; 3-. { [1- (5,6,7-Tr! Methoxyphthalazin-1-yl) p, ppern-3-yl] methoxy} pyridin-2-amine; 3 - [(2-methyl-1H-imidazol-1-yl) methyl] -1 - (5,6,7-trimethoxy-phthalazin-1-yl) p -peridin-3-ol; 5,6,7-trimethoxy-1-. { 4- [5- (methoxymethyl) -1,4,4-oxadiazol-2-yl] piperidin-1-yl} phthalazine; 1- [4- (5-butyl-1, 3,4-oxadiazol-2-yl) piperidin-1-yl] -5,6,7-trimethoxyphthalazine; 1- [3- (5-cyclopropyl-1, 3,4-oxadiazol-2-yl) piperidin-1-yl] -5,6,7-trimethoxyphthalazine; 5,6,7-trimethoxy-1-. { 3- [5- (methoxymethyl) -1,4,4-oxadiazol-2-yl] pyridin-1-yl} phthalazine; N, N-dimethyl-1-. { 5- [1 - (5,6,7-Tr ~ methoxyptalazin-1-yl) p, peridin-3-yl] -1, 3,4-oxadiazol-2-yl} Methanamine 5,6,7-trimethoxy-1 -. { 4 - [(6-methy1pyridazin-3-yl) methyl] piperidin-1-ylphthalazine; 5,6,7-trimethoxy-1- [4- (pyrimidin-2-ylmethyl) pyridin-1-yl] phthalazine; 3- (1 H -prrazol-1-ylmethyl) -1 - (5,6,7-trimethoxyptalazin-1-yl) piperidin-3-ol; 5,6,7-trimethoxy-1 - [4- (2-methylpyrimidin-4-yl) piperidin-1-yl] phthalazine; 5,6,7-trimethoxy-1- [3- (pyridin-2-ylmethyl) piperidin-1- I Phthalazine; 5,67-trimethoxy-1- [3- (pyridin-2-ylmethyl) piperidin-1-yl] phthalazine; (3- {[[1- (5,6,7-trimethoxyptalazin-1-yl) piperidin- 3-yl] methyl.} Phenyl) methanol; 5,6,7-trimethoxy-1 -. { 3- [2- (methoxymethyl) pyrimidin-4-yl] p, peridn-1-yl} phthalazin! 5,6,7-trimethoxy-1- (3-pyrimidin-4-ylpiperidin-1-yl) phthalazine; N-ethyl-4- [1- (5,6,7-trimethoxy-phthalazin-1-yl) piperidin-4-yl] pyrimidin-2-amine 5,6,7-trimethoxy-1 - (4-pyrimidin-4-ylpiperidin-1-yl) phthalazine; 4 - [(2-methy1-1 H -amidazol-1-yl) meth] -1- (5,6,7-tr'methoxyphthalazin-1-yl) piperidin-4- ol; 5.6 J-tr¡methoxy-1- (4- [1, 2,4] triazolo [15-a] pyrimid-7-pyridin-1-yl) phthalazine; 1- [4- (2-cyclopropyl-pyrimidin-4-yl) piperidin-1-yl] -5,6,7-trimethoxyptalazine; 1- [4- (5-cyclopropyl-1, 3,4-oxadiazol-2-yl) pipendin-1-yl] -5,6,7-trimethoxyphthalazine; 5,6,7-trimethoxy-1- [4- (pyrazin-2-ylmethyl) piperidin-1-yl] phthalazine; 3- [1 - (5,6,7-trimethoxyptalazin-1-yl) piperidin-4-yl] benzamide; 4- [1 - (5,6,7-trimethoxyptalazin-1-yl) piperidin-4-yl] benzamide, 5,6,7-trimethoxy-1- (4-pyrimidin-2-ylpiperidin-1 - il) phthalazine; 1 - [3- (3-Chlorobenzyl) piperidin-1-yl] -5,6,7-trimethoxyptalazine; 5,6,7-trimethoxy-1- [3- (pyrimidin-5-ylmethyl) piperidin-1-yl] phthalazine; N, N-dimethyl-4- [1 - (5,6,7-tnmethoxyptalazin-1-yl) piperidin-4-yl] pyrimidin-2-amine 5,6,7-trimethoxy-1- [4- (pyrimidine -5-ylmethyl) piperidin-1-yl] phthalazine; 1- [3- (1 H-benzimidazol-2-yl) piperidin-1-yl] -5,6,7-trimethoxyphthalazine; 1- [4- (4-fluorobenzyl) piperidin-1-yl] -5,6,7-trimethoxyptalazine; 5,6,7-trimethoxy-1- [3- (3-methylphenyl) piperidin-1-yl] phthalazine; 1- [4- (2-fluorobenzyl) piperidin-1-yl] -5,6,7-trimethoxyptalazine; 5,6,7-trimethoxy-1 -. { 3 - [(2-methyl-1 H-imidazol-1-yl) methyl] piperidin-1-yl} phthalazine; 5,6,7-trimethoxy-1- [4- (1 H -pyrazol-1-ylmethyl) piperidin-1-yl] phthalazine; 1- [4- (3-cyclopropyl-1, 2,4-oxadiazol-5-yl) piperidin-1-yl] -5,6,7-trimethoxyphthalazine; 1- [3- (5-cyclopropyl-4H-1, 2,4-triazol-3-yl) piperidin-1-yl] -5,6,7-trimethoxyptalazine; 4- (2-fluoro-5-methylphenyl) -1 - (5,6,7- tr, methoxyphthalazin-1-yl) p, per, d, n-4-ol; 1 - [4- (2-fluorophenoxy) piperidn-1-yl] -5,6,7-trimethoxyphthalazine; 1-. { 3 - [(4-fluorophenoxy) methyl] piperidin-1-yl} -5,6,7-trimethoxyphthalazine; 5,6,7-trimethoxy-1- [4- (pyridin-2-methoxy) pperidin-1-yl] phthalazine; 5,67-tnmethoxy-1 -. { 4- [5- (methoxymethyl) -1,4, 2,4-oxadiazol-3-yl] pipendin-1-yl} phthalazine; 5,6 J-trimethoxy-1 - [4- (3-methoxy-phenyl) p -peridin-1-yl] phthalazine; 1 - [4- (3,5-difluorophenyl) piperid n-1-yl] -5,6,7-tr'methoxyptalazine-1- [4- (3-fluorophenoxy) pperiod-1-yl] -5,6,7- trimetoxytalazine; 1 - [4- (4-fluorophenoxy) piperidin-1-yl] -5,6,7-trimethoxyptalazine; 4- [1 - (5,6,7-Tr! Methoxyphthalazin-1-l) piperidin-4-yl] benzonitrile 1 '- (5,6,7-tr¡methoxyftalaz) n-1-yl) spiro [chromene-24'-p, peridin] 1- [3- (1 H-imidazol-2-yl) p, peridin-1-yl] -5,6, 7-Trimethoxy-3-trifluoro-1 '- (5,6,7-trimethoxyptalazin-1-yl) -34-d, hi-drospiro [socromen-14'-piperidine] N- [1- (5,6 , 7-trimethoxyptalazin-1-yl) pyrimidin-4-yl] pyrimidn-2-amine N- [1- (5,6,7-trimethoxyptalazin-1-yl) piper d, n-4-yl] pyridyl-2-amino N-benzyl-N-methyl-1- (5,6,7-trimethoxy-3-yla-1-yl) piperidin-4-amine 5,6 , 7-trimethoxy-1 - [4- (4-methylbenzyl) p.perddin-1-yl] phthalazine; 1- [4- (4-chlorophenyl) -4-methylpipendin-1-yl] -5,6,7-tnmethoxyptalazine; 1 '- (5,6,7-trimethoxyptalazin-1-yl) spiro [indole-34'-piperidin] -2 (1 H) -one; and its pharmaceutical salts. 12 - A pharmaceutical composition useful for treating psychotic disorders, hallucinatory disorders and drug-induced psychosis, anxiety disorders, movement disorders, mood disorders, neurodegenerative disorders and drug addiction, comprising an amount of a compound of Formula I according to with claim 1 effective in the treatment of said disorder or condition. 13. - The use of a compound of formula I as claimed in claim 1, for the preparation of a medicament useful for the treatment of a disorder selected from psychotic disorders, hallucinatory disorders and drug-induced psychosis, anxiety disorders, disorders of movement, mood disorders and neurodegenerative disorders. 14. The use as claimed in claim 3, wherein said disorder is selected from the group consisting of: dementia, Alzheimer's disease, multi-infarct dementia, alcoholic dementia or other drug-related dementia, dementia associated with intracranial tumors or trauma brain, dementia associated with Huntington's disease or Parkinson's disease, or AIDS-related dementia; delirium; amnestic disorder; post-traumatic stress disorder; Mental retardation; a learning disorder, for example, reading disorder, math disorder, or a written expression disorder; hyperactivity disorder with attention deficit; cognitive impairment related to age, major depressive episode of mild, moderate or severe type, an episode of manic or mixed mood; an episode of hypomanic mood; a depressive episode with atypical features; a depressive episode with melancholic characteristics; a depressive episode with catatonic characteristics; an episode of mood with beginning after childbirth; depression after stroke; major depressive disorder; dysthymic disorder; minor depressive disorder; premenstrual dysphoric disorder; post-psychotic depressive disorder schizophrenia; a major depressive disorder superimposed on a psychotic disorder comprising a hallucinatory disorder or schizophrenia; a bipolar disorder comprising bipolar I disorder, bipolar II disorder, cyclothymic disorder, Parkinson's disease, Huntington's disease; dementia, Alzheimer's disease, multi-infarct dementia, AIDS-related dementia, frontotemporal dementia; neurodegeneration associated with cerebral trauma; neurodegeneration associated with stroke, neurodegeneration associated with cerebral infarction; neurodegeneration induced by hypoglycaemia; neurodegeneration associated with epileptic seizure; neurodegeneration associated with neurotoxin poisoning; multisystemic, paranoid, disorganized, catatonic, undifferentiated or residual atrophy; schizophreniform disorder; schizoaffective disorder of the hallucinatory or depressive type; hallucinatory disorder, substance-induced psychotic disorder, psychosis induced by alcohol, amphetamine, cannabis, cocaine, hallucinogens, inhalants, opioids, or phencyclidine; Paranoid type personality disorder; and personality disorder of schizoid type.