WO2006000902A1

WO2006000902A1 - Dihydrobenzofuran compounds and uses thereof

Info

Publication number: WO2006000902A1
Application number: PCT/IB2005/001853
Authority: WO
Inventors: Yuan-Ching Phoebe Chiang
Original assignee: Pfizer Products Inc.
Priority date: 2004-06-25
Filing date: 2005-06-13
Publication date: 2006-01-05

Abstract

Dihydrobenzofuran compounds of Formula (I), including salts, prodrugs, hydrates and solvates thereof, that act as 5-HT2 receptor ligands and their uses in the treatment of diseases linked to the activation of 5-HT2 receptors in animals are described herein. Formula (I).

Description

DIHYDROBENZOFURAN COMPOUNDS AND USES THEREOF

FIELD OF THE INVENTION The present invention relates to dihydrobenzofuran compounds. The dihydrobenzofuran compounds have been found to act as 5-HT receptor ligands, in particular 5-HT_2c receptor agonists and 5- HT_2a receptor antagonists; therefore, the present invention also relates to their uses in the prevention or treatment of diseases linked to the activation of the 5-HT_2c receptor and/or blocking of the 5-HT_2a receptor in animals. BACKGROUND Receptors for serotonin (5-hydroxytryptamine, 5-HT) are an important class of G protein-coupled receptors. Serotonin is thought to play a role in processes related to learning and memory, sleep, thermoregulation, mood, motor activity, pain, sexual and aggressive behaviors, appetite, neurodegenerative regulation, and biological rhythms. As expected, serotonin is linked to pathophysiological conditions such as anxiety, depression, obsessive-compulsive disorders, schizophrenia, suicide, autism, migraine, emesis, alcoholism and neurodegenerative disorders. The serotonin receptors are currently classified into seven subfamilies (5-HT₁ through 5-HT₇). See, Hoyer, D., et al., "VlI International Union of Pharmacology classification of receptors for 5- hydroxytryptamine", Pharmacol. Rev., 56, 157-203 (1994). The subfamilies have been further divided into subtypes. For example, the 5-HT₂ receptor is currently divided into three subtypes: 5-HT_2a, 5-HT_2b and 5- HT_2c. The three subtypes of 5-HT₂ receptors are linked to phospholipase C with the generation of two second messengers, diacylglycerol (which activates protein kinase C) and inositol trisphosphate (which releases intracellular stores of Ca²⁺). The 5-HT_2c receptors have a very high density in the choroid plexus, an epithelial tissue that is the primary site of cerebrospinal fluid production. See, Sanders-Bush, E. and S. E. Mayer, "5-Hydroxytryptamine (Serotonin) Receptor agonists and Antagonists", Goodman & Gilman's The Pharmacological Basis of Therapeutics, Chapter 11 , 9^th Ed., McGraw-Hill, New York, NY (1996). Julius, et al., isolated and characterized the 5-HT_2c receptor and later reported that transgenic mice lacking the 5-HT_2c receptor exhibit seizures and an eating disorder resulting in increased consumption of food (see, U.S. Patent Nos. 4,985,352 and 5,698,766, respectively). Consequently, compounds selective for the 5-HT_2c receptor may provide useful therapies for the treatment of seizure and eating disorders without the side effects typically associated with nonselectivity of the ligand. Several compounds have been proposed as 5-HT_2c receptor agonists or antagonists for use in the treatment of obesity and other related diseases associated with decreased neurotransmission of serotonin in mammals. See, e.g., EP 863136 (azetidine and pyrrolidine derivatives); EP 657426 (tricyclic pyrrole derivatives); EP 655440 (substituted 1-aminoethyl indoles); EP 572863 (pyrazinoindole derivatives); WO98/030548 (aminoalkylindazole compounds); WO 98/56768 (tricyclic pyrrole and pyrazole derivatives); WO 99/43647 (azetidine and pyrrolidine derivatives); WO 99/58490 (aryl-hydronaphthalenalkanamine derivatives); WO 00/12475 (indoline derivatives); WO 00/12482 (indazole derivatives); WO 00/12502 (pyrroloquinoline derivatives); WO 00/12510 (pyrroloindole, pyridoindole and azepinoindole derivatives); WO 00/28993 (naphthylacetylpiperazine derivatives); WO 00/44737 (aminoalkylbenzofuran derivatives); WO 00/76984 (2,3-disubstituted pyrazines); US Publication No. 2002/0147200 A1 or WO 02/40456 (pyrazine, pyridine, and pyrimidine derivatives); WO 03/000666 (pyrazine derivatives); and US Publication No. 2003/0105106 A1 or WO 03/000663 (pyrimidine derivatives). For a recent review of obesity medications, see A. Halpern and M. C. Mancini, "Treatment of obesity: an update on anti-obesity medications," Obesity Reviews. 4, 25-42 (2003). Toxicity and non-selectivity of ligands for the various 5-HT receptors remain a challenge. It is suspected that the non-selectivity of some ligands contributes to various adverse side effects such as hallucinations and cardiovascular complications. Therefore, there remains a need for 5-HT_2c selective receptor ligands. SUMMARY The present invention provides compounds of Formula (I). The compounds of Formula (!) have been found to be useful as 5-HT₂ receptor ligands (in particular, 5-HT_2a and 5-HT_2c receptor ligands).

(I)¹ wherein; R^1a is hydrogen or (Ci-C₄)alkyl, or R^1a taken together with R^1b forms a 5- to 10-membered partially or fully saturated heterocyclic ring containing one to two additional N atoms, where said heterocyclic ring is optionally substituted with one or more independently selected from the group consisting of fluoro, (Ci-C₄)alkyl, fluoro-substituted (Ci-C₄)alkyl, and fluoro-substituted(CrC₄)alkoxy; R^1b is (i) hydrogen, (ii) a partially or fully saturated 3- to 6-membered carbocyclic ring, (iii) a partially or fully saturated 4- to 8-membered heterocyclic ring containing one to two heteroatoms selected from O, N or S, or (iv) a (CrC₈)alkyl optionally substituted with one or more substituents independently selected from the group consisting of an optionally substituted phenyl, an optionally substituted 5- to 6-membered heteroaryl, (CrC₆)alkylamino, di(C_rC₆)alkylamino, 3- to 8-membered partially or fully saturated carbocyclic ring, and 4- to 7-membered partially or fully saturated heterocyclic ring containing one to three heteroatoms independently selected from O, N and S, provided that R^1b is not a (C-i-C₆)alkyl substituted with a group selected from phenyl, an optionally substituted pyridyl, or an optionally substituted thiophene; n is 1 , 2 or 3 (preferably, n is 1 or 2, more preferably, n is 1 ); R² is hydrogen; R³ is (i) hydrogen, (ii) a (Ci-C₆)alkyl optionally substituted with one or more substituents independently selected from the group consisting of (CrC₆)alkoxy, halo, fluoro-substituted (C₁- C₄)alkyl, fluoro-substituted(C_rC₄)alkoxy, amino, (C₁-C₆) alkylamino, di(C_r C₆)alkylamino, 3- to 8-membered partially or fully saturated carbocyclic ring, and 3- to 8-membered heterocyclic ring containing 1 to 2 heteroatoms independently selected from O, N or S, (iii) a 3- to 8-membered partially or fully saturated carbocyclic ring, (iv) a 5- to 6-membered heteroaryl containing 1 to 2 heteroaroms independently selected from O, N or S, a 4- to 8-membered heterocyclic ring containing 1 to 2 heteroatoms independently selected from O, N or S, or (v) a phenyl group optionally substituted with one or more substitutents independently selected from the group consisting of halo, (C_rC₆)alkyl, fluoro-substituted (C_rC₄)alkyl, (C_rC₄)alkoxy, and fluoro-substituted(C_rC₄)alkoxy; R⁴ and R⁵ are each independently hydrogen, or (Ci-C₆)alkyl; R⁶, R⁷, R⁸ and R⁹ are each independently selected from the group consisting of hydrogen, (C₁- C₈)alkyl, (C_rC₈)alkyl-R¹¹, fluoro-substituted (C_rC₄)alkyl, cyano, halo, -NHC(O)-(C₁-C₄)alkyl, (C₁- C₆)alkoxy, fluoro-substituted (C_rC₄)alkoxy, aryloxy, heteroaryloxy, a 3- to 8-membered partially or fully saturated carbocyclic ring, a 4- to 8-membered heterocyclic ring containing 1 to 2 heteroatoms independently selected from O, N or S, a phenyl substituted with one or more substituents independently selected from R¹¹, or a 5- to 10-membered heteroaryl containing 1 to 3 heteroatoms independently selected from O, S or N, where said aryloxy, said heteroaryl and said heteroaryloxy are optionally substituted with one or more substituents independently selected from R¹¹, provided that at least one of R⁶, R⁷, R⁸ and R⁹ is other than hydrogen, or R⁸ and R⁹ taken together form a partially or fully saturated 5- to 9-membered carbocyclic ring or a 4- to 8-membered heterocyclic ring containing 1 to 3 heteroatoms independently selected from O, N and S, or R⁸ and R⁹ taken together form a fused 6-membered aromatic ring or a fused 5- to 6-membered heteroaromatic ring containing 1 to 2 heteroatoms selected from O, N or S; R¹⁰ is (C₃-C₆)cycloalkyl, or 4- to 8-membered partially or fully saturated heterocycle containing 1 to 3 heteroatoms selected from O, N or S aryl, or heteroaryl containing 1 to 3 heteroatoms selected from O, N or S; R¹¹ is halo, cyano, (CrC^alkyl, fluoro-substituted (C_rC₄)alkyl, fluoro-susbsituted (C₁-C₄JaIkOXy, aryl, heteroaryl, (Ci-C₆)alkylamino(CrC₆)alkyl, di(C₁-C₆)alkylamino(C₁-C₆)alkyl, acyl, acylamino, aminoacyl, (C_rC₆)alkylaminoacyl, di(CrC₆)alkylaminoacyl, (C_rC₆)alkylsulfonamido, arylsulfonamido, - 0R^11a, -SR^11a, -SOR^11a, or -SO₂R^11a, where R^11a is (C_rC₆)alkyl, -CF₃, a 3- to 8-membered fully saturated carbocyclic ring, or 4- to 10-membered partially or fully saturated heterocyclic ring containing 1 to 3 heteroatoms selected from O, N or S, a pharmaceutically acceptable salt thereof, a prodrug of the compound or the salt, or a solvate or hydrate of the compound, the prodrug, or the salt. When R^1a is hydrogen or (Ci-C₄)alkyl, then R^1b is preferably (i) hydrogen, (ii) a fully saturated 3 to 6-membered carbocyclic ring, (iii) a fully saturated 4 to 8-membered heterocyclic ring containing one to two N atoms, or (iv) a (C_rC₆)alkyl optionally substituted with one or more substituents independently selected from the group consisting of (CrC₄)alkylamino, 3 to 6-membered fully saturated carbocyclic ring, and 4 to 8-membered fully saturated heterocyclic ring containing a N atom; More preferably, R^1b is hydrogen, (C_rC₄)alkyl, or a 3 to 4-membered fully saturated carbocyclic ring. Most preferably, R^1b is hydrogen or (CrC₄)alkyl. R⁴ and R⁵ are both preferably hydrogen. Preferably, R⁶, R⁷, R⁸, R⁹ are each independently selected from the group consisting of hydrogen, (C_rC₆)alkyl, fluoro-substituted (C_rC₄)alkyl, cyano, halo, (C_rC₆)alkoxy, fluoro-substituted (C_rC₄)alkoxy. aryloxy, a 3- to 8-membered fully saturated carbocyclic ring, a fully saturated 4- to 8-membered heterocyclic ring, a phenyl substituted with one to three substituents independently selected from R¹¹, a 5- 10-membered heteroaryl containing 1 to 3 heteroatoms independently selected from O, S, or N where said aryloxy and said heteroaryl is optionally substituted with one or more substituents selected from the group consisting of halo, cyano, (C_rC₆)alkyl, fluoro-substituted (Ci-C₄)alkyl, fluoro-substituted (C₁- C₄)alkoxy, acylamino, and aminoacyl, or R⁸ and R⁹ taken together form a partially or fully saturated 5- to 6- membered carbocyclic ring or a 4- to 8-membered partially or fully saturated heterocyclic ring containing 1-3 heteroatoms independently selected from O, N, or S. In another preferred embodiment, R⁶, R⁷, and R⁸ are hydrogen; and R⁹ is a phenyl substituted with one or more substituents independently selected from halo, cyano, (Ci-C₆)alkyl, fluoro-substituted (CrC₄)alkyl, and fluoro-susbsituted (Ci-C₄)alkoxy. Preferred compounds include: C-(5-chloro-7-o-tolyl-2,3-dihydro-benzofuran-2-yl)-methylamine; C-[7-(2-chloro-phenyl)-5-methyl-2,3-dihydro-benzofuran-2-yl]-methylamine; C-[5-chloro-7-(2-chloro- phenyl)-2,3-dihydro-benzofuran-2-yl]-methylamine; C-[5-chloro-7-(2-fluoro-phenyl)-2,3-dihydro- benzofuran-2-yl]-methylamine; C-(6,7-dimethyl-2,3-dihydro-benzofuran-2-yl)-methylamine; C-(7-chloro-6- trifluoromethyl-2,3-dihydro-benzofuran-2-yl)-methylamine; C-(6,7-dichloro-2,3-dihydro-benzofuran-2-yl)- methylamine; C-(2,3,6,7,8,9-hexahydro-naphtho[1 ,2-b]furan-2-yl)-methylamine; C-(5-chloro-2,3,6,7,8,9- hexahydro-naphtho[1 ,2-b]furan-2-yl)-methylamine; C-(3,6,7,8-tetrahydro-2H-1-oxa-as-indacen-2-yl)- methylamine; and methyl-(3,6,7,8-tetrahydro-2H-1 -oxa-as-indacen-2-ylmethyl)-amine; 3-(2-aminomethyl- 2,3-dihydro-benzofuran-7-yl)-benzonitrile; C-[7-(3-methoxy-phenyl)-2,3-dihydro-benzofuran-2-yl]- methylamine; C-[7-(3-fluoro-phenyl)-2,3-dihydro-benzofuran-2-yl]-methylamine; C-[7-(4-methoxy- phenyl)-2,3-dihydro-benzofuran-2-yl]-methylamine; C-[7-(2,4-difluoro-phenyl)-2,3-dihydro-benzofuran-2- yl]-methylamine; C-[7-(2,3-dichloro-phenyl)-2,3-dihydro-benzofuran-2-yl]-methylamine; C-[7-(4-fluoro- phenyl)-2,3-dihydro-benzofuran-2-yl]-methylamine; C-[7-(5-chloro-2-methoxy-phenyl)-2,3-dihydro- benzofuran-2-yrj-methylamine; 4-(2-aminomethyl-2,3-dihydro-benzofuran-7-yl)-benzonitrile; C-[7-(2- chloro-phenyl)-2,3-dihydro-benzofuran-2-yl]-methylamine; C-[7-(2-fluoro-phenyl)-2,3-dihydro-benzofuran- 2-yl]-methylamine; C-(7-o-tolyl-2,3-dihydro-benzofuran-2-yl)-methylamine; C-[7-(2-trifluoromethyl- phenyl)-2,3-dihydro-benzofuran-2-yl]-methylamine; C-[7-(2,5-dichloro-phenyl)-2,3-dihydro-benzofuran-2- yl]-methylamine; C-[7-(2,4,6-trimethyl-phenyl)-2,3-dihydro-benzofuran-2-yl]-methylamine; C-[7-(4-chloro- phenyl)-2,3-dihydro-benzofuran-2-yl]-methylamine; and C-(7-p-tolyl-2,3-dihydro-benzofuran-2-yl)- methylamine; (R) C-[7-(2-chloro-phenyl)-2,3-dihydro-benzofuran-2-yl]-methylamine; (S) C-[7-(2-chloro- phenyl)-2,3-dihydro-benzofuran-2-yl]-methylamine; (R) C-[7-(2-fiuoro-phenyl)-2,3-dihydro-benzofuran-2- yl]-methylamine; (R) C-(7-o-tolyl-2,3-dihydro-benzofuran-2-yl)-methylamine; (R) C-[7-(2-trifluoromethyl- phenyl)-2,3-dihydro-benzofuran-2-yl]-methylamine; (R) C-[7-(2,5-dichloro-phenyl)-2,3-dihydro-benzofuran- 2-yl]-methylamine; (R) C-[7-(2,4,6-trimethyl-phenyl)-2,3-dihydro-benzofuran-2-yl]-methylamine; (R) C-[7- (4-chloro-phenyl)-2,3-dihydro-benzofuran-2-yl]-methylamine; (S) C-[7-(4-chloro-phenyl)-2,3-dihydro- benzofuran-2-yl]-methylamine; and (R) C-(7-p-toIyl-2,3-dihydro-benzofuran-2-yl)-methylamine; a pharmaceutically acceptable salt of the compound, or a solvate or hydrate of the compound or the salt. When R^1a is taken together with R^1b to form a 5- to 10-membered partially or fully saturated heterocyclic ring containing one to two additional N atoms, where said heterocyclic ring is optionally substituted with one or more independently selected fluoro, (Ci-C₄)alkyl, fluoro-substituted (C_rC₄)alkyl, and fluoro-substituted(CrC₄)alkoxy, then R⁴ and R⁵ are preferably both hydrogen; and R⁶, R⁷, R⁸, R⁹ are each independently selected from the group consisting of hydrogen, (C_rC₆)alkyl, fluoro-substituted (C₁- C₄)alkyl, cyano, halo, (Ci-C₆)alkoxy, fluoro-substituted (C_rC₄)alkoxy. aryloxy, a 3- to 8-membered fully saturated carbocyclic ring, a fully saturated 4- to 8-membered heterocyclic ring, a phenyl substituted with one to three substituents independently selected from R¹¹, a 5-10-membered heteroaryl containing 1 to 3 heteroatoms independently selected from O, S, or N where said aryioxy and said heteroaryl is optionally substituted with one or more substituents selected from the group consisting of halo, cyano, (CrC^alkyl, fluoro-substituted (C_rC₄)alkyl, fluoro-substituted (C₁-C₄JaIkOXy, acylamino, and aminoacyl, or R⁸ and R⁹ taken together form a partially or fully saturated 5- to 6- membered carbocyclic ring or a 4- to 8-membered partially or fully saturated heterocyclic ring containing 1-3 heteroatoms independently selected from O, N, or S; a pharmaceutically acceptable salt of the compound, or a solvate or hydrate of the compound or the salt. In another preferred embodiment, R⁶, R⁷, and R⁸ are preferably hydrogen; and R⁹ is preferably a phenyl substituted with one or more substituents independently selected from halo, cyano, (C_rC₆)alkyl, fluoro-substituted (C_rC₄)alkyl, (C_rC₄)aikoxy, and fluoro-susbsituted (C_rC₄)alkoxy; a pharmaceutically acceptable salt of the compound, or a solvate or hydrate of the compound or the salt. Preferred compounds of this embodiment include: 1-[7-(2-chloro-phenyl)-2,3-dihydro-benzofuran- 2-ylmethyl]-piperazine; 1-[7-(3-chloro-phenyl)-2,3-dihydro-benzofuran-2-ylmethyl]-piperazine; 1-[7-(2- fluoro-phenyl)-2,3-dihydro-benzofuran-2-ylmethyl]-piperazine; 1-[7-(3-fluoro-phenyl)-2,3-dihydro- benzofuran-2-ylmethyl]-piperazine; 1-(7-o-tolyl-2,3-dihydro-benzofuran-2-ylmethyl)-piperazine; 1-(7-m- tolyl-2,3-dihydro-benzofuran-2-y!methyl)-piperazine; 1-[7-(2,5-dichloro-phenyl)-2,3-dihydro-benzofuran-2- ylmethyl]-piperazine; 3-(2-piperazin-1-ylmethyl-2,3-dihydro-benzofuran-7-yl)-benzonitrile; and 1-[7-(2,3- dichloro-pheny!)-2,3-dihydro-benzofuran-2-ylmethyl]-piperazine; a pharmaceutically acceptable salt of the compound, or a solvate or hydrate of the compound or the salt. Another embodiment of the present invention includes a pharmaceutical composition comprising (1) a compound of the present invention, and (2) a pharmaceutically acceptable excipient, diluent, or carrier. Preferably, the composition comprises a therapeutically effective amount of a compound of the present invention. The composition may also contain at least one additional pharmaceutical agent (described herein). Preferred agents include nicotine receptor partial agonists, opioid antagonists (e.g., naltrexone and nalmefene), dopaminergic agents (e.g., apomorphine), attention deficit disorder ((ADD) including attention deficit hyperactivity (ADHD)) agents (e.g., Ritalin™, Strattera™, Concerta™ and Adderall™), anti-psychotic agents (e.g., ziprasidone, risperidone, olanzapine, quetiapine, clozapine, haloperidol, and pharmaceutically acceptable salts thereof) and anti-obesity agents (described herein below which include agents that promote weight loss or weight maintenance). Yet another embodiment of the present invention includes a method for treating 5-HT₂ (preferably, 5-HT₂₀ and 5-HT_2a) receptor-mediated diseases, conditions, or disorders in animals comprising the step of administering to an animal in need of such treatment a therapeutically effective amount of a compound of the present invention (or a pharmaceutical composition thereof). Diseases, conditions, and/or disorders modulated by 5-HT₂ receptor ligands include eating disorders (e.g., binge eating disorder, anorexia, and bulimia), weight loss or control (e.g., reduction in calorie or food intake, and/or appetite suppression), obesity, depression, atypical depression, bipolar disorders, psychoses, schizophrenia, behavioral addictions, suppression of reward-related behaviors (e.g., conditioned place avoidance, such as suppression of cocaine- and morphine-induced conditioned place preference), substance abuse, addictive disorders, impulsivity, alcoholism (e.g., alcohol abuse, addiction and/or dependence including treatment for abstinence, craving reduction and relapse prevention of alcohol intake), tobacco abuse (e.g., smoking addiction, cessation and/or dependence including treatment for craving reduction and relapse prevention of tobacco smoking), premenstrual syndrome or late luteal phase syndrome, migraine, panic disorder, anxiety, post-traumatic syndrome, dementia (including memory loss, Alzheimer's disease, dementia of aging, vascular dementia, mild cognitive impairment, age-related cognitive decline, and mild neurocognitive disorder), sexual dysfunction (male and female), seizure disorders, epilepsy, gastrointestinal disorders (e.g., dysfunction of gastrointestinal motility or intestinal propulsion), attention deficit disorders or attention deficit hyperactivity disorders (ADD/ADHD), disruptive behavior disorders, impulse control disorders, borderline personality disorder, obsessive compulsive disorder, chronic fatigue syndrome, anorexia nervosa, disorders of sleep (e.g., sleep apnea), autism, epilepsy, mutism, spinal cord injury, damage of the central nervous system (e.g., trauma, stroke, neurodegenerative diseases or toxic or infective CNS diseases (e.g., encephalitis or meningitis)), cardiovascular disorders (e.g., thrombosis), Parkinson's disease, diabetes insipidus, and type Il diabetes. In a preferred embodiment, the method is used in the treatment of eating disorders, obesity, sexual dysfunction (male and female), anxiety, depression, and psychosis. One aspect of the present invention is a method for treating obesity or controlling weight gain (including reducing or maintaining weight) comprising the step of administering to an animal in need of such treatment or control a therapeutic amount of a compound of the present invention (or pharmaceutical composition thereof). Another aspect of the present invention is a method for treating psychosis (e.g., schizophrenia and related disorders) comprising the step of administering to an animal in need of such treatment a therapeutic amount of a compound of the present invention (or pharmaceutical composition thereof). Yet Another aspect of the present invention is a method for treating female sexual dysfunction (FSD) comprising the step of administering to a female in need of such treatment a therapeutically effective amount of a compound of the present invention (or pharmaceutical composition thereof). The method may further include the administration of one or more additional pharmaceutically active agents for treating FSD (see, e.g., the preferred list of agents below). The FSD treatments include female sexual arousal disorder (FSAD), female orgasmic disorder (FOD), hypoactive sexual desire disorder (HSDD), or sexual pain disorder. In yet another aspect of the present invention, a method is provided for treating male erectile dysfunction (MED) comprising the step of administering to a male in need of such treatment a therapeutically effective amount of a compound of the present invention (or pharmaceutical composition thereof). Compounds of the present invention may be administered in combination with other pharmaceutical agents (e.g., anti-obesity agents, anti-pyschotic agents, and agents used for treating sexual dysfunction). Preferred anti-obesity agents include apo-B/MTP inhibitors, 11 β-hydroxy steroid dehydrogenase-1 (11β-HSD type 1) inhibitors, PYY_3-36 and analogs thereof, MCR-4 agonists, CCK-A agonists, monoamine reuptake inhibitors, sympathomimetic agents, β₃ adrenergic receptor agonists, dopamine receptor agonists, melanocyte-stimulating hormone receptor analogs, cannabinoid 1 receptor antagonists (e.g., rimonabant), melanin concentrating hormone receptor antagonists, ieptin, leptin analogs, leptin receptor agonists, galanin receptor antagonists, lipase inhibitors, bombesin receptor agonists, neuropeptide-Y receptor antagonists (e.g., NPY Y5 receptor antagonists such as those described hereinbelow), thyromimetic agents, dehydroepiandrosterone or analogs thereof, glucocorticoid receptor antagonists, orexin receptor antagonists, glucagon-like peptide-1 receptor agonists, ciliary neurotrophic factors, human agouti-related protein antagonists, ghrelin receptor antagonists, histamine 3 receptor antagonists or inverse agonists, and neuromedin U receptor agonists, and the like. Preferred anti-psychotic agents include ziprasidone (e.g., GEODON®), risperidone (e.g., RISPERDAL®), olanzapine (e.g., ZYPREXA®), quetiapine (e.g., SEROQUEL®), clozapine (e.g., CLOZARIL®), haloperidol (e.g., HALDOL®) and pharmaceutically acceptable salts thereof. Preferred additional agents used in treating female sexual dysfunction include: (1 ) estrogen receptor modulators (e.g., estrogen agonists, estrogen antagonists or combinations thereof); (2) testosterone replacement agents, testosternone (Tostrelle), dihydrotestosterone, dehydroepiandrosterone (DHEA), a testosterone implant, or combinations thereof; (3) estrogen, a combination of estrogen and medroxyprogesterone or medroxyprogesterone acetate (MPA), or a combination of estrogen and a methyl testosterone hormone replacement therapy agent; (4) one or more dopaminergic agents (e.g. D2, D3 or D4 agents); (5) one or more of an NPY (neuropeptide Y) inhibitor (e.g., NPY-1 and NPY-5 inhibitors); (6) one or more of a melanocortin receptor modulator or melanocortin enhancer; (7) one or more of an NEP inhibitor; (8) one or more of a PDE inhibitor; and (9) one or more of a bombesin receptor modulator. Preferred additional pharmaceutical agents used in treating male sexual dysfunction (e.g., male erectile dysfunction) include dopaminergic agents, NPY-1 inhibitors, NPY-5 inhibitors, melanocortin receptor modulators, melanocortin enhancers, NEP inhibitors, cGMP PDE-5 inhibitors, bombesin receptor modulators, and mixtures thereof. The combination therapy may be administered as (a) a single pharmaceutical composition which comprises a compound of the present invention, at least one additional pharmaceutical agent described herein and a pharmaceutically acceptable excipient, diluent, or carrier; or (b) two separate pharmaceutical compositions comprising (i) a first composition comprising a compound of the present invention and a pharmaceutically acceptable excipient, diluent, or carrier, and (ii) a second composition comprising at least one additional pharmaceutical agent described herein and a pharmaceutically acceptable excipient, diluent, or carrier. The pharmaceutical compositions may be administered simultaneously or sequentially and in any order. Yet another aspect of the present invention includes a pharmaceutical kit for use by a consumer to treat diseases, conditions, and/or disorders modulated by 5-HT₂ receptor ligands in an animal. The kit comprises a) a suitable dosage form comprising a compound of the present invention; and b) instructions describing a method of using the dosage form to treat diseases, conditions or disorders that are modulated by 5-HT₂ receptor agonists or antagonists (in particular, 5-HT_2c agonists and/or 5-HT_2a antagonists). Another embodiment includes a pharmaceutical kit comprising: a) a first dosage form comprising (i) a compound of the present invention and (ii) a pharmaceutically acceptable carrier, excipient or diluent; b) a second dosage form comprising (i) an additional pharmaceutical agent described herein, and (ii) a pharmaceutically acceptable carrier, excipient or diluent; and c) a container. Definitions As used herein, the term "alkyl" refers to a hydrocarbon radical of the general formula C_nH_2n+-_I. The alkane radical may be straight or branched. For example, the term "(CrC₆)alkyl" refers to a monovalent, straight, or branched aliphatic group containing 1 to 6 carbon atoms (e.g., methyl, ethyl, n- propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, neopentyl, 3,3-dimethylpropyl, hexyl, 2-methylpentyl, and the like). Similarly, the alkyl portion (i.e., alkyl moiety) of an alkoxy, acyl (e.g., alkanoyl), alkylamino, dialkylamino, and alkylthio group have the same definition as above. When indicated as being "optionally substituted", the alkane radical or alkyl moiety may be unsubstituted or substituted with one or more substituents (generally, one to three substituents except in the case of halogen substituents such as perchloro or perfluoroalkyls) independently selected from the group of substituents listed below in the definition for "substituted." "Halo-substituted alkyl" refers to an alkyl group substituted with one or more halogen atoms (e.g., fluoromethyl, difluoromethyl, trifluoromethyl, perfluoroethyl, and the like). The terms "partially or fully saturated carbocyclic ring" (also referred to as "partially or fully saturated cycloalkyl") refers to nonaromatic rings that are either partially or fully hydrogenated and may exist as a single ring, bicyclic ring or a spiral ring. Unless specified otherwise, the carbocyclic ring is generally a 3- to 8-membered ring (preferably, 3- to 6-membered ring). For example, partially or fully saturated carbocyclic rings (or cycloalkyl) include groups such as cyclopropyl, cyclopropenyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclpentenyl, cyclopentadienyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, norbornyl (bicyclo[2.2.1]heptyl), norbomenyl, bicyclo[2.2.2]octyl, and the like. When designated as being "optionally substituted", the partially saturated or fully saturated cycloalkyl group may be unsubstituted or substituted with one or more substituents (typically, one to three substituents) independently selected from the group of substituents listed below in the definition for "substituted." A substituted carbocyclic ring also includes groups wherein the carbocyclic ring is fused to a phenyl ring (e.g., indanyl). The carbocyclic group may be attached to the chemical entity or moiety by any one of the carbon atoms within the carbocyclic ring system. Similarly, any cycloalkyl portion of a group (e.g., cycloalkylalkyl, cycloalkylamino, etc.) has the same definition as above. The term "partially saturated or fully saturated heterocyclic ring" (also referred to as "partially saturated or fully saturated heterocycle") refers to nonaromatic rings that are either partially or fully hydrogenated and may exist as a single ring, bicyclic ring or a spiral ring. Unless specified otherwise, the heterocyclic ring is generally a 3- to 6-membered ring containing 1 to 3 heteroatoms (preferably 1 or 2 heteroatoms) independently selected from sulfur, oxygen or nitrogen. Partially saturated or fully saturated heterocyclic rings include groups such as epoxy, aziridinyl, tetrahydrofuranyl, dihydrofuranyl, dihydropyridinyl, pyrrolidinyl, N-methylpyrrolidinyl, imidazolidinyl, imidazolinyl, piperidinyl, piperazinyl, pyrazolidinyl, 2H-pyranyl, 4H-pyranyl, 2H-chromenyl, oxazinyl, morpholino, thiomorpholino, tetrahydrothienyl, tetrahydrothienyl 1 ,1-dioxide, and the like. Bicyclic rings include groups such as When indicated as being "optionally substituted", the partially saturated or fully saturated heterocycle group may be unsubstiuted or substituted with one or more substituents (typically, one to three substituents) independently selected from the group of substituents listed below in the definition for "substituted." A substituted heterocyclic ring includes groups wherein the heterocyclic ring is fused to an aryl or heteroaryl ring (e.g., 2,3-dihydrobenzofuranyl, 2,3-dihydroindolyl, 2,3-dihydrobenzothiophenyl, 2,3- dihydrobenzothiazolyl, etc.). The heterocyclic group may be attached to the chemical entity or moiety by any one of the ring atoms within the heterocyclic ring system. Similarly, any heterocycle portion of a group (e.g., heterocycle-substituted alkyl, heterocycle carbonyl, etc.) has the same definition as above. The term "aryl" or "aromatic carbocyclic ring" refers to aromatic moieties having a single (e.g., phenyl) or a fused ring system (e.g., naphthalene, anthracene, phenanthrene, etc.). A typical aryl group is a 6- to 10-membered aromatic carbocyclic ring(s). When indicated as being "optionally substituted", the aryl groups may be unsubstituted or substituted with one or more substituents (preferably no more than three substituents) independently selected from the group of substituents listed below in the definition for "substituted" (unless specified otherwise). Substituted aryl groups include a chain of aromatic moieties (e.g., biphenyl, terphenyl, phenylnaphthalyl, etc.). The aryl group may be attached to the chemical entity or moiety by any one of the carbon atoms within the aromatic ring system. Similarly, the aryl portion (i.e., aromatic moiety) of an aroyl or aroyloxy (i.e., (aryl)-C(O)-O-) has the same definition as above. The term "heteroaryl" or "heteroaromatic ring" refers to aromatic moieties containing at least one heteratom (e.g., oxygen, sulfur, nitrogen or combinations thereof) within a 5- to 10-membered aromatic ring system (e.g., pyrrolyl, pyridyl, pyrazolyl, indolyl, indazolyl, thienyl, furanyl, benzofuranyl, oxazolyl, imidazolyl, tetrazolyl, triazinyl, pyrimidyl, pyrazinyl, thiazolyl, purinyl, benzimidazolyl, quinolinyl, isoquinolinyl, benzothiophenyl, benzoxazolyl, etc.). The heteroaromatic moiety may consist of a single or fused ring system. A typical single heteroaryl ring is a 5- to 6-membered ring containing one to three heteroatoms independently selected from oxygen, sulfur and nitrogen and a typical fused heteroaryl ring system is a 9- to 10-membered ring system containing one to four heteroatoms independently selected from oxygen, sulfur and nitrogen. When indicated as being "optionally substituted", the heteroaryl groups may be unsubstituted or substituted with one or more substituents (preferably no more than three substituents) independently selected from the group of substituents listed below in the definition for "substituted" (unless specified otherwise). The heteroaryl group may be attached to the chemical entity or moiety by any one of the atoms within the aromatic ring system (e.g., imidazol-1-yl, imidazol-2-yl, imidazol-4-yl, imidazol-5-yl, pyrid-2-yl, pyrid-3-yl, pyrid-4-yl, pyrid-5-yl, or pyrid-6-yl). Similarly, the heteroaryl portion (i.e., heteroaromatic moiety) of a heteroaroyloxy (i.e., (heteroaryl)-C(O)-O-) has the same definition as above. The term "acyl" refers to alkyl, partially saturated or fully saturated cycloalkyl, partially saturated or fully saturated heterocycle, aryl, and heteroaryl substituted carbonyl groups. For example, acyl includes groups such as (CrC₆)alkanoyl (e.g., formyl, acetyl, propionyl, butyryl, valeryl, caproyl, t-butylacetyl, etc.), (C₃-C₆)cycloalkylcarbonyl (e.g., cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, etc.), heterocyclic carbonyl (e.g., pyrrolidinylcarbonyl, pyrrolid-2-one-5-carbonyl, piperidinylcarbonyl, piperazinylcarbonyl, tetrahydrofuranylcarbonyl, etc.), aroyl (e.g., benzoyl) and heteroaroyl (e.g., thiophenyl-2-carbonyl, thiophenyl-3-carbonyl, furanyl-2-carbonyl, furanyl-3-carbonyl, 1 H-pyrroyl-2-carbonyl, 1 H-pyrroyl-3-carbonyl, benzo[b]thiophenyl-2-carbonyl, etc.). In addition, the alkyl, cycloalkyl, heterocycle, aryl and heteroaryl portion of the acyl group may be any one of the groups described in the respective definitions above. When indicated as being "optionally substituted", the acyl group may be unsubstituted or optionally substituted with one or more substituents (typically, one to three substituents) independently selected from the group of substituents listed below in the definition for "substituted" or the alkyl, cycloalkyl, heterocycle, aryl and heteroaryl portion of the acyl group may be substituted as described above in the preferred and more preferred list of substituents, respectively. The term "substituted" specifically envisions and allows for one or more substitutions that are common in the art. However, it is generally understood by those skilled in the art that the substituents should be selected so as to not adversely affect the pharmacological characteristics of the compound or adversely interfere with the use of the medicament. Suitable substituents for any of the groups defined above include (C_rC₆)alkyl, (C₃-C₇)cycloalkyl, (C₂-C₆)alkenyl, (C_rC₆)alkylidenyl, aryl, heteroaryl, 3- to 6- membered heterocycle, halo (e.g., chloro, bromo, iodo and fluoro), cyano, hydroxy, (CrC₆)alkoxy, aryloxy, sulfhydryl (mercapto), (CVC^alkylthio, arylthio, amino, mono- or di-(C_rC₆)alkyl amino, quaternary ammonium salts, amino(C_rC₆)alkoxy, aminocarboxylate (i.e., (CrC₆)alkyl-O-C(O)-NH-), hydroxy(C₂- C₆)alkylamino, amino(C_rC₆)alkylthio, cyanoamino, nitro, (C_rC₆)carbamyl, keto (oxy), acyl, (Ci-C₆)alkyl- CO₂-, glycolyl, glycyl, hydrazino, guanyl, sulfamyl, sulfonyl, sulfinyl, thio(C₁-C₆)alkyl-C(O)-, thio(C_r C₆)alkyl-CO₂-, and combinations thereof. In the case of substituted combinations, such as "substituted aryl(C₁-C₆)alkyl", either the aryl or the alkyl group may be substituted, or both the aryl and the alkyl groups may be substituted with one or more substituents (typically, one to three substituents except in the case of perhalo substitutions). An aryl or heteroaryl substituted carbocyclic or heterocyclic group may be a fused ring (e.g., indanyl, dihydrobenzofuranyl, dihydroindolyl, etc.). The term "halo" refers to a chloro, bromo, fluoro or iodo group. The term "solvate" refers to a molecular complex of a compound represented by Formula (I) (including prodrugs and pharmaceutically acceptable salts thereof) with one or more solvent molecules. Such solvent molecules are those commonly used in the pharmaceutical art, which are known to be innocuous to the recipient, e.g., water, ethanol, and other Class 3 solvents (see, US Federal Drug Administration Guidelines for a list of Class 3 solvents). The term "hydrate" refers to the complex where the solvent molecule is water. The term "protecting group" or "Pg" refers to a substituent that is commonly employed to block or protect a particular functionality while reacting other functional groups on the compound. For example, an "amino-protecting group" is a substituent attached to an amino group that blocks or protects the amino functionality in the compound. Suitable amino-protecting groups include acetyl, trifluoroacetyl, t- butoxycarbonyl (BOC), benzyloxycarbonyl (CBz) and 9-fluorenylmethylenoxycarbonyl (Fmoc). For a general description of protecting groups and their use, see T. W. Greene, Protective Groups in Organic Synthesis, John Wiley & Sons, New York, 1991. The term "ligand" refers to a compound that binds to a receptor. As used herein, the ligand may possess partial or full agonist or antagonist activity. The term "agonist" unless indicated otherwise includes both partial and full agonists. Full agonists are preferred. The term "modulator" refers to a ligand that increases or decreases the action of an agonist by combining with a distinct site on the receptor macromolecule. The phrase "therapeutically effective amount" means an amount of a compound of the present invention that (i) treats or prevents the particular disease, condition, or disorder, (ii) attenuates, ameliorates, or eliminates one or more symptoms of the particular disease, condition, or disorder, or (iii) prevents or delays the onset of one or more symptoms of the particular disease, condition, or disorder described herein. The term "animal" refers to humans, companion animals (e.g., dogs, cats and horses), food-source animals, zoo animals, marine animals, birds and other similar animal species. "Edible animals" refers to food-source animals such as cows, pigs, sheep and poultry. The phrase "pharmaceutically acceptable" indicates that the substance or composition must be compatible chemically and/or toxicologically, with the other ingredients comprising a formulation, and/or the mammal being treated therewith. The terms "treating", "treat", or "treatment" embrace both preventative, i.e., prophylactic, and palliative treatment. The term "compound(s) of the present invention" (unless specifically identified otherwise) refers to compounds of Formula (I), prodrugs thereof, pharmaceutically acceptable salts of the compounds, and/or the prodrugs, and hydrates or solvates of the compounds, the salts, and/or the prodrugs, as well as, all stereoisomers (including diastereoisomers and enantiomers), tautomers and isotopically labeled compounds. DETAILED DESCRIPTION Compounds of the present invention may be synthesized by synthetic routes that include processes analogous to those known in the chemical arts, particularly in light of the description contained herein. The starting materials are generally available from commercial sources such as Aidrich Chemicals (Milwaukee, Wl) or are readily prepared using methods well known to those skilled in the art (e.g., prepared by methods generally described in Louis F. Fieser and Mary Fieser, Reagents for Organic Synthesis, v. 1-19, Wiley, New York (1967-1999 ed.), or Beilsteins Handbuch der organischen Chemie. 4. Aufl. ed. Springer-Verlag, Berlin, including supplements (also available via the Beilstein online database)). For illustrative purposes, the reaction scheme depicted below provides a potential route for synthesizing the compounds of the present invention as well as key intermediates. Those skilled in the art will appreciate that other synthetic routes may be used to synthesize the inventive compounds. Although specific starting materials and reagents are depicted in the scheme and discussed below, other starting materials and reagents can be easily substituted to provide a variety of intermediates and/or reaction conditions. In addition, many of the compounds prepared by the method described below can be further modified in light of this disclosure using conventional chemistry well known to those skilled in the art. In the preparation of compounds of the present invention, protection of remote functionality (e.g., secondary amine) of intermediates may be necessary. The need for such protection will vary depending on the nature of the remote functionality and the conditions of the preparation methods. Suitable amino- protecting groups (NH-Pg) include acetyl, trifluoroacetyl, f-butoxycarbonyl (BOC), benzyloxycarbonyl (CBz) and 9-fluorenylmethyleneoxycarbonyl (Fmoc). The need for such protection is readily determined by one skilled in the art. For a general description of protecting groups and their use, see T. W. Greene, Protective Groups in Organic Synthesis. John Wiley & Sons, New York, 1991. Scheme I illustrates the general procedures for preparing a compound of the present invention where R², R³, R⁴ and R⁵ are all hydrogen, and R⁹ is an aryl or heteroaryl group (e.g., compound of Formula (I-A)).

(l-A-1) Scheme I The allyl ether (1a) can be easily prepared by condensing an allyl halide (e.g., ally! bromide) with the desired alcohol. The allyl ether (1a) can then be rearranged to the corresponding allyl alcohol (1 b) by means of Claisen rearrangement reaction conditions (e.g, heating at an elevated temperature). Cyclization to the 2,3-dihydrofuran (1c) can be accomplished by treating the allyl alcohol (1b) with a peracid (e.g., m-chloroperbenzoic acid) followed by treatment with a base (e.g., alkali hydroxide). The alcohol functionality is protected with an alcohol protecting group (e.g., mesylate) and then the aryl or heteroaryl group (R⁹) is introduced via metal-mediated cross-coupling reactions such as the Suzuki reaction (See: A. Suzuki in Metal-Catalyzed Cross-Coupling Reactions: F. Diederich and PJ. Stang, Eds.; Wiiey-VCH Verlag, Weinheim, Germany, Chapter 2 (1998) and N. Miyaura and A. Suzuki Chem. Rev., 95, 2457-2483 (1995)) and the Stille reaction (T.N. Mitchell in Metal-Catalyzed Cross-Coupling Reactions: F. Diederich and P.J. Stang, Eds.; Wiley-VCH Verlag, Weinheim, Germany, Chapter 4 (1998)). In a preferred method, intermediate (1e) may be produced by Suzuki reaction of intermediate (1d) with a compound of Formula R⁹-B(OH)₂ in the presence of a complex or salt of palladium (e.g., Pd(PPh₃)₄, Pd(OAc)₂), a base (e.g., cesium carbonate, sodium carbonate, cesium fluoride, potassium phosphate), and a suitable solvent (e.g., toluene, water, dioxane, N,N-dimethylformamide (DMF), or dimethoxyethane (DME)) in the presence or absence of added ligand (e.g., dppf, dppb). Preferred reaction temperatures range from about 0 ⁰C to about 120 ⁰C. The amine (l-A-1) can be prepared by treating the mesylate (1e) with ammonium hydroxide in a suitable solvent (e.g., acetonitrile (ACN), dioxane, DMF, or N- methylprrolidone (NMP)) at about 25⁰C to about 120⁰C. Scheme Il illustrates the general procedures for preparing a compound of the present invention where R^1b is other than hydrogen (e.g., compound of Formula (l-A-2)).

Scheme Il Starting with the protected alcohol (1d) from the scheme above, an amine or protected amine functionality may be introduced prior to the Suzuki reaction by treating intermediate (1d) with the desired amine in the presence of a weak base (e.g., triethylamine or potassium carbonate). After the introduction of the R⁹ functionality using the procedures described above in Scheme I₁ any remaining protecting groups may then be removed using conventional methods well-known to those skilled in the art to produce the compound of Formula (l-A-2). Numerous amine compounds of Formula R^1aR^1bNH are available from commercial sources or prepared by known methods readily available to those skilled in the art. Scheme III illustrates the general procedures for preparing a compound of the present invention where R⁷ is an aryl or heteroaryl group (e.g., compound of Formula (I-B)).

(I-B) (3c) Scheme III A bromo group may be introduced in the 5-position using a conventional bromination agent (e.g., N-bromosuccinimide (NBS)). The aryl or heteroaryl group (R⁷) can then be introduced via a metal- mediated cross-coupling reaction such as the Suzuki reaction described above in Scheme I. The amino- protecting group may be removed using standard procedures well-known to those skilled in the art. For example, a BOC-protected intermediate (3b) can be treated with trifluoroacetic acid in an aprotic solvent (e.g., methylene chloride). The halo group on the aryl ring may then be removed by hydrogenation (e.g., Pd/C catalyzed hydrogenation) to produce the compound of Formula (I-B). Scheme IV illustrates the general procedures for preparing a compound of the present invention where R⁹ is an aryl or heteroaryl group (e.g., compound of Formula (1-C)).

The bromo group may be introduced at the 7 position using standard bromination procedures (e.g., N-bromosuccinimide). The alcohol functionality is protected with an alcohol protecting group (e.g., mesylate) and then the aryl or heteroaryl group (R⁹) is introduced via metal-mediated cross-coupling reactions such as the Suzuki reaction described above in Scheme I to produce intermediate (4c). The amino group can then be introduced by treating the mesylate (4c) with the desired amine (R^1aR^1bNH). Scheme V illustrates the general procedures for preparing a compound of the present invention where n is 2 (e.g., compound of Formula (I-D)).

(I-D) Scheme V The mesylate intermediate (1e) can be converted to the corresponding cyano intermediate (5a) using traditional substitution with a cyanide. For example, intermediate (1e) is reacted with an alkali metal cyanide (e.g., NaCN) in the presence of an appropriate solvent. The cyano group may then be reduced to the primary amine to produce a compound of Formula (I-D). For example, the cyano group may be reduced with a hydroborane (e.g., BH₃S(CH₃)₂). The primary amino group may be further derivatized by alkylation to the secondary or tertiary amine using standard procedures well-known to those skilled in the art.

(I-E) Scheme Vl Intermediate alcohol (1c) may be oxidized to its corresponding aldehyde (6a) using standard procedures well-known to those skilled in the art. For example, alcohol (1c) may be treated with oxalyl chloride to produce the carbaldehyde (6a). The R² group may then be introduced into the compound using a standard Grignard reagent (e.g., R²MgBr). The alcohol is then converted to a leaving group. For example, the alcohol is treated with mesylate chloride to form the mesylate (6c). The compound of Formula (I-E) is then produced by reacting the mesylate (6c) with the desired amine (R^1aR^1bNH). Conventional methods and/or techniques of separation and purification known to one of ordinary skill in the art can be used to isolate the compounds of the present invention, as well as the various intermediates related thereto. Such techniques will be well-known to one of ordinary skill in the art and may include, for example, all types of chromatography (high pressure liquid chromatography (HPLC), column chromatography using common adsorbents such as silica gel, and thin-layer chromatography), recrystallization, and differential (i.e., liquid-liquid) extraction techniques. The term "salts" refers to inorganic and organic salts of a compound of the present invention. These salts can be prepared in situ during the final isolation and purification of a compound, or by separately reacting the compound, or prodrug with a suitable organic or inorganic acid and isolating the salt thus formed. Representative salts include the hydrobromide, hydrochloride, hydroiodide, sulfate, bisulfate, nitrate, acetate, trifluoroacetate, oxalate, besylate, palmitiate, pamoate, malonate, stearate, laurate, malate, borate, benzoate, lactate, phosphate, hexafluorophosphate, benzene sulfonate, tosylate, formate, citrate, maleate, fumarate, succinate, tartrate, naphthylate, mesylate, glucoheptonate, lactobionate, and laurylsulphonate salts, and the like. See, e.g., Berge, et al., J. Pharm. Sci., 66, 1-19 (1977). The compounds of the present invention may exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanoi, and the like, and it is intended that the invention embrace both solvated and unsolvated forms. Suitable pharmaceutically acceptable solvents include the Class 3 solvents listed in the United States Federal Drug Administration Guidelines. The term "prodrug" means a compound that is transformed in vivo to yield a compound of Formula (I), a pharmaceutically acceptable salt of the compound, or a hydrate or solvate of the compound or salt. The transformation may occur by various mechanisms, such as through hydrolysis in blood. A discussion of the use of prodrugs is provided by T. Higuchi and W. Stella, "Pro-drugs as Novel Delivery Systems," Vol. 14 of the A.C.S. Symposium Series, and in Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987. For example, a prodrug could be formed by replacing the hydrogen atom in the amine group with a group such as an alkyl group, R-carbonyl, RO-carbonyl, NRR'-carbonyl where R and R' are each independently (CrC₁₀)alkyl, (C₃-C₇)cycloalkyl, benzyl, or R-carbonyl is a natural α-aminoacyl or natural α- aminoacyl-natural α-aminoacyl, -C(OH)C(O)OY' wherein Y' is H, (C_rC₆)alkyl or benzyl, -C(OY₀)Yi wherein Y₀ is (C₁-C₄) alkyl and Y₁ is (CrC₆)alkyl, carboxy(C_rC₆)alkyl, amino(C_rC₄)alkyl or mono-N- or di- N,N-(CrC₆)alkylaminoalkyl, -C(Y₂)Ys wherein Y₂ is H or methyl and Y₃ is mono-N- or di-N, N-(C₁- C₆)alkylamino, morpholino, piperidin-1-yl or pyrrolidin-1-yl. The present invention also embraces isotopically-labeled compounds of the present invention which are identical to those recited herein, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes that can be incorporated into compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, fluorine and chlorine, such as ²H, ³H, ¹³C, ¹⁴C, ¹⁵N, ¹⁸O, ¹⁷0, ¹⁸F, and ³⁶CI, respectively. Certain isotopically-labeled compounds of the present invention (e.g., those labeled with ³H and ¹⁴C) are useful in compound and/or substrate tissue distribution assays. Tritiated (i.e., ³H) and carbon-14 (i.e., ¹⁴C) isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavier isotopes such as deuterium (i.e., ²H) may afford certain therapeutic advantages resulting from greater metabolic stability (e.g., increased in vivo half-life or reduced dosage requirements) and hence may be preferred in some circumstances, lsotopically labeled compounds of the present invention can generally be prepared by following procedures analogous to those disclosed in the Schemes and/or in the Examples hereinbelow, by substituting an isotopically labeled reagent for a non- isotopically labeled reagent. Compounds of the present invention are useful 5-HT₂₀ agonists and/or 5-HT_2a antagonists; therefore, another embodiment of the present invention is a pharmaceutical composition comprising a therapeutically effective amount of a compound of the present invention and a pharmaceutically acceptable excipient, diluent or carrier. A typical formulation is prepared by mixing a compound of the present invention and a carrier, diluent or excipient. Suitable carriers, diluents and excipients are well known to those skilled in the art and include materials such as carbohydrates, waxes, water soluble and/or swellable polymers, hydrophilic or hydrophobic materials, gelatin, oils, solvents, water, and the like. The particular carrier, diluent or excipient used will depend upon the means and purpose for which the compound of the present invention is being applied. Solvents are generally selected based on solvents recognized by persons skilled in the art as safe (GRAS) to be administered to a mammal. In general, safe solvents are non-toxic aqueous solvents such as water and other non-toxic solvents that are soluble or miscible in water. Suitable aqueous solvents include water, ethanol, propylene glycol, polyethylene glycols (e.g., PEG400, PEG300), etc. and mixtures thereof. The formulations may also include one or more buffers, stabilizing agents, surfactants, wetting agents, lubricating agents, emulsifiers, suspending agents, preservatives, antioxidants, opaquing agents, glidants, processing aids, colorants, sweeteners, perfuming agents, flavoring agents and other known additives to provide an elegant presentation of the drug (i.e., a compound of the present invention or pharmaceutical composition thereof) or aid in the manufacturing of the pharmaceutical product (i.e., medicament). The formulations may be prepared using conventional dissolution and mixing procedures. For example, the bulk drug substance (i.e., compound of the present invention or stabilized form of the compound (e.g., complex with a cyclodextrin derivative or other known complexation agent)) is dissolved in a suitable solvent in the presence of one or more of the excipients described above. The compound of the present invention is typically formulated into pharmaceutical dosage forms to provide an easily controllable dosage of the drug and to give the patient an elegant and easily handleable product. The pharmaceutical composition (or formulation) for application may be packaged in a variety of ways depending upon the method used for administering the drug. Generally, an article for distribution includes a container having deposited therein the pharmaceutical formulation in an appropriate form. Suitable containers are well-known to those skilled in the art and include materials such as bottles (plastic and glass), sachets, ampoules, plastic bags, metal cylinders, and the like. The container may also include a tamper-proof assemblage to prevent indiscreet access to the contents of the package. In addition, the container has deposited thereon a label that describes the contents of the container. The label may also include appropriate warnings.. The present invention further provides methods of treating 5-HT₂ receptor-mediated diseases, conditions, or disorders in an animal in need of such treatment that include administering to the animal (preferably, a human) a therapeutically effective amount of a compound of the present invention or a pharmaceutical composition comprising an effective amount of a compound of the present invention and a pharmaceutically acceptable excipient, diluent, or carrier. The method is particularly useful for treating 5- HT₂₀ receptor-mediated diseases, conditions, or disorders. In particular, the compounds of the present invention act as potent full agonists at the 5-HT₂₀ receptor, and as antagonists or very weak partial agonists at the 5-HT_2a and 5-HT_2b receptors. The compounds of the present invention are functionally selective for 5-HT_2c against 5-HT_2a and 5-HT_2b, by virtue of their much higher agonistic potency (lower EC₅₀) for 5-HT₂₀ than that observed for 5-HT_2a and/or 5-HT_2b or their lack of agonistic activity at 5-HT_2a and/or 5-HT_2b. Receptor binding data or binding selectivity data may not always correlate with or reflect functional data or functional selectivity data. For example, a compound may be selective for the 5-HT₂₀ receptor when functional assays are analyzed, but in the binding assays the compound may have the same potency at other 5-HT receptors. Thus, the term "selective" as used herein in relation to the present invention with respect to methods of treatment means "functionally selective". Diseases, conditions, and/or disorders modulated by 5HT₂ receptor ligands include eating disorders (e.g., binge eating disorder, anorexia, and bulimia), weight loss or control (e.g., reduction in calorie or food intake, and/or appetite suppression), obesity, depression, atypical depression, bipolar disorders, psychoses, schizophrenia, behavioral addictions, suppression of reward-related behaviors (e.g., conditioned place avoidance, such as suppression of cocaine- and morphine-induced conditioned place preference), substance abuse, addictive disorders, impulsivity, alcoholism (e.g., alcohol abuse, addiction and/or dependence including treatment for abstinence, craving reduction and relapse prevention of alcohol intake), tobacco abuse (e.g., smoking addiction, cessation and/or dependence including treatment for craving reduction and relapse prevention of tobacco smoking), premenstrual syndrome or late luteal phase syndrome, migraine, panic disorder, anxiety, post-traumatic syndrome, dementia (including memory loss, Alzheimer's disease, dementia of aging, vascular dementia, mild cognitive impairment, age-related cognitive decline, and mild neurocognitive disorder), seizure disorders, epilepsy, gastrointestinal disorders (e.g., dysfunction of gastrointestinal motility or intestinal propulsion), attention deficit disorders or attention hyperactivity disorders (ADD/ADHD), disruptive behavior disorders, impulse control disorders, borderline personality disorder, obsessive compulsive disorder, chronic fatigue syndrome, anorexia nervosa, disorders of sleep (e.g., sleep apnea), autism, epilepsy, mutism, spinal cord injury, damage of the central nervous system (e.g., trauma, stroke, neurodegenerative diseases or toxic or infective CNS diseases (e.g., encephalitis or meningitis)), cardiovascular disorders (e.g., thrombosis), Parkinson's disease, diabetes insipidus, and type Il diabetes. Accordingly, the compounds of the present invention described herein are useful in treating 5-HT₂ receptor-mediated diseases, conditions, or disorders. Consequently, the compounds of the present invention (including the compositions and processes used therein) may be used in the manufacture of a medicament for the therapeutic applications described herein. The compounds of the present invention can be administered to a patient at dosage levels in the range of from about 0.1 mg to about 1 ,000 mg per day (preferably, about 1 mg to about 500 mg per day, more preferably, about 25 mg to about 250 mg per day, most preferably about 5 mg to about 100 mg per day). For a normal adult human having a body weight of about 70 kg, a dosage in the range of from about 0.01 mg to about 20 mg per kilogram body weight is typically sufficient. However, some variability in the general dosage range may be required depending upon the age and weight of the subject being treated, the intended route of administration, the particular compound being administered and the like. The determination of dosage ranges and optimal dosages for a particular patient is well within the ability of one of ordinary skill in the art having the benefit of the instant disclosure. It is also noted that the compounds of the present invention can be used in sustained release, controlled release, and delayed release formulations, which forms are also well known to one of ordinary skill in the art. The compounds of this invention may also be used in conjunction with other pharmaceutical agents for the treatment of the diseases/conditions described herein. Therefore, methods of treatment that include administering compounds of the present invention in combination with other pharmaceutical agents are also provided. Suitable pharmaceutical agents that may be used in combination with the compounds of the present invention include anti-obesity agents such as apolipoprotein-B secretion/microsomal triglyceride transfer protein (apo-B/MTP) inhibitors, 11β-hydroxy steroid dehydrogenase-1 (11 β-HSD type 1) inhibitors, PYY_3-36 and analogs thereof, MCR-4 agonists, cholecystokinin-A (CCK-A) agonists, monoamine reuptake inhibitors (such as sibutramine), sympathomimetic agents, β₃ adrenergic receptor agonists, dopamine agonists (such as bromocriptine), melanocyte-stimulating hormone receptor analogs, cannabinoid 1 receptor antagonists (e.g., rimonabant), melanin concentrating hormone antagonists, leptins (the OB protein), leptin analogs, leptin receptor agonists, galanin antagonists, lipase inhibitors (such as tetrahydrolipstatin, i.e. orlistat), anorectic agents (such as a bombesin agonist), Neuropeptide-Y receptor antagonists (e.g., NPY Y5 receptor antagonists, such as the spiro compounds described in US Patent Nos. 6,566,367; 6,649,624; 6,638,942; 6,605,720; 6,495,559; 6,462,053; 6,388,077; 6,335,345; and 6,326,375; US Publication Nos. 2002/0151456 and 2003/036652; and PCT Publication Nos. WO 03/010175. WO 03/082190 and WO 02/048152), thyromimetic agents, dehydroepiandrosterone or an analog thereof, glucocorticoid receptor agonists or antagonists, orexin receptor antagonists, urocortin binding protein antagonists, glucagon-like peptide-1 receptor agonists, ciliary neurotrophic factors (such as Axokine™ available from Regeneron Pharmaceuticals, Inc., Tarrytown, NY and Procter & Gamble Company, Cincinnati, OH), human agouti- related proteins (AGRP), ghrelin receptor antagonists, histamine 3 receptor antagonists or inverse agonists, and neuromedin U receptor agonists. Other anti-obesity agents, including the preferred agents set forth hereinbelow, are well known, or will be readily apparent in light of the instant disclosure, to one of ordinary skill in the art. Especially preferred are anti-obesity agents selected from the group consisting of orlistat, sibutramine, bromocriptine, ephedrine, leptin, rimonabant, pseudoephedrine, PYY_3-36Or an analog thereof, and 2-oxo-N-(5-phenylpyrazinyl)spiro-[isobenzofuran-1 (3H),4'-piperidine]-1 '-carboxamide. Preferably, compounds of the present invention and combination therapies are administered in conjunction with exercise and a sensible diet.

Representative anti-obesity agents for use in the combinations, pharmaceutical compositions, and methods of the invention can be prepared using methods known to one of ordinary skill in the art, for example, sibutramine can be prepared as described in U.S. Pat. No. 4,929,629; bromocriptine can be prepared as described in U.S. Pat. Nos. 3,752,814 and 3,752,888; orlistat can be prepared as described in U.S. Pat. Nos. 5,274,143; 5,420,305; 5,540,917; and 5,643,874; rimonabant can be prepared as described in U.S. Pat. No. 5,624,941 ; PYY_3-36 (including analogs thereof) can be prepared as described in US Publication No. 2002/0141985 and WO 03/027637; and the NPY Y5 receptor antagonist 2-oxo-N-(5- phenylpyrazinyl)spiro[isobenzofuran-1(3H),4'-piperidine]-1'-carboxamide can be prepared as described in US Publication No. 2002/0151456. Other NPY Y5 receptor antagonists described in PCT Publication No. 03/082190 that may be useful in combination with a compound of the present invention are selected from the group consisting of: 3-oxo-N-(5-phenyl-2-pyrazinyl)-spiro[isobenzofuran-1 (3H), 4'-piperidine]-1'- carboxamide; 3-oxo-N-(7-trifluoromethylpyrido[3,2-b]pyridin-2-yl)-spiro-[isobenzofuran-1 (3H), 4'- piperidine]-1'-carboxamide; N- [5-(3-fluorophenyl)-2-pyrimidinyl]-3-oxospiro-[isobenzofuran-1(3H), [4¹- piperidine]-1'-carboxamide; frans-3'-oxo-N-(5-phenyl-2-pyrimidinyl)] spiro[cyclohexane-1 ,1'(3'H)- isobenzofuran]-4-carboxamide; frans-3'-oxo-N- [1-(3-quinolyl)-4-imidazolyl]spiro[cyclohexane-1 ,1'(3'H)- isobenzofuran]-4-carboxamide; frans-3-oxo-N-(5-phenyl-2-pyrazinyl)spiro[4-azaiso-benzof uran-1 (3H), 1'- cyclohexane]-4'-carboxamide; frans-N-[5-(3-fluorophenyl)-2-pyrimidinyl]-3-oxospiro[5-azaisobenzofuran- 1 (3H), 1 '-cyclohexane]-4'-carboxamide; frans-N-[5-(2-fluorophenyl)-2-pyrimidinyl]-3-oxospiro[5- azaisobenzof uran-1 (3H), 1 '-cyclohexane]-4'-carboxamide; frans-N-[1 -(3,5-difluorophenyl)-4-imidazolyl]-3- oxospiro[7-azaisobenzof uran-1 (3H), 1'-cyclohexane]-4'-carboxamide; frans-3-oxo-N-(1-phenyl-4- pyrazolyl)spiro[4-azaisobenzof uran-1 (3H), 1'-cyclohexane]-4'-carboxamide; frans-N-[1-(2-fluorophenyl)-3- pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide; frans-3-oxo-N-(l- phenyl-3-pyrazolyl)spiro[6-azaisobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide; frans-3-oxo-N-(2- phenyl-I ^.S-triazoM-yOspirote-azaisobenzofuran-I^H^I'-cyclohexaneH'-carboxamide; and pharmaceutically acceptable salts and esters thereof. All of the above recited U.S. patents and publications are incorporated herein by reference.

Other suitable pharmaceutical agents that may be administered in combination with the compounds of the present invention include agents designed to treat tobacco abuse (e.g., nicotine receptor partial agonists, bupropion hypochloride (also known under the tradename Zyban™) and nicotine replacement therapies), ADD/ADHD agents (e.g., Ritalin™, Strattera™, Concerta™ and Adderall™), and agents to treat alcoholism, such as opioid antagonists (e.g., naltrexone (also known under the tradename ReVia™) and nalmefene), disulfiram (also known under the tradename Antabuse™), and acamprosate (also known under the tradename Campral™)). In addition, agents for reducing alcohol withdrawal symptoms may also be co-administered, such as benzodiazepines, beta-blockers, clonidine, carbamazepine, pregabalin, and gabapentin (Neurontin™). Treatment for alcoholism is preferably administered in combination with behavioral therapy including such components as motivational enhancement therapy, cognitive behavioral therapy, and referral to self-help groups, including Alcohol Anonymous (AA). In addition to Zyban, other useful nicotine receptor partial agonists are described in US Patent Nos. 6,235,734; 6,410,550; and 6,462,035; all of which are incorporated herein by reference. Other pharmaceutical agents that may be used in combination include anti-inflammatory agents (e.g., COX-2 inhibitors); antihypertensive agents; antidepressants (e.g., fluoxetine hydrochloride (Prozac™)); cognitive improvement agents (e.g., donepezil hydrochloride (Aircept™) and other acetylcholinesterase inhibitors); neuroprotective agents (e.g., memantine); insulin and insulin analogs (e.g., LysPro insulin); GLP-1 (7-37) (insulinotropin) and GLP-1 (7-36)-NH₂; sulfonylureas and analogs thereof: chlorpropamide, glibenclamide, tolbutamide, tolazamide, acetohexamide, Glypizide^®, glimepiride, repaglinide, meglitinide; biguanides: metformin, phenformin, buformin; °=2-antagonists and imidazolines: midaglizole, isaglidole, deriglidole, idazoxan, efaroxan, fluparoxan; other insulin secretagogues: linogliride, A-4166; glitazones: ciglitazone, Actos^® (pioglitazone), englitazone, troglitazone, darglitazone, Avandia^® (BRL49653); fatty acid oxidation inhibitors: clomoxir, etomoxir; oc-glucosidase inhibitors: acarbose, miglitol, emiglitate, voglibose, MDL-25,637, camiglibose, MDL-73,945; β-agonists: BRL 35135, BRL 37344, RO 16-8714, ICI D7114, CL 316,243; phosphodiesterase inhibitors: L-386,398; lipid-lowering agents: benfluorex: fenfluramine; vanadate and vanadium complexes (e.g., Naglivan^®) and peroxovanadium complexes; amylin antagonists; glucagon antagonists; gluconeogenesis inhibitors; somatostatin analogs; antilipolytic agents: nicotinic acid, acipimox, WAG 994, pramlintide (Symlin™), AC 2993, nateglinide, aldose reductase inhibitors (e.g., zopolrestat), glycogen phosphorylase inhibitors, sorbitol dehydrogenase inhibitors, sodium-hydrogen exchanger type 1 (NHE-1) inhibitors and/or cholesterol biosynthesis inhibitors or cholesterol absorption inhibitors, especially a HMG-CoA reductase inhibitor, or a HMG-CoA synthase inhibitor, or a HMG-CoA reductase or synthase gene expression inhibitor, a CETP inhibitor, a bile acid sequesterant, a fibrate, an ACAT inhibitor, a squalene synthetase inhibitor, an anti-oxidant or niacin. The compounds of the present invention may also be administered in combination with a naturally occurring compound that acts to lower plasma cholesterol levels. Such naturally occurring compounds are commonly called nutraceuticals and include, for example, garlic extract, Hoodia plant extracts, and niacin. The compounds of the present invention have also been shown to be potent 5-HT_2a antagonists in vivo. Consequently, the compounds of the present invention may be used to treat psychotic disorders of the schizophrenic types, and in particular the compounds would be useful for removing or ameliorating such symptoms as anxiety, agitation, excessive aggression, tension, and social or emotional withdrawal in psychotic patients. In addition, the compounds may also be useful in the blocking of serotonin-induced contractions of bronchial tissues and of blood vessels, arteries as well as veins. The compounds of the present invention may also be useful as sedating-, anxiolytic-, anti-agressive-, anti-stress-, muscular protectant- and cardiovascular protectant agents and, consequently, they would be useful to protect warm-blooded animals, for example, in stress situations, e.g., during transport periods and the like situations. Additionally, the compounds of the present invention may be useful as protectors of endotoxine shocks and as antidiarrhoeals. Suitable antipsychotic agents (or neuroleptic agents) which may be used in combination with the compounds of the present invention include ziprasidone (e.g., GEODON®), risperidone (e.g., RISPERDAL®), olanzapine (e.g., ZYPREXA®), quetiapine (e.g., SEROQUEL®), clozapine (e.g., CLOZARIL®), haloperidol (e.g., HALDOL®) and pharmaceutically acceptable salts thereof. Ziprasidone (5-(2-(4-(1 ,2-benzisothiazol-3-yl)-piperazinyl)ethyl)-6-chloro-1 , 3-dihydro-2H-indol-2-one hydrochloride) may be purchased or prepared using the methods described in U.S. Patent Nos. 4,831 ,031 ; 5,312,925; and 6,150,366. Risperidone (3-[2-[4-(6-fluoro-1 ,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8, 9- tetrahydro-2-methyl-4H-pyrido[1 ,2-a]pyrimidin-4-one) may be purchased or prepared using the methods described in U.S. Patent Nos. 4,804,663; 5,453,425; and 5,616,587. Olanzapine (2-Methyl-10-(4-methyl- 1-piperazinyl)-4H-thieno-[2,3-b][1 ,5]benzodiazepine) may be purchased or prepared using the procedures described in U.S. Patent No. 5,229,382. Quetiapine (11-[4-[2-(2-Hydroxyethoxy)ethyl]-1- piperazinyl]dibenzo[b,f][1 ,4 ]thiazepine) may be purchased or prepared using the procedures described in U.S. Patent No. 4,879,288. In another embodiment of the present invention, the compounds of the present invention may be used in the treatment of sexual dysfunction. Sexual dysfunction (SD) is a significant clinical problem, which can affect both males and females. The causes of SD may be both organic as well as psychological. Organic aspects of SD are typically caused by underlying vascular diseases, such as those associated with hypertension or diabetes mellitus, by prescription medication and/or by psychiatric disease such as depression. Physiological factors include fear, performance anxiety and interpersonal conflict. SD impairs sexual performance, diminishes self-esteem and disrupts personal relationships thereby inducing personal distress. In the clinic, SD disorders have been divided into female sexual dysfunction (FSD) disorders and male sexual dysfunction (MSD) disorders (Melman et al 1999). FSD is best defined as the difficulty or inability of a woman to find satisfaction in sexual expression. Male sexual dysfunction (MSD) is generally associated with erectile dysfunction, also known as male erectile dysfunction (MED) (Benet et al 1994 - Male Erectile dysfunction assessment and treatment options. Comp. Ther. 20: 669-673.). The compounds of the invention are particularly beneficial for the prophylaxis and/or treatment of sexual dysfunction in the male (e.g. male erectile dysfunction - MED) and in the female - female sexual dysfunction (FSD), e.g. female sexual arousal disorder (FSAD). It is known that some individuals can suffer from male erectile dysfunction (MED). MED is defined as: "the inability to achieve and/or maintain a penile erection for satisfactory sexual performance" (NIH Consensus Development Panel on Impotence, 1993)" The categories of female sexual dysfunction (FSD) are best defined by contrasting them to the phases of normal female sexual response: desire, arousal and orgasm (see S R Leiblum, (1998), Definition and Classification of Female Sexual Disorders, Int. J. Impotence Res.. 10, S104-S106). Desire or libido is the drive for sexual expression. Its manifestations often include sexual thoughts either when in the company of an interested partner or when exposed to other erotic stimuli. Arousal includes the vascular response to sexual stimulation, an important component of which is genital engorgement and increased vaginal lubrication, elongation of the vagina and increased genital sensation/sensitivity and a subjective excitement response. Orgasm is the release of sexual tension that has culminated during arousal. Hence, FSD occurs when a woman has an absent, inadequate or unsatisfactory response in any one or more of these phases, usually desire, arousal or orgasm. The American Psychiatric Association classifies female sexual dysfunction (FSD) into four classes: FSAD, hypoactive sexual desire disorder (HSDD), female orgasmic disorder (FOD), and sexual pain disorders (e.g. dyspareunia and vaginismus) [see the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV)]. DSM-IV defines the four classes as follows: HSDD - Persistently or recurrently deficient (or absent) sexual fantasies and desire for sexual activity. The judgment of deficiency or absence is made by the clinician, taking into account factors that affect functioning, such as age and the context of the persons life. FSAD - Persistent or recurrent inability to attain, or to maintain until completion of the sexual activity, an adequate lubrication-swelling response of sexual excitement. FOD - Persistent or recurrent delay in, or absence of, orgasm following a normal sexual excitement phase. Women exhibit wide variability in the type or intensity of stimulation that triggers orgasm. The diagnosis of FOD should be based on the clinician's judgment that the woman's orgasmic capacity is less than would be reasonable for her age, sexual experience, and the adequacy of the sexual stimulation she receives. Sexual Pain Disorders such as Dyspareunia and Vaginismus. Dysparenuia - Recurrent or persistent genital pain associated with sexual intercourse. Vaginismus - Recurrent or persistent involuntary spasm of the musculature of the outer third of the vagina that interferes with sexual intercourse. HSDD is present if a woman has no or little desire to be sexual, and has no or few sexual thoughts or fantasies. This type of FSD can be caused by low testosterone levels, due either to natural menopause or to surgical menopause. Other causes in both pre-menopausal woman (i.e. woman who are pre-menopausal and who have not have hysterectomies) as well as post-menopausal women include illness, medications, fatigue, depression and/or anxiety. Factors having a potential (conscious or sub¬ conscious) psychological impact such as relationship difficulties or religious factors may be related to the presence of/development of HSDD in females. The Diagnostic and Statistical Manual (DSM) IV of the American Psychiatric Association defines Female Sexual Arousal Disorder (FSAD) as being: "... a persistent or recurrent inability to attain or to maintain until completion of the sexual activity adequate lubrication-swelling response of sexual excitement. The disturbance must cause marked distress or interpersonal difficulty. ...". The arousal response consists of vasocongestion in the pelvis, vaginal lubrication and expansion and swelling of the external genitalia. The disturbance causes marked distress and/or interpersonal difficulty. FSAD is a highly prevalent sexual disorder affecting pre-, peri- and post-menopausal (± hormone replacement therapy (HRT)) women. It is associated with concomitant disorders such as depression, cardiovascular diseases, diabetes and urogenital (UG) disorders. The primary consequences of FSAD are lack of engorgement/swelling, lack of lubrication and lack of pleasurable genital sensation. The secondary consequences of FSAD are reduced sexual desire, pain during intercourse and difficulty in achieving an orgasm. It has recently been hypothesized that there is a vascular basis for at least a proportion of patients with symptoms of FSAD (Goldstein et al., Int. J. Impot. Res.. 10, S84-S90.1998) with animal data supporting this view (Park et al., Int. J. Impot. Res., 9, 27-37, 1997). Drug candidates for treating FSAD, which are under investigation for efficacy, are primarily erectile dysfunction therapies that promote circulation to male genitalia. They consist of two types of formulation, oral or sublingual medications (Apomorphine, Phentolamine, phosphodiesterase type 5 (PDE5) inhibitors, e.g. Sildenafil), and prostaglandin (PGE₁) that are injected or administered transurethrally in men and topically to the genitalia in women. The compounds of the present invention are advantageous by providing a means for restoring a normal sexual arousal response - namely increased genital blood flow leading to vaginal, clitoral and labial engorgement. This will result in increased vaginal lubrication via plasma transudation, increased vaginal compliance and increased genital sensitivity. Hence, the present invention provides a means to restore, or potentiate, the normal sexual arousal response. By female genitalia herein we mean: "The genital organs consist of an internal and external group. The internal organs are situated within the pelvis and consist of ovaries, the uterine tubes, uterus and the vagina. The external organs are superficial to the urogenital diaphragm and below the pelvic arch. They comprise the mons pubis, the labia majora and minora pudendi, the clitoris, the vestibule, the bulb of the vestibule, and the greater vestibular glands" (Gray's Anatomy, CD. Clemente, 13^th American Edition). RJ. Levin teaches us that because "... male and female genitalia develop embryologically from the common tissue anlagen, [that] male and female genital structures are argued to be homologues of one another. Thus the clitoris is the penile homologue and the labia homologues of the scrotal sac. ..." (Levin, R.J. (1991 ), EXP. Clin. Endocrinol.. 98, 61-69). In summary, FSAD is characterized by inadequate genital response to sexual stimulation. The genitalia do not undergo the engorgement that characterizes normal sexual arousal. The vaginal walls are poorly lubricated, so that intercourse is painful. Orgasms may be impeded. Arousal disorder can be caused by reduced oestrogen at menopause or after childbirth and during lactation, as well as by illnesses, with vascular components such as diabetes and atherosclerosis. Other causes result from treatment with diuretics, antihistamines, antidepressants e.g. selective serotonin reuptake inhibitors (SSRIs) or antihypertensive agents. FOD is the persistent or recurrent difficulty, delay in or absence of attaining orgasm following sufficient sexual stimulation and arousal, which causes personal distress. Sexual pain disorders (includes dyspareunia and vaginismus) are characterized by pain resulting from penetration and sexual activity and may be caused by medications which reduce lubrication, endometriosis, pelvic inflammatory disease, inflammatory bowel disease or urinary tract problems. According to a further aspect, the present invention additionally provides a method for the treatment and/or prevention of male sexual dysfunction (MSD), in particular male erectile dysfunction (MED) via treatment with a compound of the present invention as detailed hereinbefore. According to a yet further aspect, the present invention additionally provides a method for the treatment and/or prevention of male sexual dysfunction via treatment with a combination of a compound of the present invention and at least one additional pharmaceutical agent. Preferred additional pharmaceutical agents used in treating male sexual dysfunction (e.g., male erectile dysfunction) include: (1) one or more dopaminergic agents (e.g. D2, D3 or D4 agonists and apomorphine); (2) one or more of an NPY (neuropeptide Y) (preferably an NPY-1 and/or NPY-5 inhibitor); (3) one or more of a melanocortin receptor agonist or modulator or melanocortin enhancer; (4) one or more of an NEP inhibitor; (5) one or more of a PDE inhibitor (preferably, a cGMP PDE-5 inhibitor); and (6) one or more of a bombesin receptor antagonist or modulator. Men who display an insufficient response or lack of response to treatment with Viagra™ may benefit either from therapy based on treatment with compounds of the present invention alone or via combination therapy based on compound(s) of the present invention and a cGMP PDE5i, such as for example sildenafil. Patients with mild to moderate MED should benefit from combined treatment based on compound(s) of the present invention alone or in combination with a NEPi, and patients with severe MED may also respond. Mild, moderate and severe MED will be terms known to the man skilled in the art, but guidance can be found in: The Journal of Urology, vol 151 , 54-61 (Jan 1994). MED patient groups, which are described in more detail in Clinical Andrology vol 23,no.4, p773- 782, and chapter 3 of the book by I. Eardley and K. Sethia "Erectile Dysfunction - Current Investigation and Management, published by Mosby-Wolfe, are as follows: psyhcogenic, endocrinologic, neurogenic, arteriogenic, drug-induced sexual dysfunction (lactogenic) and sexual dysfunction related to cavernosal factors, particularly venogenic causes. Suitable cGMP PDE5 inhibitors for the use in combination with a compound of the present invention for the treatment of MED according to the present invention include: the pyrazolo [4,3- d]pyrimidin-7-ones disclosed in EP-A-0463756; the pyrazolo [4,3-d]pyrimidin-7-ones disclosed in published international application WO 01/27112; the pyrazolo [4,3-d]pyrimidin-7-ones disclosed in published international application WO 01/27113; the indole-1 ,4-diones disclosed in WO95/19978 and the triazin-4-ones disclosed in published international application WO99/24433. More preferred are compounds such as, 5-[2-ethoxy-5-(4-methyl-1-piperazinylsulphonyl)phenyl]- 1-methyl-3-n-propyl-1 ,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (sildenafil) also known as 1-[[3-(6,7- dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-ethoxyphenyl]sulphonyl]-4- methylpiperazine (see EP-A-0463756); 5-[2-ethoxy-5-(4-ethylpiperazin-1-ylsulphonyl)pyridin-3-yl]-3-ethyl-2-[2-methoxyethyl]-2,6-dihydro- 7H-pyrazolo[4,3-d]pyrimidin-7-one, also known as 1-{6-ethoxy-5-[3-ethyl-6,7-dihydro-2-(2-methoxyethyl)- 7-oxo-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-pyridylsulphonyl}-4-ethylpiperazine (see WO 01/27113, Example 8); S^δ-Acetyl^-butoxy-S-pyridinyO-S-ethyl^^i-ethyl-S-azetidinyO^.Θ-dihydro^W-pyrazoloμ.S- cdpyrimidin-7-one (see WO 01/27112, Example 132); (6R,12aR)-2, 3, 6,7,12, 12a-hexahydro-2-methyl-6-(3,4-methylenedioxyphenyl) - pyrazino[2',1':6,1]pyrido[3,4-b]indole-1 ,4-dione (IC-351 , tadalafil), i.e. the compound of examples 78 and 95 of published international application WO95/19978, as well as the compound of examples 1 , 3, 7 and 8; and 2-[2-ethoxy-5-(4-ethyl-piperazin-1-yl-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1- f][1 ,2,4]triazin-4-one (vardenafil) also known as 1-[[3-(3,4-dihydro-5-methyl-4-oxo-7-propylimidazo[5,1-f]- as-triazin-2-yl)-4-ethoxyphenyl]sulphonyl]-4-ethylpiperazine (i.e. the compound of examples 20, 19, 337 and 336 of published international application WO99/24433); and pharmaceutically acceptable salts thereof. According to a further aspect the present invention provides a composition for the treatment of MED comprising a compound of the present invention and sildenafil. The suitability of any particular cGMP PDE5 inhibitor for use in combination with a compound of the present invention can be readily determined by evaluation of its potency and selectivity using literature methods followed by evaluation of its toxicity, absorption, metabolism, pharmacokinetics, etc in accordance with standard pharmaceutical practice. Preferred cGMP PDE5 inhibitors for use herein have an IC₅₀ at less than 100 nanomolar, more preferably, at less than 50 nanomolar, more preferably still at less than 10 nanomolar. Preferably the cGMP PDE5 inhibitors for use in the pharmaceutical combinations according to the present invention are selective for the PDE5 enzyme. Preferably they have a selectivity of PDE5 over PDE3 of greater than 100 more preferably greater than 300. More preferably the PDE5 has a selectivity over both PDE3 and PDE4 of greater than 100, more preferably greater than 300. Selectivity ratios may readily be determined by the skilled person. !C₅₀ values for the PDE3 and PDE4 enzyme may be determined using established literature methodology, see S A Ballard et al, Journal of Urology, 1998, vol. 159, pages 2164-2171. Preferred herein are NEP inhibitors wherein said NEP is EC 3.4.24.11 and more preferably wherein said NEP inhibitor is a selective inhibitor for EC 3.4.24.11 , more preferably a selective NEP inhibitor is a selective inhibitor for EC 3.4.24.11 , which has an IC₅₀ of less than 10OnM (e.g. ompatrilat, candoxatril, candoxatrilat, sampatrilat). Suitable NEP inhibitor compounds are described in EP-A- 1097719. Particularly preferred NEPi compounds for use as auxiliary agents in the treatment of MED according to the present invention are those described in International Patent application WO 02/079143. Especially preferred is (S)-2-[(1-{[3-(4-chlorophenyl)propyl]-carbamoyl}cyclo-pentyl)methyl]-4- methoxybutanoic acid or a pharmacuetically acceptable salt such as the sodium salt thereof as detailed at Example 22 in WO 02/079143 (U.S. Application No. 10/096218). According to a further aspect the present invention provides a composition for the treatment of MED comprising a compound of the present invention and (S)-2-[(1-{[3-(4- chlorophenyl)propyl]carbamoyl}cyclo-pentyl)methyl]-4-methoxybutanoic acid. According to yet a further aspect of the present invention, there is provided use of a compound of the present invention for the treatment of female sexual dysfunction (FSD). According to another aspeGt of the present invention, there is provided use of a compound of the present invention and one or more additional active agents for the treatment of female sexual dysfunction (FSD). Preferably, the one or more additional active agents is/are selected from the group consisting of: 1) estrogen receptor modulators (e.g., estrogen agonists and/or estrogen antagonists); 2) testosterone replacement agents and/or testosternone (Tostrelle) and/or dihydrotestosterone and/or dehydroepiandrosterone (DHEA) and/or a testosterone implant; 3) estrogen, estrogen and medroxyprogesterone or medroxyprogesterone acetate (MPA) (as a combination), or a combination of estrogen and a methyl testosterone hormone replacement therapy agent; 4) one or more dopaminergic agents; 5) one or more NPY (neuropeptide Y) inhibitors; 6) one or more melanocortin receptor modulators or melanocortin enhancers; 7) one or more NEP (neutral endopeptidase) inhibitors; 8) one or more PDE (phosphodiesterase) inhibitors; and 9) one or more bombesin receptor modulators. Preferably, the FSD is female sexual arousal disorder (FSAD). Alternatively, the FSD is female orgasmic disorder (FOD). In a further alternative, the FSD is hypoactive sexual desire disorder (HSDD). In yet a further alternative, the FSD is a sexual pain disorder, preferably Dyspareunia or Vaginismus. Examples of estrogen receptor modulators include raloxifene or lasofoxifene, (-)-cis-6-phenyl-5- [4-(2-pyrrolidin-1 -yl-ethoxy)-phenyl]-5,6,7,8-tetrahydronaphthalene-2-ol and pharmaceutically acceptable salts thereof (compound (a) below), the preparation of which is detailed in US Patent No. 5,552,412 (equivalent to WO 96/021656) and incorporated herein by reference.

Compound (a) An example of a testosterone replacement agent is dehydroandrostendione. Examples of hormone replacement therapy agents include Premarin, Cenestin, Oestrofeminal, Equin, Estrace, Estrofem, EIIeste Solo, Estring, Eastraderm TTS, Eastraderm Matrix, Dermestril, Premphase, Preempro, Prempak, Premique, Estratest, Estratest HS, and Tibolone. Examples of dopaminergic agents include apomorphine or a selective D2, D3 or D2/D₃agonist such as, pramipexole and ropirinol (as claimed in WO-0023056), L-Dopa or carbidopa, PNU95666 (as disclosed in WO-0040226 and US Patent No. 6,455,564). Examples of NPY (neuropeptide Y) inhibitors include NPY1 or NPY5 inhibitors, preferably NPY1 inhibitor. Preferably, said NPY inhibitors (including NPY Y1 and NPY Y5) having an IC50 of less than 10OnM, more preferably less than 50 nM. Suitable NPY, and in particular NPY1 inhibitor compounds, are described in EP-A-1097718. Examples of a melanocortin receptor agonist or modulator or melanocortin enhancer include melanotan II, PT-14, PT-141 or compounds disclosed in WO-09964002, WO-00074679, WO-09955679, WO-00105401 , WO-00058361 , WO-00114879, WO-00113112 or WO-09954358. Suitable NEP inhibitors are as described hereinabove. According to a further aspect, the present invention provides a composition for the treatment of FSD comprising a compound of the present invention and (S)-2-[(1-{[3-(4- chlorophenyl)propyl]carbamoyl}cyclo-pentyl)methyl]-4-methoxybutanoic acid. Preferred PDE inhibitors include a PDE 2, 3, 4, 5, 7 or 8 inhibitor, preferably a PDE2 or PDE5 inhibitor and more preferably a PDE5 inhibitor (as described hereinabove), most preferably sildenafil. According to a further aspect, the present invention provides a composition for the treatment of FSD comprising a compound of the present invention and sildenafil. Preferred examples of one or more of bombesin receptor antagonists or modulators would be antagonists or modulators for BB₁, including those described in WO 02/40008. Also preferred are bombesin BB₂, BB₃, or BB₄ receptor antagonists. Preferred bombesin receptor antagonists are also mentioned as "auxiliary agents" in WO 02/47670. It should be noted that a full list of possible "additional active agents" can be found in WO 02/ 47670 and are described as "auxiliary agents" therein. In accordance with yet another aspect of the present invention, other 5-HT_2c receptor agonists may be used in addition to a compound of the present invention. Such 5-HT₂₀ receptor agonists include, but are not limited to, those disclosed in Chaki and Nakazato - Expert Opin. Ther. Patents (2001). 11(11 ):1677-1692 (see especially Section 3.9 - 5HT₂₀ on page 1687 and Figure 7 on page 1686), or Isaac - Drugs of the Future (2001 ), 26(4):383-393 (see especially Figure 2 on page 385). For the avoidance of doubt, the aforementioned publications are incorporated herein by reference in their entireties. Preferably, the 5-HT_2c receptor agonists are selective 5-HT_2c receptor agonists. As discussed above, the term "selective" as used herein with respect to methods of treatment means "functionally selective". Thus, according to another aspect, the present invention additionally provides the use of the compounds of the present invention as 5-HT_2c receptor agonists, preferably selective 5-HT_2c receptor agonists, for the treatment of FSD, preferably FSAD, FOD, HSDD or a sexual pain disorder (such as Dyspareunia or Vaginismus). According to the methods of the invention, a compound of the present invention or a combination of a compound of the present invention and at least one additional pharmaceutical agent is administered to a subject in need of such treatment, preferably in the form of a pharmaceutical composition. In the combination aspect of the invention, the compound of the present invention and at least one other pharmaceutical agent (such as those described above) may be administered either separately or in the pharmaceutical composition comprising both. It is generally preferred that such administration be oral. However, if the subject being treated is unable to swallow, or oral administration is otherwise impaired or undesirable, parenteral or transdermal administration may be appropriate. According to the methods of the invention, when a combination of a compound of the present invention and at least one other pharmaceutical agent are administered together, such administration can be sequential in time or simultaneous with the simultaneous method being generally preferred. For sequential administration, a compound of the present invention and the additional pharmaceutical agent can be administered in any order. It is generally preferred that such administration be oral. It is especially preferred that such administration be oral and simultaneous. When a compound of the present invention and the additional pharmaceutical agent are administered sequentially, the administration of each can be by the same or by different methods. According to the methods of the invention, a compound of the present invention or a combination of a compound of the present invention and at least one additional pharmaceutical agent (referred to herein as a "combination") is preferably administered in the form of a pharmaceutical composition. Accordingly, a compound of the present invention or a combination can be administered to a patient separately or together in any conventional oral, rectal, transdermal, parenteral, (for example, intravenous, intramuscular, or subcutaneous) intracisternal, intravaginal, intraperitoneal, intravesical, local (for example, powder, ointment or drop), or buccal, or nasal, dosage form. Compositions suitable for parenteral injection generally include pharmaceutically acceptable sterile aqueous or nonaqueous solutions, dispersions, suspensions, or emulsions, and sterile powders for reconstitution into sterile injectable solutions or dispersions. Examples of suitable aqueous and nonaqueous carriers or diluents (e.g., solvents, or vehicles) include water, ethanol, polyols (propylene glycol, polyethylene glycol, glycerol, and the like), suitable mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants. These compositions may also contain excipients such as preserving, wetting, emulsifying, and dispersing agents. Prevention of microorganism contamination of the compositions can be accomplished with various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, and the like. It may also be desirable to include isotonic agents, for example, sugars, sodium chloride, and the like. Prolonged absorption of injectable pharmaceutical compositions can be brought about by the use of agents capable of delaying absorption, for example, aluminum monostearate and gelatin. Solid dosage forms for oral administration include capsules, tablets, powders, and granules. In such solid dosage forms, a compound of the present invention or a combination is admixed with at least one inert customary pharmaceutical excipient, diluent or carrier, such as sodium citrate or dicalcium phosphate or (a) fillers or extenders (e.g., starches, lactose, sucrose, mannitol, silicic acid and the like); (b) binders (e.g., carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose, acacia and the like); (c) humectants (e.g., glycerol and the like); (d) disintegrating agents (e.g., agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain complex silicates, sodium carbonate and the like); (e) solution retarders (e.g., paraffin and the like); (f) absorption accelerators (e.g., quaternary ammonium compounds and the like); (g) wetting agents (e.g., cetyl alcohol, glycerol monostearate and the like); (h) adsorbents (e.g., kaolin, bentonite and the like); and/or (i) lubricants (e.g., talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate and the like), in the case of capsules and tablets, the dosage forms may also comprise buffering agents. Solid compositions of a similar type may also be used as fillers in soft or hard filled gelatin capsules using such excipients as lactose or milk sugar, as well as high molecular weight polyethylene glycols, and the like. Solid dosage forms such as tablets, dragees, capsules, and granules can be prepared with coatings and shells, such as enteric coatings and others well known in the art. They may also contain opacifying agents, and can also be of such composition that they release the compound of the present invention and/or the additional pharmaceutical agent in a delayed manner. Examples of embedding compositions that can be used are polymeric substances and waxes. The drug can also be in micro¬ encapsulated form, if appropriate, with one or more of the above-mentioned excipients. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs. In addition to the compound of the present invention or the combination, the liquid dosage form may contain inert diluents commonly used in the art, such as water or other solvents, solubilizing agents and emulsifiers, as for example, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-butylene glycol, dimethylformamide, oils (e.g., cottonseed oii, groundnut oil, corn germ oil, olive oil, castor oil, sesame seed oil and the like), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, or mixtures of these substances, and the like. Besides such inert diluents, the liquid compositions can also include excipients, such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents. Suspensions, in addition to the compound of the present invention or the combination, may further comprise suspending agents, e.g., ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar, and tragacanth, or mixtures of these substances, and the like. Compositions for rectal or vaginal administration preferably comprise suppositories, which can be prepared by mixing a compound of the present invention or a combination with suitable non-irritating excipients or carriers, such as cocoa butter, polyethylene glycol or a suppository wax which are solid at ordinary room temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity thereby releasing the active component(s). Dosage forms for topical administration of the compounds of the present invention and combinations may comprise ointments, powders, sprays and inhalants. The drugs are admixed under sterile condition with a pharmaceutically acceptable carrier, and any preservatives, buffers, or propellants that may be required. Ophthalmic formulations, eye ointments, powders, and solutions are also intended to be included within the scope of the present invention. The dosage of the additional pharmaceutical agent will be generally dependent upon a number of factors including the health of the subject being treated, the extent of treatment desired, the nature and kind of concurrent therapy, if any, and the frequency of treatment and the nature of the effect desired. In general, the dosage range of an anti-obesity agent is in the range of from about 0.001 mg to about 100 mg per kilogram body weight of the individual per day, preferably from about 0.1 mg to about 10 mg per kilogram body weight of the individual per day. However, some variability in the general dosage range may also be required depending upon the age and weight of the subject being treated, the intended route of administration, the particular anti-obesity agent being administered and the like. The determination of dosage ranges and optimal dosages for a particular patient is also well within the ability of one of ordinary skill in the art having the benefit of the instant disclosure. The following paragraphs describe exemplary formulations, dosages, etc. useful for non-human animals. The administration of the compounds of the present invention and combinations can be effected orally or non-orally (e.g., by injection). An amount of a compound of the present invention or combination is administered such that an effective dose is received. Generally, a daily dose that is administered orally to an animal is between about 0.01 and about 1 ,000 mg/kg of body weight, preferably between about 0.01 and about 300 mg/kg of body weight. Conveniently, a compound of the present invention (or combination) can be carried in the drinking water so that a therapeutic dosage of the compound is ingested with the daily water supply. The compound can be directly metered into drinking water, preferably in the form of a liquid, water-soluble concentrate (such as an aqueous solution of a water-soluble salt). Conveniently, a compound of the present invention (or combination) can also be added directly to the feed, as such, or in the form of an animal feed supplement, also referred to as a premix or concentrate. A premix or concentrate of the compound in a carrier is more commonly employed for the inclusion of the agent in the feed. Suitable carriers are liquid or solid, as desired, such as water, various meals such as alfalfa meal, soybean meal, cottonseed oil meal, linseed oil meal, corncob meal and corn meal, molasses, urea, bone meal, and mineral mixes such as are commonly employed in poultry feeds. A particularly effective carrier is the respective animal feed itself; that is, a small portion of such feed. The carrier facilitates uniform distribution of the compound in the finished feed with which the premix is blended. Preferably, the compound is thoroughly blended into the premix and, subsequently, the feed. In this respect, the compound may be dispersed or dissolved in a suitable oily vehicle such as soybean oil, corn oil, cottonseed oil, and the like, or in a volatile organic solvent and then blended with the carrier. It will be appreciated that the proportions of compound in the concentrate are capable of wide variation since the amount of the compound in the finished feed may be adjusted by blending the appropriate proportion of premix with the feed to obtain a desired level of compound. High potency concentrates may be blended by the feed manufacturer with proteinaceous carrier such as soybean oil meal and other meals, as described above, to produce concentrated supplements, which are suitable for direct feeding to animals. In such instances, the animals are permitted to consume the usual diet. Alternatively, such concentrated supplements may be added directly to the feed to produce a nutritionally balanced, finished feed containing a therapeutically effective level of a compound of the present invention. The mixtures are thoroughly blended by standard procedures, such as in a twin shell blender, to ensure homogeneity. If the supplement is used as a top dressing for the feed, it likewise helps to ensure uniformity of distribution of the compound across the top of the dressed feed. Drinking water and feed effective for increasing lean meat deposition and for improving lean meat to fat ratio are generally prepared by mixing a compound of the present invention with a sufficient amount of animal feed to provide from about 10^"3 to about 500 ppm of the compound in the feed or water. The preferred medicated swine, cattle, sheep and goat feed generally contain from about 1 to about 400 grams of a compound of the present invention (or combination) per ton of feed, the optimum amount for these animals usually being about 50 to about 300 grams per ton of feed. The preferred poultry and domestic pet feeds usually contain about 1 to about 400 grams and preferably about 10 to about 400 grams of a compound of the present invention (or combination) per ton of feed. For parenteral administration in animals, the compounds of the present invention (or combination) may be prepared in the form of a paste or a pellet and administered as an implant, usually under the skin of the head or ear of the animal in which increase in lean meat deposition and improvement in lean meat to fat ratio is sought. In general, parenteral administration involves injection of a sufficient amount of a compound of the present invention (or combination) to provide the animal with about 0.01 to about 20 mg/kg/day of body weight of the drug. The preferred dosage for poultry, swine, cattle, sheep, goats and domestic pets is in the range of from about 0.05 to about 10 mg/kg/day of body weight of drug. Paste formulations can be prepared by dispersing the drug in a pharmaceutically acceptable oil such as peanut oil, sesame oil, corn oil or the like. Pellets containing an effective amount of a compound of the present invention, pharmaceutical composition, or combination can be prepared by admixing a compound of the present invention or combination with a diluent such as carbowax, carnuba wax, and the like, and a lubricant, such as magnesium or calcium stearate, can be added to improve the pelleting process. It is, of course, recognized that more than one pellet may be administered to an animal to achieve the desired dose level which will provide the increase in lean meat deposition and improvement in lean meat to fat ratio desired. Moreover, implants may also be made periodically during the animal treatment period in order to maintain the proper drug level in the animal's body. The present invention has several advantageous veterinary features. For the pet owner or veterinarian who wishes to increase leanness and/or trim unwanted fat from pet animals, the instant invention provides the means by which this may be accomplished. For poultry, beef, and swine breeders, utilization of the method of the present invention yields leaner animals that command higher sale prices from the meat industry. Embodiments of the present invention are illustrated by the following Examples. It is to be understood, however, that the embodiments of the invention are not limited to the specific details of these Examples, as other variations thereof will be known, or apparent in light of the instant disclosure, to one of ordinary skill in the art. EXAMPLES Unless specified otherwise, starting materials are generally available from commercial sources such as Aldrich Chemicals Co. (Milwaukee, Wl), Lancaster Synthesis, Inc. (Windham, NH), Acros Organics (Fairlawn, NJ), Maybridge Chemical Company, Ltd. (Cornwall, England), Tyger Scientific (Princeton, NJ), and AstraZeneca Pharmaceuticals (London, England). General Experimental Procedures NMR spectra were recorded on a Varian Unity™ 400 (available from Varian Inc., Palo Alto, CA) at room temperature at 400 MHz for proton, at 100 MHz for ¹³C, and at 376 MHz for ¹⁹F. Chemical shifts are expressed in parts per million (δ) relative to residual solvent as an internal reference. The peak shapes are denoted as follows: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br s, broad singlet; 2s, two singlets. Atmospheric pressure chemical ionization mass spectra (APCI) were obtained on a Fisons™ Platform Il Spectrometer (carrier gas: acetonitrile: available from Micromass Ltd, Manchester, UK). Chemical ionization mass spectra (Cl) were obtained on a Hewlett-Packard™ 5989 instrument (ammonia ionization, PBMS: available from Hewlett-Packard Company, Palo Alto, CA). Electrospray ionization mass spectra (ES) were obtained on a Waters™ ZMD instrument (carrier gas: acetonitrile: available from Waters Corp., Milford, MA). Where the intensity of chlorine or bromine-containing ions are described, the expected intensity ratio was observed (approximately 3:1 for ³⁵CI/³⁷CI-containing ions and 1 :1 for ⁷⁹Br/⁸¹Br-containing ions) and the intensity of only the lower mass ion is given. In some cases only representative ¹H NMR peaks are given. MS peaks are reported for all examples. Optical rotations were determined on a PerkinElmer™ 241 polarimeter (available from PerkinElmer Inc., Wellesley, MA) using the sodium D line (λ = 589 nm) at the indicated temperature and are reported as follows [α]_D ^temp, concentration (c = g/100 ml), and solvent. Melting points were determined on a Thomas Hoover capillary melting point apparatus and are reported uncorrected. Column chromatography was performed with either Baker™ silica gel (40 μm; JT. Baker, Phillipsburg, NJ) or Silica Gel 50 (EM Sciences™, Gibbstown, NJ) in glass columns or in Flash 40 Biotage™ columns (ISC, Inc., Shelton, CT) under low nitrogen pressure. Preparative thin-layer chromatography was performed using Analtech silica gel GF with UV254 indicator (Analtech Inc., Newark, DE) 20 cm x 20 cm X 1mm plates. When needed multiple plates are used. After eluting the plates with the indicated solvent, the desired band is marked under UV light, and scrapped off. The desire product is extracted from the silica using a polar solvent system (e.g., 20% methanol in methylene chloride). As used herein, the following acronyms have the corresponding meanings. THF - tetrahydrofuran DMF - dimethylformamide DMSO - dimethylsulfoxide NBS - Λ/-bromosuccinimide BOC - ferf-butoxycarbonyl NMP - N-methyl-2-pyrrolidinone dppf - 1 ,1'-bis(diphenylphosphino)ferrocene dppb - 1 ,4-bis(diphenylphosphino)butane Preparation of Intermediates Preparation of Intermediate 1-Allyloxy-2-bromo-benzene (1-1 a):

Ma To a solution of 2-bromo-phenol (14.21 g, 82 mmol) in DMF (20 ml) was added K₂CO₃ (34.05 g, 246 mmol) and allyl bromide (14.2 ml, 164 mmol). The reaction mixture was stirred in a pressure tube at 108 ⁰C for 2 days. After cooled down to room temperature, the reaction mixture was poured into ice water and extracted with ethyl acetate (3 x 100 ml). The combined extracts were washed with water (4 x 100 ml), dried and concentrated. The yellow residue was passed through a short pad of silica gel eluted with 500 ml 25% CH₂CI₂/Hexane. The filtrate was concentrated to give the title compound VAa as a colorless oil (17.4 g). ¹H NMR (400 MHz, CDCI₃) δ 7.53 (d, 1 H); 7.24 (t, 1 H); 6.89 (d, 1 H); 6.86 (t, 1 H); 6.06 (m, 1 H); 5.50 (d, 1H); 5.30 (d, 1 H); 4.60 (d, 2H). MS (APCQ CaIc: 212.0, Found 211.1 (M-1).

Preparation of Intermediate 2-Allyl-6-bromo-Dhenol (1-1 b):

1-1 b The solution of 1-allyloxy-2-bromo-benzene M_a. (17.4 g, 81 mmol) in 10 ml DMF was stirred in a pressure tube at 203 ⁰C for 6 hours, then at 195 °C for 15 hours. After cooled down to room temperature, the reaction mixture was poured into water (100 ml) and extracted with ethyl acetate (3 x 70 ml). The combined extracts were washed with water (4 x 100 ml), dried and concentrated. The residue was purified by flash chromatography (silica, 5% ethyl acetate/hexane) to give the title compound I₁Ib (8.96 g). ¹H NMR (400 MHz, CDCI₃) δ 7.32 (d, 1 H); 7.07 (d, 1H); 6.75 (t, 1H); 6.00 (m, 1H); 5.10 (d, 2H); 3.44 (d, 2H). MS (APCI^") CaIc: 212.0, Found 211.1 (M-1).

Preparation of Intermediate (7-Bromo-2,3-dihvdro-benzofuran-2-yl)-methanol (l-1c):

1-1 c To the solution of 2-allyl-6-bromo-phenol .Mb (876 mg, 4.09 mmol) in methylene chloride (8 ml) was added m-chloroperbenzoic acid (1.28 g, 5.73 mmol). The resulting mixture was stirred at room temperature for 14 hours. The solution turned yellow with precipitate formation. The solution was diluted with ethyl acetate (40 ml) and washed with saturated NaHCO₃, saturated sodium thiosulfate and brine. The organic layer was dried and concentrated to give 2-bromo-6-oxiranylmethyl-phenol as a yellow oil, which was used in the next step without purification. To the solution of 2-bromo-6-oxiranylmethyl-phenol (4.09 mmol) in DMSO (5 ml) was added KOH (305.2 mg, 5.44 mmol) in H₂O (1.5 ml). The reaction mixture was stirred at room temperature for 19 hours. The reaction mixture was then diluted with H₂O (30 ml) and extracted with ethyl acetate (3 x 30 ml). The combined ethyl acetate extracts were washed with brine, dried and concentrated. The crude product was purified by chromatography (silica, 25% ethyl acetate/hexane) to give the title compound l-1c (586 mg). ¹H NMR (400 MHz, CDCI₃) δ 7.20 (d, 1 H); 7.05 (d, 1 H); 6.68 (t, 1 H); 4.92 (m, 1 H); 3.84 (d, 1 H); 3.70 (dd, 1 H); 3.267 (dd, 1 H), 3.11 (dd, 1 H). MS (APCI^") CaIc: 228.0, Found 227.1 (M-1 ).

Preparation of Intermediate Methanesulfonic acid 7-bromo-2,3-dihvdro-benzofuran-2-ylmethyl ester (1-1 d):

Md To the solution of (7-bromo-2,3-dihydro-benzofuran-2-yl)-methanol (Hc: 586 mg, 2.56 mmol) in methylene chloride (5 ml) was added triethylamine (535 microliters, 3.33 mmol) and methanesulfonyl chloride (257.5 microliters, 3.84 mmol). The reaction mixture was stirred at room temperature for 3 hours. The reaction was then quenched with 40 ml water. The aqueous solution was extracted with ethyl acetate (3 x 30 ml). The combined ethyl acetate extracts were washed with water, brine, dried and concentrated. The crude product was purified by chromatography (silica, 3% ethyl acetate/hexane) to give the title compound Hd as a white solid (668 mg). ¹H NMR (400 MHz, CDCI₃) δ7.22 (d, 1 H); 7.07 (d, 1 H); 6.72 (t, 1 H); 5.08 (m, 1 H); 4.39 (m, 2H), 3.40 (m, 1H); 3.04 (dd, 1H). MS (APCI^") CaIc: 306.0, Found 305.1 (M-1).

Preparation of Intermediate Methanesulfonic acid 7-(4-chloro-phenyl)-2.3-dihvdro-benzofuran-2-ylmethyl ester (l-1e):

He A solution of methanesulfonic acid 7-bromo-2,3-dihydro-benzofuran-2-ylmethyl ester (Hd: 86 mg, 0.28 mmol) in ethylene glycol dimethyl ether (2 ml) was deoxygenated by passing nitrogen through the mixture for 2 minutes. Pd(PPh₃)₄ (32.5 mg, 0.028 mmol, 10 mole%) was then added to the solution. After stirring at room temperature for 10 minutes, a deoxygenated ethanol (1 ml) solution of 4- chlorophenylboronic acid was added. The resulting reaction mixture was stirred at room temperature for 10 minutes. An aqueous solution of Na₂CO₃ (0.84 ml, 2 M) was deoxygenated and added to the reaction mixture, which was stirred at room temperature for 5 minutes, then stirred at reflux (82⁰C) for 18 hours. After cooled down to room temperature, the reaction was quenched with 30 ml of water and extracted with ethyl acetate (3 x 15 ml). The combined extracts were dried and concentrated. The crude product was purified by chromatography (silica, 25% ethyl acetate/hexane) to give the title compound (He: 75 mg). ¹H NMR (400 MHz, CDCI₃) δ 7.58 (d, 2H); 7.37 (d, 2H); 7..35 (t, 1 H); 7.24 9d, 1 H); 6.95 (t, 1 H); 5.08 (m, 1 H); 4.49 (d, 2H); .3.40 (dd, 1 H); 3.10 (dd, 1 H); 2.89, (s, 3H). MS (APCI^") CaIc: 338.0, Found 337.2 (M-1).

Preparation of Intermediate (7-Bromo-5-chloro-2.3-dihvdro-benzofuran-2-yl)-methanol (1-1 a-2):

1-1 a-2 (5-Chloro-2,3-dihydro-benzofuran-2-yl)-methanol was prepared using procedures analogous to those described above for the preparation of intermediate 1-1 c except starting with 2-allyl-4-chloro-phenol. To a solution of (5-chloro-2,3-dihydro-benzofuran-2-yl)-methanol (924 mg, 5.0 mmol) in DMF (5 ml) was added Λ/-bromosuccinimide (980 mg, 5.5 mmol). The mixture was allowed to stir at room temperature for 5.5 days. An additional amount of N-bromosuccinimide (98 mg, 0.55 mmol) was added. The mixture was stirred at 86⁰C for 5 hours, cooled to room temperature, poured into H₂O (100 ml) and extracted with ethyl acetate (3 X 40 ml). The combined organic extracts were washed with H₂O (4 X 50 ml), brine, dried and concentrated in vacuo. The crude product was purified by preparative TLC eluting with 7% ethyl acetate in methylene chloride to give the title compound 1-1 a-2 as a white solid (975 mg). MS (APCQ: CaIc. 261.9, Found 261.2 (M-1).

Preparation Intermediate 1-(7-Bromo-2,3-dihvdro-benzofuran-2-ylmethyl)-4-BOC-DiDerazine (l-2a):

l-2a To a solution of methanesulfonic acid 7-bromo-2,3-dihydro-benzofuran-2-ylmethyl ester 1-1 d (160 mg, 0.523 mmol) in acetonitrile (3 ml) was added BOC-piperazine (292 mg, 1.57 mmol) and potassium carbonate (145 mg, 1.05 mmol). The mixture was heated at reflux for 2 days. The reaction mixture was cooled to room temperature, filtered and the filtrate was concentrated in vacuo. The crude product was purified by preparative TLC eluting with 1 % methanol in methylene chloride to afford the title compound U 2a as a colorless oil (169 mg). MS (ES^+") CaIc: 396.1 , Found: 397.3 (M+1).

Preparation of lntermediate-fJ-β-Chloro-phenvD-Σ.S-dihvdro-benzofuran^-ylmethyll^-BOC-piperazine (I- 2t&:

l-2b A mixture 1 -(7-Bromo-2,3-dihydro-benzof uran-2-vlmethvl)-4-BOC-piperazine l-2a (36 mg, 0.091 mmol), 2-chlorophenyl boronic acid (28.4 mg, 0.181 mmol), Pd(PPh₃)₄ (8.4 mg, 0.0073 mmol), and aqueous potassium carbonate (0.227 ml, 2M) in ethylene glycol dimethyl ether (4 ml) was deoxygenated for 1 minute. The reaction mixture was stirred at 84°C for 20 hours. The mixture was cooled to room temperature, filtered and the filtrate was concentrated in vacuo. The crude product was purified by Preparative TLC eluting with 1.5 % Methanol in methylene chloride to afford the title compound Hb (25 mg). MS (ES^+") CaIc: 428.2, Found: 429.3 (M+1 ).

Preparation of Intermediate C-(5-Bromo-7-chloro-2,3-dihvdro-benzofuran-2-yl)-N-BOC-methylamine (I- 3a):

l-3a A solution of C-(7-chloro-2,3-dihydro-benzofuran-2-yl)-N-BOC-methylamine (276 mg, 0.978 mmol) in DMF (4 ml) was treated with Λ/-bromosuccinimide (209 mg, 1.17 mmol) and let stir for 16 hours at ambient temperature. LC/MS indicated disappearance of starting material. The reaction was quenched with water and was partitioned between ethyl acetate and water. The aqueous layer was extracted twice with ethyl acetate. The organic extracts were combined, dried over sodium sulfate, filtered and concentrated in vacuo to provide the crude material. The crude material was dissolved in methylene chloride and washed with water (3x). The organic layer was collected, dried, filtered and concentrated in vacuo to provide the title compound J₁Sa (320 mg). MS (ES^+") CaIc: 361.0, Found: 262.2 (M+1 -BOC).

Preparation of Intermediate C-[7-Chloro-5-(2,4-dichloro-phenyl)-2.3-dihvdm-benzofuran-2-yll-N-Boc- methylamine (l~3b):

To a deoxygenated solution of C-(5-Bromo-7-chloro-2,3-dihydro-benzofuran-2-yl)-N-BOC- methylamine l-3a (50 mg, 0.139 mmol) in dioxane (2 mL) was add Pd(PPh₃)₄ (8 mg, 0.07 mmol). The mixture was stirred at room temperature for 5 minutes. To which was added 2,4-dichlorophenylboronic acid (40 mg, 0.21 mmol) and deoxygenated solution of aqueous K₂CO₃ (2.0 M, 139 ml, 0.278 mmol). The resulting mixture was stirred at reflux temperature for 5 hours. The reaction mixture was then cooled to ambient temperature and filtered through a pad of celite. The filtrate was concentrated in vacuo. The residue was dissolved in a 1 :1 mixture of DMSO (500 microliters) to DMF (500 microliters). The crude material was purified using a Shimadzu preparative HPLC. A XTERA 50 X 50 mm column was used eluting with a gradient of 15 %, 0.1 % formic acid in acetonitrile (85 %, O.I % aqueous formic acid) to 100 %, 0.1 % formic acid in acetonitrile (0 %, 0.1 % aqueous formic acid) over 6 minutes with a flow rate of 75 ml/minute detecting at a wavelength of 220 nm. The fractions were collected and concentrated in vacuo to afford the title compound Hb (42.0 mg). MS (ES^+') CaIc: 428.2, Found: 429.3 (M+1).

Preparation of Intermediate C-r7-Chloro-5-(2.4-dichloro-phenyl)-2,3-dihvdro-benzofuran-2-yll-methylamine (l-3c):

A solution of C-[7-Chloro-5-(2,4-dichloro-phenyl)-2,3-dihydro-benzofuran-2-yl]-N-BOC- methylamine l-3b (42 mg, 0.098 mmol) in methylene chloride (2 ml) was treated with trifluoroacetic acid (75.5 microliters, 0.970 mmol). The reaction mixture was stirred at ambient temperature for 8 hours. The reaction mixture was then quenched with saturated aqueous sodium bicarbonate and extracted with methylene chloride (3x). The organic extracts were combined, dried over sodium sulfate, filtered and concentrated in vacuo to afford the title compound I -3c as the free base (35 mg). MS (ES^+") CaIc: 327.0, Found: 328.2 (M+1).

Preparation of Intermediate 2-Hvdroxymethyl-2,3-dihvdro-benzofuran-7~ol (l-4a):

l-4a To a solution of (7-benzyloxy-2,3-dihydro-benzofuran-2-yl)-methanol ( 1.7 g, 6.64 mmol) in a mixture of MeOH and EtOAc (MeOH/EtOAc = 2/1 , 12 ml) was added Pearlman's catalyst (165 mg). The mixture was hydrogenated under 40 psi hydrogen pressure at room temperature for 19 hours. The solution was filtered through a pad of celite and concentrated to give the title compound (14a: 1.08 g) which was used in the next step without purification. MS (ES^+") CaIc: 166.1 , Found: 167.1 (M+1).

Preparation of Intermediate [7-(3-chloro-phenoxy)-2,3-dihvdro-benzofuran-2-ylhmethanol (l-4b):

To a solution of 2-hydroxymethyl-2,3-dihydro-benzofuran-7-ol (Ha: 50 mg, 0.3 mmol) in CH₂CI₂ was added Cu(OAc)₂ (55 mg, 0.3 mmol), 3-chlorophenyl boronic acid (94 mg, 0.602 mmol), Et₃N (0.21 ml, 1.55 mmol) and 4A° molecular sieves. The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was filtered through celite and concentrated. The product was purified by preparative TLC (10% EtOAc in Hexane) to give the title compound (Hb: 30 mg). MS (ES^+") CaIc: 276.1 , Found: 277.1 (M+1).

Preparation of Intermediate 1-(7-Bromo-2,3-dihvdro-benzofuran-2-yl)-ethanol (l-5a):

To a cooled solution of oxalyl chloride (2M in CH₂CI₂, 0.26 ml, 0.52 mmol) at -78⁰C was added dropwise DMSO (0.1 ml, 1.41 mmol). The resulting mixture was stirred at -78 C for 10 min. To which was added dropwise a solution of (7-Bromo-2,3-dihydro-benzofuran-2-yl)-methanol (106 mg, 0.47 mmol) in CH₂CI₂ (1 ml). The mixture was stirred at -78 C for 50 minutes and to which was added dropwise triethylamine (0.2 ml, 1.43 mmol). After stirring at-78 C for 10 minutes, the solution was warmed to room temperature and poured to water (30 ml). The aqueous solution was extracted with CH₂CI₂ (2 x 20 ml). The combined organic extracts were washed with 1 N HCI, saturated sodium bicarbonate, dried and concentrated to give 7-Bromo-2,3-dihydro-benzofuran-2-carbaldehyde (104 mg) as a crude product which was used in the next step without purification. To a solution of 7-Bromo-2,3-dihydro-benzofuran-2-carbaldehyde (104 mg) in THF at room temperature was added dropwise CH₃MgBr (3 M in ether, 0.31ml, 0.93 mmol). The resulting mixture was stirred at room temperature for 3 hours, quenched with 0.3 N HCI (30 ml) and extracted with EtOAc (3 x 20 ml). The combined organic extracts were dried and concentrated. The crude product was purified by preparative TLC ( 25% EtOAc in Hexane) to afford the title compound (J^δa: 72 mg). MS (ES^+") CaIc: 242.0, Found: 243.3 (M+1).

Preparation of Intermediate Methanesulfonic acid 7-o-Tolyl-2,3-dihvdro-benzofuran-2-ylmethyl ester (I- 5b):

l-5b The title compound was prepared from the methanesulfonic acid 7-bromo-2,3-dihydro- benzofuran-2-ylmethyl ester (Hd) and 4-methylphenylboronic acid according to the procedure described for the intermediate M-IeV MS (APCI^~) CaIc: 318.1 , Found: 317.0 (M-1).

Preparation of lntermediate(7-p-Tolyl-2,3-dihvdro-benzofuran-2-yl)-acetonitrile (l-5c):

l-5c To a solution of methanesulfonic acid 7-p-tolyl-2,3-dihydro-benzofuran-2-ylmethyl ester (l-5b: 100 mg, 0.31 mmol) in DMF (3 ml) was added NaCN (24 mg, 0.47 mmol). The mixture was stirred at 75°C for 20 hours, cooled to room temperature and poured into H₂O (30 ml). The aqueous solution was extracted with EtOAc (3 x 20 ml), washed with H₂O (3 x 30 ml), brine, dried and concentrated. The product was purified by preparative TLC eluting with 20% of EtOAc in hexane to give the title compound l-5c (21 mg). MS (APCI^") CaIc: 249.1 , Found: 248.2 (M-1).

Preparation of Intermediates (R)-(7-Bromo-2,3-dihvdro-benzofuran-2-yl)-methanol and (1 S)-(7-Bromo-2,3- dihvdro-benzofuran-2-yl)-methanol (l-6a-1 and l-6a-2):

l-6a-1 l-6a-2 The title enantiomeric compounds were prepared by chiral separation of (7-bromo-2,3-dihydro- benzofuran-2-yl)-methanol (Hc) using chiral preparative HPLC (Column: Chiralcel OD; Dimension: 10 cm x 50 cm; Mobile phase: Heptane/EtOH= 90/10; Flow rate: 250 ml/minute). The Expected preparative retention times for the two enantiomers are -23 min (enantiomer 1) and ~ 27 min (enantiomer 2). EnantiomeM : MS (APCC) CaIc: 228.0, Found: 227.2. (M-1). [α] = - 25.4° (c 0.4, CHCI₃). Enantiomer 2: MS (APCI^") CaIc: 228.0, Found: 227.2 (M-1 ). [α] = + 20.8° (c 0.42, CHCI₃).

Preparation of Intermediate (2R)-Methanesulfonic acid-7-bromo-2,3-dihvdro-benzofuran-2yl-methyl ester (l-6b):

/-fib The title compound was prepared from the enantiomer 1 of (7-Bromo-2,3-dihydro-benzofuran-2- yl)-methanol and methanesulfonyl chloride (l-6a-1 ) according to the procedure described for the intermediate I₁Id- MS (APCI^") CaIc: 306.0, Found: 305.1. (M-1 ).

Preparation of Intermediate (2R)-4-(7-Bromo-2.3-dihvdro-benzofuran-2-ylmethyl)-DiDerazine-1-carboxylio acid tert-butyl ester (l-6c):

l-6c The title compound was prepared from (2R)-methanesulfonic acid 7-bromo-2,3-dihydro- benzofuran-2-ylmethyl ester (enantioner 1 , l-6b) and_BOC-piperazine according to the procedure described for the intermediate 1-2a. MS (ES⁺) CaIc: 396.1, Found: 397.3. (M+1).

Preparation of Intermediate (2R)-4-[7-(2-Chloro-phenyl)-2,3-dihvdro-benzofuran-2-ylmethyll-DiDerazine-1- carboxylic acid tert-butyl ester (l-6d):

l-6d The title compound was prepared from (2R)-4-(7-Bromo-2,3-dihydro-benzofuran-2-ylmethyl)- piperazine-1-carboxylic acid tert-butyl ester (l-6c) and 2-chlorophenyl boronic acid according to the procedure described for the intermediate (1-1e). MS (ES⁺) CaIc: 428.1 , Found: 429.3. (M+1). Example 1 Preparation of C-r7-(4-Chloro-ohenyl)-2.3-dihvdro-henzofuran-2-yll-methylamine (1A-1 and 1A-2):

1A-1 1A-2 To the solution of methanesulfonic acid 7-(4-chloro-phenyl)-2,3-dihydro-benzofuran-2-ylmethyl ester JMe (75 mg, 0.22 mmol) in dioxane (2 ml) was added concentrated ammonium hydroxide (1.5 ml). The reaction mixture was stirred at 80⁰C for 67 hours. The reaction mixture was cooled to room temperature and concentrated. The crude product was purified by chromatography (silica, 6% methanol/methylene chloride/4 drops ammonium hydroxide) to give the title compounds 1A-1 and 1A-2 (43 mg). ¹H NMR (400 MHz, CDCI₃) δ7.62 (d, 2H); 7.36 (d, 2H); 7.24 (d, 1 H); 7.12 (d, 1 H); 6.90 (t, 1 H); 4.85 9m, 1 H); 3.30 (dd, 1 H), 2.95, (m 3H); 1.83 (br, 2H). MS (ES⁺) CaIc: 259.08, Found: 260.2 (M+1 ). Two enantiomers were separated by chiral separation using preparative HPLC (Column: chiralcel OD; Dimension: 5 cm x 50 cm; Mobile phase: heptane/ethanol= 85/15, Flow rate: 70 mL/min). The Expected preparative retention times for the two enantiomers are -18 min (Enantiomer 1) and ~ 24 min (Enantiomer 2). Enantiomer 1 : MS (APCI⁺) CaIc: 259.1 , Found: 260.3 (M+1). Enantiomer 2: MS (APCI⁺) CaIc: 259.1 , Found: 260.3 (M+1 ).

Preparation of C-(7-Phenyl-2,3-dihvdro-benzofuran-2-yl)-methylamine (1B-1 and 1B-2):

1B-1 1 B-2 Two enantiomers were prepared by chiral separation of C-(7-phenyl-2,3-dihydro-benzofuran-2-yl)- methylamine using chiral preparative HPLC (Column: Chiralpak AD; Dimension: 10 cm x 50 cm; Mobile phase: heptane/isopropyl alcohol= 95/5, Flow rate: 275 ml/minute). The Expected preparative retention times for the two enantiomers are -46 minutes (enantiomer 1 ) and ~ 61 minutes (enantiomer 2). Enantiomer 1 : MS (ES⁺) CaIc: 225.1 , Found: 226.3. (M+1). [α] = -9.89° (c 0.47, CHCI₃). Enantiomer 2: MS (ES⁺) CaIc: 225.1 , Found: 226.3 (M+1). [α] = +7.63° (c 0.49, CHCI₃).

Preparation of C-(7-Phenyl-2,3-dihvdro-benzofuran-2-yl)-methylamine hydrochloride (1B-3): Enantiomer 1 of C-(7-phenyl-2,3-dihydro-benzofuran-2-yl)-methylamine (64 mg, 0.284 mmol) in CH₂CI₂ (2 ml) was added HCI (4.0 M in dioxane, 85 microliters, 0.34 mmol). The resulting mixture was stirred at room temperature for 5 minutes and hexane (10 ml) was added. The white solid was collected by filtration and dried to afford the title compound 1 B-3 (64 mg) as a white solid. MS (ES⁺) CaIc: 225.1 , Found: 226.3 (M+1). The compounds listed in Table 1 below were prepared using procedures analogous to those described above for the synthesis of Compound 1 A-1 and 1 A-2 using the appropriate starting materials which are available commercially, prepared using preparations well-known to those skilled in the art, or prepared in a manner analogous to routes described above for other intermediates. Table 1

Example 2 Preparation of 2-(7-o-Tolyl-2,3-dihvdro-benzofuran-2-yl)-ethylamine (2A):

ZA To a solution of (7-p-tolyl-2,3-dihydro-benzofuran-2-yl)-acetonitrile (l-5c: 21 mg, 0.084 mmol) in THF (4 ml) was added borane-methyl sulfide complex (5M in ethyl ether, 0.135 ml, 0.673 mmol). The mixture was stirred at reflux temperature for 1.5 hours, cooled to room temperature and quenched by adding dropwise MeOH. The solution was concentrated and the residue was partitioned between EtOAc and saturated NaHCO₃. The aqueous solution was extracted with EtOAc (2 x 20 ml). The combined organic extracts were dried and concentrated. The product was purified by preparative TLC (MeOH :CH₂CI₂: NH₄OH = 8: 92: 1 ) to give the title compound (2A: 9 mg) as a white solid. MS (ES^+") CaIc: 253.2, Found: 254.3 (M+1 ).

The compounds listed in Table 2 below were prepared using procedures analogous to those described above for the synthesis of Compound 2A using the appropriate starting materials which are available commercially, prepared using preparations well-known to those skilled in the art, or prepared in a manner analogous to routes described above for other intermediates. Table 2

Example 3 Preparation of (2R)-1-l7-(2-Chloro-ohenyl)-2,3-clihvdro-benzofuran-2-ylmethyll-piperazine (3A):

1

3A The title compound was prepared from (2R)-4-[7-(2-chloro-phenyl)-2,3-dihydro-benzofuran-2- ylmethyl]-piperazine-1-carboxylic acid tert-butyl ester (]r6d) and trifluoroacetic acid according to the procedure described for the intermediate (1-3c). MS (ES⁺) CaIc: 328.1 , Found: 329.3. (M+1). [α] = - 7.48° (c 0.46, CHCI₃).

Example 4 Preparation of (2S)-1-f7-(2-Chloro-phenyl)-2,3-dihvdro-benzofuran-2-ylmethyll-piperazine (4A):

4A The title compound was prepared from enantiomer 2 of 7-Bromo-2,3-dihydro-benzofuran-2-yl)- methanol (l-6a-2) according to the procedures described for the (2R)-1-[7-(2-chloro-phenyl)-2,3-dihydro- benzofuran-2-ylmethyl]-piperazine (3A). MS (ES⁺) Caic: 328.1 , Found: 329.3. (M+1). [α] = + 6.31° (c 0.32, CHCI₃). The compounds listed in Table 3 below were prepared using procedures analogous to those described above for the synthesis of Compound 4A using the appropriate starting materials which are available commercially, prepared using preparations well-known to those skilled in the art, or prepared in a manner analogous to routes described above for other intermediates. Table 3

5A A mixture of methanesulfonic acid 7-(2-chloro-phenyl)-2,3-dihydro-benzofuran-2-ylmethyl ester J₁ 2d (20 mg, 0.059 mmol), cyclopropyl amine (13.5 mg, 0.236 mmol), and potassium carbonate (16.3 mg, 0.118 mmol) in acetonitrile (2 mi) was heated in a pressure tube to 100⁰C for 18 hours. LC-MS indicated that the reaction was not complete. To which an excess of cyclopropyl amine (200 microliters) was added. The reaction mixture was heated to 100⁰C for additional 18 hours. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated in vacuo. The residue was dissolved into DMSO (1000 microliters). The crude material was purified using a Shimadzu™ Preparative HPLC. A Waters™ C8 30 X 50 mm column was used eluting with a gradient of 0.1 % formic acid in acetonitrile (100 %, O.I % aqueous formic acid) to 100 %, 0.1 % formic acid in acetonitrile (0 %, 0.1 % aqueous formic acid) over 6 minutes with a flow rate of 40 ml/minute. The fractions were collected and concentrated in vacuo to afford the title compound 5A (8.0 mg). MS (ES⁺) CaIc: 299.1 , Found: 300.3. (M+1 ).

[7-(2-Chloro-phenyl)-2,3-dihydro-benzofuran-2-ylmethyl]-cyclobutyl-amine (5B) was prepared using procedures analogous to those described above for the preparation of Compound 5A. MS (ES⁺) CaIc: 313.1 , Found: 314.3. (M+1 ). Example 6 Preparation of C-(5-Phenyl-2,3-dihvdro-benzofuran-2-yl)-methylamine hydrochloride salt (6A):

6A A solution of C-[7-chloro-5-(2,4-dichloro-phenyl)-2,3-dihydro-benzofuran-2-yl]-methylamine K3c (8 mg, 0.024 mmol) in ethanol (2 ml) was treated with 10 % Pd/C (5mg) and ammonium hydroxide (2 drops). The reaction mixture was loaded onto a Parr shaker. The reaction was run at ambient temperature under hydrogen (40 psi) for 16 hours. The reaction was monitored using LC/MS. The reaction mixture was filtered over a pad of celite eluting with ethanol. The filtrate was concentrated in vacuo to afford the title compound as the hydrochloride salt 6A (8 mg). MS (ES⁺) CaIc: 225.1 , Found: 226.3. (M+1). The compounds listed in Table 4 below were prepared using procedures analogous to those described above for the synthesis of Compound 6A using the appropriate starting materials which are available commercially, prepared using preparations well-known to those skilled in the art, or prepared in a manner analogous to routes described above for other intermediates. Table 4

BIOLOGICAL ASSAYS The utility of the compounds of the present invention in the practice of the instant invention was evidenced by activity in one or more of the protocols described hereinbelow. The following acronyms are used hereinbelow. DMEM - Dulbecco's Modified Eagle Medium HEPES - N-2-hydroxyethyl-piperazine-N'-2-ethane sulfonate EDTA - Ethylenediaminetetraacetic acid EGTA - Ethylene glycol-bis(β-aminoethyl ether)-N,N,N\N'-tetraacetic acid PEI - Polyethyleneimine DMSO - Dimethylsulfoxide Fluo 4-AM™ - Fluorescent probe available from Molecular Probes, Inc., Eugene, OR PerkinElmer™ refers to PerkinElmer Life and Analytical Sciences, Inc., Boston, MA Sigma™ refers to Sigma-Aldrich Corp., St. Louis, MO

5HT_2c Binding Procedure Affinity of compounds at the serotonin 5HT₂₀ binding site is determined by competition binding in Swiss 3T3 mouse cells (available from the American Type Culture Collection (ATCC), Manassas, VA) transfected with the human 5HT_2c receptor against ³H-5HT. Cells are grown in DMEM high glucose medium, (switched to medium containing 10% dialyzed fetal bovine serum 18 hours prior to harvest), harvested, centrifuged, and resuspended in Homogenization buffer (10 mM HEPES, pH 7.5, 1 mM EDTA, 1 mM EGTA containing the following protease inhibitors: 0.1 mg/ml benzamidine (Sigma™ B 6506), 0.1 mg/ml bacitracin (Sigma™ B 0125), 0.005 mg/ml leupeptin (Sigma™ L 8511 ), 0.5 mg/ml aprotinin (Sigma™ A 1153). Cells are incubated in a centrifuge tube on ice for 10 minutes, then homogenized using four 10-second bursts of a Polytron™ homogenizer (Brinkman™, Westbury, NY), and then centrifuged at 1000 x g for 10 minutes at 4 ⁰C. The supernatant was carefully removed and transferred to new centrifuge tubes, then centrifuged for 20 minutes at 25,000 x g at 4 ⁰C. The supernatant was removed and discarded, while the pellet was resuspended in homogenization buffer, then centrifuged for 20 minutes at 25,000 x g at 4 °C. The supernatant was discarded while the pellet (containing membranes) was resuspended in homogenization buffer, and the membranes were aliquoted and frozen at -80 ⁰C. Binding activity of test compounds to the 5HT_2c receptor was determined in 96-well plates containing 2 μl of test compound (in 100% DMSO) then 100 μl of ³H-5HT (Amersham Biosciences, Piscataway, NJ; 2 nM final concentration) which was diluted in assay buffer (50 mM Tris pH 7.7, 10 mM MgCI₂, 3 mM CaCI₂, 1 mM EDTA, 10 μM pargyline, 0.1 % ascorbic acid) followed by 100 μl of membranes (approximately 10 μg membrane protein per well) diluted in assay buffer. 1 μM mianserin was used to calculate non-specific binding. Assay plates were incubated for 60 minutes at 37 ⁰C, after which the assay was terminated by filtration onto UniFilter™ plates (with GF/C filters - from PerkinElmer™) that had been pre-soaked in 0.3% PEL The filterplates were washed 2X with cold wash buffer (50 mM Tris, pH 7.4), then dried, scintillation fluid added and radioactivity determined in a Wallac Microbeta™ plate scintillation counter (PerkinElmer™). Concentration-response curves of the % inhibition of specific binding by test compounds versus the test compound concentration, was used to determine the IC₅₀ for each compound and the Ki value calculated based on the Cheng-Prusof equation (Ki = IC50/ (1+(L/Kd)), where L is the concentration of the radioligand used in the binding assay and the Kd is based on previous saturation studies with the radioligand. 5HT_2a Binding Procedure Affinity of compounds at the serotonin 5HT_2a binding site is determined by competition binding in NIH 3T3 mouse cells transfected with the rat 5HT_2a receptor using 1251-DOI. Cells are grown in DMEM high glucose medium (switched to medium containing 10% dialyzed fetal bovine serum 18 hours prior to harvest), harvested, centrifuged, and resuspended in Homogenization buffer (10 mM HEPES, pH 7.5, 1 mM EDTA, 1 mM EGTA containing the following protease inhibitors: 0.1 mg/ml benzamidine (Sigma™ B 6506), 0.1 mg/ml bacitracin (Sigma™ B 0125), 0.005 mg/ml leupeptin (Sigma™ L 8511 ), 0.5 mg/ml aprotinin (Sigma™ A1153). Cells are incubated in a centrifuge tube on ice for 10 minutes, then homogenized using four 10-second bursts of a Polytron™ homogenizer (Brinkman™), and then centrifuged at 1000 x g for 10 minutes at 4 ⁰C. The supernatant was carefully removed and transferred to new centrifuge tubes, then centrifuged for 20 minutes at 25,000 x g at 4 ⁰C. The supernatant was removed and discarded, while the pellet was resuspended in homogenization buffer, then centrifuged for 20 minutes at 25,000 x g at 4 ⁰C. The supernatant was discarded while the pellet (containing membranes) was resuspended in homogenization buffer, and the membranes were aliquoted and frozen at -80 ⁰C. Binding activity of test compounds was determined in 96-well plates containing 2 μl of test compound (in 100% DMSO) then 100 μl of [¹²⁵I]-DOI (catalog number NEX255, PerkinElmer™ Life Sciences; 0.1 nM final concentration) which had been diluted in assay buffer (50 mM HEPES pH 7.4, 0.5 mM EDTA, 0.5 mM EGTA, 37.5 mM KCI, 2.5 mM MgCI₂) followed by 100 μl of 5HT_2a-expressing membranes which had been diluted in assay buffer. 1 μM mianserin was used to calculate non-specific binding. Assay plates were incubated for 60 minutes at 37 ⁰C, after which the assay was terminated by filtration onto UniFilter™ plates (with GF/C filters - from PerkinElmer™) that had been pre-soaked in 0.3% PEL The filterplates were washed 2X with cold wash buffer (50 mM Tris, pH 7.4), then dried, scintillation fluid added and radioactivity determined in a Wallac Microbeta™ plate scintillation counter (PerkinElmer™). Concentration-response curves of the % inhibition of specific binding by test compounds versus the test compound concentration, was used to determine the IC₅₀ for each compound and the Ki value calculated based on the Cheng-Prusof equation (Ki = IC50/ (1 +(L/Kd)), where L is the concentration of the radioligand used in the binding assay and the Kd is based on previous saturation studies with the radioligand. 5HT_2b Binding Procedure Affinity of compounds for the human 5HT_2b receptor is determined by competition binding using membranes prepared from Chinese hamster ovary (CHO) cells containing the tetracycline operator (FIp-In Trex system - Invitrogen) that were engineered to express the human 5HT_2b receptor. Membranes were prepared from cells that had been incubated in dialyzed fetal bovine calf serum (FBS) for the previous 18 hours, in the presence of 1 μM doxicycline, and the membranes were stored at -80 ⁰C. To prepare the membranes, cells were harvested from flasks by centrifugation, then resuspended in homogenization buffer (10 mM HEPES, pH 7.5, 0.25 M sucrose, 1 mM EDTA, 1 mM EGTA containing the following protease inhibitors: 0.1 mg/ml benzamidine (Sigma™ B 6506), 0.1 mg/ml bacitracin (Sigma™ B 0125), 0.005 mg/ml leupeptin (Sigma™ L 8511 ), 0.5 mg/ml aprotinin (Sigma™ A1153) on ice. Cells are incubated in a centrifuge tube on ice for 10 minutes, then homogenized using four 10-second bursts of a Polytron™ homogenizer (Brinkman™), and then centrifuged at 1000 x g for 10 minutes at 4 ⁰C. The supernatant was carefully removed and transferred to new centrifuge tubes, then centrifuged for 20 minutes at 25,000 x g at 4 ⁰C. The supernatant was removed and discarded, while the pellet was resuspended in homogenization buffer, then centrifuged for 20 minutes at 25,000 x g at 4 ⁰C. The supernatant was discarded while the pellet (containing membranes) was resuspended in homogenization buffer, and the membranes were aliquoted and frozen at -80 ⁰C. The binding assay was set up in 96-well plates, which contained 2 μl of test compound (in 100% DMSO) then 100 μl of ³H-LSD (final concentration = 3 nM) diluted in assay buffer (50 mM Tris pH 7.4, 4 mM CaCi₂ , 0.1 % Ascorbic Acid), followed by the addition of 100 μl of membranes (approximately 15 μg membrane protein, diluted in assay buffer) from 5HT_2b -expressing cells. 1 μM mianserin was used to calculate non-specific binding. The assay plates were incubated at 37 ⁰C for 60 minutes, then the assay was terminated by filtration onto 96-well UniFilter™ plates (with GF/C filters - from PerkinElmer™) which were pre-soaked in 0.3% PEI. The filterplates were washed 2X with cold wash buffer (50 mM Tris, pH 7.4), then dried, scintillation fluid added and radioactivity determined in a Wallac Microbeta™ plate scintillation counter (PerkinElmer™). Concentration-response curves of the % inhibition of specific binding by test compounds versus the test compound concentration, was used to determine the IC₅₀ for each compound and the Ki value calculated based on the Cheng-Prusoff equation (Ki = IC50/ (1+(L/Kd)), where L is the concentration of the radioligand used in the binding assay and the Kd is based on previous saturation studies with the radioligand. Determination of potencies in binding assays provides an indication of the ability of a compound to displace another compound from the active site of the receptor. In other words, binding assays provide information on the ability of a test compound to interact with the receptor, but not on the ability of the compound to activate or block activation of the receptor. Whereas, functional assays are able to provide indication of the compound to activate a receptor or block the activation of the receptor as a consequence of prior binding. Activation or blockade of the activation of the receptor are what leads to the physiological activities of the ligands. Agonistic activity at a receptor and antagonistic activity at a receptor are completely different from one another and lead to very different and often opposing pharmacological responses. Consequently, the following assays provide useful information with respect to the mode of activation. Functional Assays In vitro Functional assays Swiss 3T3 cells expressing r-5HT_2c, r-5HT_2a, h-5HT_2c , h-5HT_2a or CHO cells expressing Tet- inducible h-5HT_2b (co-expressing with GD 16) receptors are seeded at a densities of 12,500 cells / well for 5HT_2c and 5HT_2a cells and at 25,000 cells/well for 5HT_2b cells in 384 well black/clear collagen-coated plates. All cells were grown in culture media supplemented with 10% fetal bovine serum. Twenty four (24) hours later culture media was replaced with media supplemented with 10% dialyzed serum. 5HT_2b cells were induced in the presence of 1 μg/ml doxycyclin in culture media with dialyzed serum. Twenty four (24) hours later the cells are loaded with the calcium sensitive dye, Fluo 4-AM™ (4 μM dissolved in DMSO containing pluronic acid) in serum free DMEM in the presence of probenicid (2.6 mM) for 75 minutes at 37 ⁰C in a CO₂ incubator. Unincorporated dye is removed by washing 3 times with a HEPES- buffer containing probenicid (2.6 mM) using an EMBLA cell washer (final volume 30 μl). Plates are added to a fluorometric imaging plate reader (FLIPR 384™ available from Molecular Devices Corporation) individually and fluorescence measurements are taken every 2 seconds over an 90 seconds period. Test compound additions are made simultaneously to all 384 wells after 20 seconds of baseline recording. Concentration-response curves are generated using XLDA and agonist efficacies are generated as % of the response to 10 μM 5-HT (considered as 100%). Estimation of antagonist potencies (functional Ki's) are generated by measuring inhibition of the test compound response to 5-HT (10 nM for 5-HT_2c and 5HT_2b, 50 nM for 5-HT_2a) and applying the Cheng Prusoff equation. OBESITY AND RELATED DISORDERS Spontaneous Food Intake The following screen is used to evaluate the efficacy of test compounds for inhibiting spontaneous food intake in Sprague-Dawley rats. Male Sprague-Dawley rats may be obtained from Charles River Laboratories, Inc. (Wilmington, MA). The rats are individually housed and fed powdered chow. They are maintained on a 12 hour light/dark cycle and received food and water ad libitum. The animals are acclimated to the vivarium for a period of one week before testing is conducted. Rats are transferred to individual test cages 30 hours before the study. The rats are administered test compound or vehicle alone (no compound) 15-30 minutes prior to the onset of the dark cycle. The test compounds are dosed at ranges between 0.1 and 100 mg/kg depending upon the compound. The standard vehicle is 0.5% (w/v) methylcellulose or 30% β- cyclodextrin in water and the standard route of administration is oral. However, different vehicles and routes of administration are used to accommodate various compounds when required. Food intake is monitored using an automated Columbus Instruments system (Columbus, Ohio). Individual rat food intake is recorded continuously at 10-minute intervals, starting at the time of dosing, for a period of at least 12 hours. Compound efficacy is determined by comparing the food intake pattern of compound-treated rats to vehicle. SCHIZOPHRENIA AND RELATED DISORDERS The compounds of the present invention are useful in the treatment of Schizophrenia and related disorders. This activity can be demonstrated in models using well-established procedures. For example, the compounds of the present invention may be assessed in a number of standard behavioural tests predictive of antipsychotic activity. For example, apomorphine-induced climbing behaviour and hypothermia in mice (see, e.g., Moore, N. A. et al. Psvchopharmacoloqy 94 (2), 263-266 (1988), and 96, 539 (1988)). Conditioned Avoidance Responding (inhibition of CAR) has been a classic and effective test used for the detection of drugs with potential antipsychotic activity, primarily developed to test neuroleptics acting through dopamine receptor blockade). Similarly, d-Amphetamine locomotor (antagonism of the increased activity produced by d-amphetamine to show dopamine receptor blockade) and PCP locomotor (antagonism of the increased activity produced by the activation of dopamine neuronal function by the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist; phencyclidine (PCP)) assays can be used to predict anti-psychotic activity. Compounds of the present invention have been shown to be active in at least one of the following protocols. Locomotor Activity The locomotor activity boxes consist of 48 individual plexiglass behavioral chambers (30cm X 30cm) enclosed in sound attenuating cabinets. A single 10 watt bulb in each cabinet is controlled by a 24 hour timer, which allows the behavioral to be maintained on any light/dark cycle desired. The plexiglass chambers are fitted with grid floors which are divided into quadrants and a metal touchplate positioned 7 cm from the floor on all four walls of the chamber. Horizontal locomotor activity is measured as the number of cross-overs an animal makes from one quadrant to another within its chamber. When the animal stands up (rears) and makes contact with the metal touchplate it is recorded by the computer as vertical locomotor activity. Subjects are placed in the chambers overnight (approx.15 hours) prior to the experiment. The next day each animal is weighed and treated with the test compound and then immediately returned to the test chamber. At a set pretreatment time, subjects are removed from the test chamber and treated with phencyclidine hydrochloride (3.2 mg/kg, sc), or d-Amphetamine sulphate (1 mg/kg, sc) and then immediately returned to the test chamber. Horizontal movements (cross-overs) are recorded by a computer for a three-hour test period. In order to measure spontaneous locomotor activity, each animal is weighed and treated with the test compound one hour prior to being placed in the activity box. The test is always started as soon after the dark cycle (4 pm) as possible so that the effects of the compound can be observed during the animals' most active time. The apparatus is programmed to collect data overnight for a 12-hour period. The computer is programmed to perform statistical analysis at given intervals. A one-way ANOVA is used to determine whether a difference due to treatment exists and is followed by Dunnett's multiple range test to determine differences between the control and experimental groups. Timed intervals of data (cross-overs) are analyzed individually and cumulatively for the duration of the experiment. Conditioned Avoidance Response Male CF rats (Charles River, Fisher-344 strain) are used in all experiments. Weights are approximately 350-400 grams at the time of testing. Animals are housed 2 per cage in environmentally controlled animal quarters (light/dark-4am/4pm). The conditioned avoidance shuttle chambers consist of 8 individual Plexiglas behavior chambers (Coulboum Instruments™) each divided by a guillotine door into two sides, enclosed in sound attenuating cabinets. The Plexiglas chambers are fitted with metal grid floors, which are equipped with scrambled/constant current shockers. Rats are trained to avoid the onset of footshock (1.5 miliampere, preceded for 5 seconds by activation of house lights, que lights, and the opening of the guillotine door) by moving to the opposite side of the chamber. Thirty trials are completed per daily session, and the number of avoidance's (max 30), escapes (max 30), escape failures (max 30), latency to avoid (max 5 sec), latency to escape (max.10 sec), and adaptation crossovers (number of crossovers for a five minute period before the onset of trials, dark chamber) are recorded by the computer program. Inter-trial intervals are 15 seconds with the guillotine door closed. Drug treatment begins (30 minutes prior to session, s.c) when rats have reached criteria of 80% avoidances for a session. Testing is performed during the lights on period of the light/dark cycle, typically between 8am and 10am. Vehicle treatment is performed one day every week and statistical analysis is done comparing each drug treatment on separate days vs. the vehicle treatment that week. Testing is performed during the lights on period of the light/dark cycle, typically between 8am and 10am. The data is analyzed following importation into a spreadsheet using a t-test. SEXUAL DYSFUNCTION Treatment of MED Compounds of the present invention can be screened for effect of penile intracavernosal pressure (ICP) in the conscious male rat according to the methods described hereinbelow. ICP Protocol: Intra cavernosal pressure (ICP) can be measured in the conscious rat by means of telemetric recording. A catheter is surgically implanted into the corpus cavernosum. The end of the catheter is linked to a device, which senses, processes, and transmits information digitally from within the animal. A receiver converts the radio-frequency signal from the implant to a digital pulse stream that is readable by a data collection system. The PC-based system collects telemetred data from the animal. Surgery:- Induce and maintain general anaesthesia using 5% Isoflurane® in a carrier gas of 0.5 liter/minute oxygen and 1 liter/minute nitrous oxide to induce anaesthesia, reducing to 2% Isoflurane for maintenance anaesthesia. Administer 5mg/kg sub cutaneously (s.c.) Carprofen (Rimadyl® Large Animal Injection, 50 mg/ml, Pfizer Animal Health) at induction of anaesthesia, at end of day of surgery and on the morning of first day post-surgery to minimize pain and discomfort. Implantation of corpus cavernosal probe:- Shave the skin of the ventral abdomen and extend to include the area around the penis and ventral scrotum. Clean and disinfect the shaved area. Place the rat in dorsal recumbency. Make a mid-line incision from the external base of the penis, running caudally for approximately 2 cm. Locate and expose the internal structure of the penis and identify the corpus cavernosum. Make a mid-line laparotomy, approximately 4 cm in length to access the abdominal cavity. Pierce the abdominal wall via the caudal incision with a suitable trocar and cannula, taking care not to damage any internal organs. Place the implant body in the abdominal cavity with the catheter orientated caudally and pass the catheter tip through the body wall via the preplaced cannula. A model TA11 PA- C40, 8mm catheter implant may be used a with modified 3 mm tip (Data Sciences International Inc.). Secure the implant body to the abdominal wall using non-absorbable sutures and partially close the abdominal incision. Reflect the tip of the penis cranially and retract the caudal incision to optimize the surgical field. Carefully isolate approximately 10mm of the internal structure of the penis from the surrounding tissue. Carefully reflect the corpus spongiosum to one side to give access to the corpus cavernosum. Access the corpus cavernosum using a modified over-the-needle catheter to puncture the tunica. Introduce the catheter tip via the preplaced catheter and advance until fully inserted. Carefully remove the access catheter and apply a suitable tissue adhesive to the insertion site. Observe for leakage. Close the subcutaneous fat layer in the caudal incision before closing with an appropriate absorbable suture. Instil approximately 5 ml of warm saline through the abdominal incision and complete closure of the mid-line incision. Close the skin incision with an appropriate absorbable suture. Postoperative care:- Measure food and water intake and monitor bodyweight daily for at least 7 days post surgery, then 2-3 times weekly. Give Lectade® (Pfizer Animal Health) in drinking water for 3 days post surgery. House rats singly, and transfer to reverse light/ dark conditions 5 days post surgery. Named Veterinary Surgeon (or Deputy) to issue a certificate of fitness to continue 2 days post surgery. Start using rats experimentally 7 days post surgery. Experimental Procedure:- Perform experiment in room with reverse light/dark conditions. On day of experiment, place rat in home cage on receiver pad (PhysioTel® Model RPC-1 , Data Sciences International Inc.) and leave to acclimatize for approximately one hour. Ensure that the rat has food and water ad lib. Take baseline reading of intra cavernosal pressure (ICP) for approximately 5 minutes. Transfer the data via a floppy disk to an Excel spreadsheet. Inject the rat with compound subcutaneously or via the jugular vein catheter (JVC). If using the JVC, flush through with sterile saline after dosing and seal with a saline / glucose lock solution. The interval between administration of compound and ICP measurement will vary with the compound to be tested. An interval of 30-60 min post s.c. injection is a good guide. The test compounds are dissolved in 50% β-cyclodextrin in saline. They are administered at a dose of 5-10mg/kg subcutaneously (s.c). Apomorphine hydrochloride hemihydrate (Sigma™ A-4393) at 60 μg/kg s.c. is used as a positive control as it has pro-erectile properties. Record ICP over a 15 minute period, starting at 30 minutes post injection i.e. from 30 to 35 minutes and repeat for two further 15 minute periods commencing at 60 minutes post injection and 120 minutes post injection respectively. Record ICP for 15 minutes. A signal from the receiver pad feeds through to the Data Exchange Matrix® and hence to the software (Dataquest ART® acquisition system, Data Sciences International Inc.). Transfer the data via a floppy disk to an Excel spreadsheet for analysis. Combination with PDE5 inhibitor for treatment of MED The effects of concomitant administration of a compound of the present invention in combination with a PDE5 inhibitor (PDE5i) on the penile intracavernosal pressure (ICP) in an anaesthetised rabbit model of erection can be measured according to the following protocol. Experimental Protocol Male New Zealand rabbits (~2.5kg) are pre-medicated with a combination of Medetomidine (Domitor®) 0.5ml/kg inramuscularly (i.m.), and Ketamine (Vetalar®) 0.25ml/kg i.m. whilst maintaining oxygen intake via a face mask. The rabbits are tracheotomised using a Portex™ uncuffed endotracheal tube 3 ID (internal diameter), connected to ventilator and maintained at a ventilation rate of 30-40 breaths per minute, with an approximate tidal volume of 18-20 mi, and a maximum airway pressure of 10 cm H₂O. Anaesthesia is then switched to Isoflurane® and ventilation continued with O₂ at 2 litres/min. The right marginal ear vein is cannulated using a 23G or 24G catheter, and Lactated Ringer solution perfused at 0.5ml/min. The rabbit is maintained at 3% isoflurane during invasive surgery, dropping to 2% for maintenance anaesthesia. The left jugular vein is exposed, isolated and then cannulated with a PVC catheter (17 gauge / 17G) for the infusion of drugs and the test compounds. The left groin area of the rabbit is shaved and a vertical incision is made approximately 5cm in length along the thigh. The femoral vein and artery are exposed, isolated and then cannulated with a polyvinylchloride (PVC) catheter (17G) for the infusion of drugs and compounds. Cannulation is repeated for the femoral artery, inserting the catheter to a depth of 10 cm to ensure that the catheter reaches the abdominal aorta. This arterial catheter is linked to a Gould system to record blood pressure. Samples for blood gas analysis are also taken via the arterial catheter. Systolic and diastolic pressures are measured, and the mean arterial pressure calculated using the formula (diastolic x2 + systolic) ÷3. Heart rate is measured via the pulse oxymeter and a Po-ne-mah data acquisition software system (Ponemah Physiology Platform, Gould Instrument Systems Inc). A ventral midline incision is made into the abdominal cavity. The incision is about 5cm in length just above the pubis. The fat and muscle is bluntly dissected away to reveal the hypogastric nerve which runs down the body cavity. It is essential to keep close to the side curve of the pubis wall in order to avoid damaging the femoral vein and artery which lie above the pubis. The sciatic and pelvic nerves lie deeper and are located after further dissection on the dorsal side of the rabbit. Once the sciatic nerve is identified, the pelvic nerve is easily located. The term pelvic nerve is loosely applied; anatomy books on the subject fail to identify the nerves in sufficient detail. However, stimulation of the nerve causes an increase in intracavernosal pressure and cavemosal blood flow, and innervation of the pelvic region. The pelvic nerve is freed away from surrounding tissue and a Harvard bipolar stimulating electrode is placed around the nerve. The nerve is slightly lifted to give some tension, then the electrode is secured in position. Approximately 1 ml of light paraffin oil is placed around the nerve and electrode. This acts as a protective lubricant to the nerve and prevents blood contamination of the electrode. The electrode is connected to a Grass S88 Stimulator. The pelvic nerve is stimulated using the following parameters:- 5V, pulse width 0.5ms, duration of stimulus 20 seconds with a frequency of 16Hz. Reproducible responses are obtained when the nerve is stimulated every 15-20 minutes. Several stimulations using the above parameters are performed to establish a mean control response. The compound(s) to be tested are infused, via the jugular vein, using a Harvard 22 infusion pump allowing a continuous 15. minute stimulation cycle. The skin and connective tissue around the penis is removed to expose the penis. A catheter set (Insyte-W, Becton-Dickinson 20 Gauge 1.1 x 48mm) is inserted through the tunica albica into the left corpus cavemosal space and the needle removed, leaving a flexible catheter. This catheter is linked via a pressure transducer (Ohmeda 5299-04) to a Gould system to record intracavernosal pressure (ICP). Once an intracavernosal pressure is established, the catheter is sealed in place using Vetbond (tissue adhesive, 3M). Heart rate is measured via the pulse oxymeter and a Po-ne-mah data acquisition software system (Ponemah Physiology Platform, Gould Instrument Systems Inc). Intracavernosal blood flow is recorded either as numbers directly from the Flowmeter using Po- ne-mah data acquisition software (Ponemah Physiology Platform, Gould Instrument Systems Inc), or indirectly from Gould chart recorder trace. Calibration is set at the beginning of the experiment (0-125 ml/min/100g tissue). All data is reported as mean + s.e.m. (standard error of the mean). Significant changes are identified using Student's t-tests. The test compounds are dissolved in 50% β-cyclodextrin in saline. They are administered at a dose of 5-10mg/kg subcutaneously (s.c). Using the protocol described hereinbefore beneficial effects on ICP can be demonstrated for the concomitant administration of a compound of the present invention (5 -10 mg/kg s.c.) and a selective inhibitor of PDE5 (3-ethyl-5-{5-[4-ethylpiperzino)sulphonyl-2-propoxyphenyl}-2-(2-pyridylmethyl)-6,7- dihydro-2H-pyrazolo[4,3-d]pyrimidin-7-one (as described in WO98/491066) (1 mg/kg i.v.(intravenously)). A number of clinical benefits of concomitant administration of a PDE5 inhibitor and a compound of the present invention may be realized. Such benefits include increased efficacy and opportunities to treat MED subgroups that do not respond to other MED mono-therapies. Treatment of FSAD Serotonin 5HT₂c receptor agonists are known to potentiate pelvic nerve-stimulated increases in female genital blood flow in the anaesthetised rabbit model of sexual arousal. The normal sexual arousal response consists of a number of physiological responses that are observed during sexual excitement. These changes such as vaginal, labial and clitoral engorgement result from increases in genital blood flow. Engorgement leads to increased vaginal lubrication via plasma transudation, increased vaginal compliance (relaxation of vaginal smooth muscle) and increases in vaginal and clitoral sensitivity. Female sexual arousal disorder (FSAD) is a highly prevalent sexual disorder affecting up to 40% of pre-, peri- and postmenopausal (±HRT) women. The primary consequence of FSAD is reduced genital engorgement or swelling which manifests itself as a lack of vaginal lubrication and a lack of pleasurable genital sensation. Secondary consequences include reduced sexual desire, pain during intercourse and difficulty in achieving orgasm. The most common cause of FSAD is decreased genital blood flow resulting in reduced vaginal, labial and clitoral engorgement (Berman, J., Goldstein, I., Werbin, T. et al. (1999a). Double blind placebo controlled study with crossover to assess effect of sildenafil on physiological parameters of the female sexual response. J. Urol., 161 , 805; Goldstein, I. & Berman, J. R. (1998). Vasculogenic female sexual dysfunction: vaginal engorgement and clitoral erectile insufficiency syndromes. Int. J. Impot. Res., 10, S84-S90; Park, K., Goldstein, I., Andry, C, et al. (1997). Vasculogenic female sexual dysfunction: The hemodynamic basis for vaginal engorgement insufficiency and clitoral erectile insufficiency. Int. J. Impotence Res., 9, 27-37; Werbin, T., Salimpour, P., Berman, L., et al. (1999). Effect of sexual stimulation and age on genital blood flow in women with sexual stimulation. J. Urol., 161 , 688). As explained herein, the present invention provides a means for restoring or potentiating the normal sexual arousal response in women suffering from FSAD, by enhancing genital blood flow. The following describes a method for testing such response. FSAD Method Female New Zealand rabbits (-2.5kg) are pre-medicated with a combination of Medetomidine (Domitor®) 0.5ml/kg intramuscularly (i.m.), and Ketamine (Vetalar®) 0.25ml/kg i.m. while maintaining oxygen intake via a face mask. The rabbits are tracheotomised using a Portex™ uncuffed endotracheal tube 3 ID (internal diameter), connected to ventilator and maintained at a ventilation rate of 30-40 breaths per minute, with an approximate tidal volume of 18-20 ml, and a maximum airway pressure of 10 cm H₂O. Anaesthesia is then switched to Isoflurane® and ventilation continued with O₂ at 2 l/min. The right marginal ear vein is cannulated using a 23G or 24G catheter, and Lactated Ringer solution perfused at 0.5 ml/min. The rabbit is maintained at 3% Isoflurane® during invasive surgery, dropping to 2% for maintenance anaesthesia. The left groin area of the rabbit is shaved and a vertical incision is made approximately 5 cm in length along the thigh. The femoral vein and artery are exposed, isolated and then cannulated with a PVC catheter (17G) for the infusion of drugs and compounds. Cannulation is repeated for the femoral artery, inserting the catheter to a depth of 10cm to ensure that the catheter has reached the abdominal aorta. This arterial catheter is linked to a Gould system to record blood pressure. Samples for blood gas analysis are also taken via the arterial catheter. Systolic and diastolic pressures are measured, and the mean arterial pressure calculated using the formula (diastolic x2 + systolic) ÷3. Heart rate is measured via the pulse oxymeter and Po-ne-mah data acquisition software system (Ponemah Physiology Platform, Gould Instrument Systems Inc). A ventral midline incision is made into the abdominal cavity. The incision is about 5cm in length just above the pubis. The fat and muscle is bluntly dissected away to reveal the hypogastric nerve which runs down the body cavity. It is essential to keep close to the side curve of the pubis wall in order to avoid damaging the femoral vein and artery, which lie above the pubis. The sciatic and pelvic nerves lie deeper and are located after further dissection on the dorsal side of the rabbit. Once the sciatic nerve is identified, the pelvic nerve is easily located. The term pelvic nerve is loosely applied; anatomy books on the subject fail to identify the nerves in sufficient detail. However, stimulation of the nerve causes an increase in vaginal and clitoral blood flow, and innervation of the pelvic region. The pelvic nerve is freed away from surrounding tissue and a Harvard bipolar stimulating electrode is placed around the nerve. The nerve is slightly lifted to give some tension, then the electrode is secured in position. Approximately 1 ml of light paraffin oil is placed around the nerve and electrode. This acts as a protective lubricant to the nerve and prevents blood contamination of the electrode. The electrode is connected to a Grass S88 Stimulator. The pelvic nerve is stimulated using the following parameters:- 5V pulse width 0.5 ms, duration of stimulus 10 seconds and a frequency range of 2 to 16 Hz. Reproducible responses are obtained when the nerve is stimulated every 15-20 minutes. A frequency response curve is determined at the start of each experiment in order to determine the optimum frequency to use as a sub-maximal response, normally 4 Hz. A ventral midline incision is made, at the caudal end of the pubis, to expose the pubic area. Connective tissue is removed to expose the tunica of the clitoris, ensuring that the wall is free from small blood vessels. The external vaginal wall is also exposed by removing any connective tissue. One laser Doppler flow probe is inserted 3cm into the vagina, so that half the probe shaft is still visible. A second probe is positioned so that it lay just above the external clitoral wall. The position of these probes is then adjusted until a signal is obtained. A second probe is placed just above the surface of a blood vessel on the external vaginal wall. Both probes are clamped in position. Vaginal and clitoral blood flow is recorded either as numbers directly from the Flowmeter using Po-ne-mah data acquisition software (Ponemah Physiology Platform, Gould Instrument Systems Inc), or indirectly from Gould chart recorder trace. Calibration is set at the beginning of the experiment (0- 125ml/min/100g tissue). All data are reported as mean + standard error of the mean (s.e.m.). Significant changes are identified using Student's t-tests.

Claims

CLAIMS What is claimed is: 1. A compound of Formula (I)

(I) wherein; R^1a is hydrogen or (C_rC₄)alkyl, or R^1a taken together with R^1b forms a 5- to 10-membered partially or fully saturated heterocyclic ring containing one to two additional N atoms, where said heterocyclic ring is optionally substituted with one or more independently selected from the group consisting of fluoro, (CrC₄)alkyl, fluoro-substituted (C_rC₄)alkyl, and fluoro-substituted(C₁-C₄)alkoxy; R^1b is (i) hydrogen, (ii) a partially or fully saturated 3- to 6-membered carbocyclic ring, (iii) a partially or fully saturated 4- to 8-membered heterocyclic ring containing one to two heteroatoms selected from O, N or S, or (iv) a (C₁-C₈)alkyl optionally substituted with one or more substituents independently selected from the group consisting of an optionally substituted phenyl, an optionally substituted 5- to 6-membered heteroaryl, (C₁-C₆)alkylamino, di(CrC₆)alkylamino, 3- to 8-membered partially or fully saturated carbocyclic ring, and 4- to 7-membered partially or fully saturated heterocyclic ring containing one to three heteroatoms independently selected from O, N and S, provided that R^1b is not a (Ci-C₆)alkyl substituted with a group selected from phenyl, an optionally substituted pyridyl, or an optionally substituted thiophene; n is 1 , 2 or 3; R² is hydrogen; R³ is (i) hydrogen, (ii) a (CrCβJalkyl optionally substituted with one or more substituents independently selected from the group consisting of (CrC₆)alkoxy, halo, fluoro-substituted (C₁- C₄)alkyl, fluoro-substituted(CrC₄)alkoxy, amino, (C₁-C₆) alkylamino, di(C_r C₆)alkylamino, 3- to 8-membered partially or fully saturated carbocyclic ring, and 3- to 8-membered heterocyclic ring containing 1 to 2 heteroatoms independently selected from O, N or S, (iii) a 3- to 8-membered partially or fully saturated carbocyclic ring, (iv) a 5- to 6-membered heteroaryl containing 1 to 2 heteroaroms independently selected from O, N or S, a 4- to 8-membered heterocyclic ring containing 1 to 2 heteroatoms independently selected from O, N or S, or (v) a phenyl group optionally substituted with one or more substitutents independently selected from the group consisting of halo, (CrC₆)alkyl, fluoro-substituted (C_rC₄)alkyl, (Ci-C₄)alkoxy, and fluoro-substituted(C_rC₄)alkoxy; R⁴ and R⁵ are each independently hydrogen, or (C_rC₆)alkyl; R⁶, R⁷, R⁸ and R⁹ are each independently selected from the group consisting of hydrogen, (C₁- C₈)alkyl, (C_rC₈)alkyl-R¹¹, fluoro-substituted (Ci-C₄)alkyl, cyano, halo, -NHC(O)-(C_rC₄)alkyl, (C₁- C₆)alkoxy, fluoro-substituted (CrC₄)alkoxy, aryloxy, heteroaryloxy, a 3- to 8-membered partially or fully saturated carbocyclic ring, a 4- to 8-membered heterocyclic ring containing 1 to 2 heteroatoms independently selected from O, N or S, a phenyl substituted with one or more substituents independently selected from R¹¹, or a 5- to 10-membered heteroaryl containing 1 to 3 heteroatoms independently selected from O, S or N, where said aryloxy, said heteroaryl and said heteroaryloxy are optionally substituted with one or more substituents independently selected from R¹¹, provided that at least one of R⁶, R⁷, R⁸ and R⁹ is other than hydrogen, or R⁸ and R⁹ taken together form a partially or fully saturated 5- to 9-membered carbocyclic ring or a 4- to 8-membered heterocyclic ring containing 1 to 3 heteroatoms independently selected from O, N and S, or R⁸ and R⁹ taken together form a fused 6-membered aromatic ring or a fused 5- to 6-membered heteroaromatic ring containing 1 to 2 heteroatoms selected from O, N or S; R¹⁰ is (C₃-C₆)cycloalkyl, or 4- to 8-membered partially or fully saturated heterocycle containing 1 to 3 heteroatoms selected from O, N or S aryl, or heteroaryl containing 1 to 3 heteroatoms selected from O, N or S; R¹¹ is halo, cyano, (Ci-C₆)alkyl, fluoro-substituted (C₁-C₄)alkyl, fluoro-susbsituted (C_rC₄)alkoxy, aryl, heteroaryl,

di(C₁-C₆)alkylamino(C₁-C₆)alkyl, acyl, acylamino, aminoacyl, (CrC^alkylaminoacyl, di(C₁-C₆)alkylaminoacyl, (Ci-C₆)alkylsulfonamido, arylsulfonamido, - 0R^11a, -SR^11a, -SOR^11a, or -SO₂R^11a, where R^11a is (C_rC₆)alkyl, -CF₃, a 3- to 8-membered fully saturated carbocyclic ring, or 4- to 10-membered partially or fully saturated heterocyclic ring containing 1 to 3 heteroatoms selected from O, N or S, a pharmaceutically acceptable salt thereof, a prodrug of the compound or the salt, or a solvate or hydrate of the compound, the prodrug, or the salt.

2. The compound of Claim 1 wherein R^1a is hydrogen or (C_rC₄)alkyl; and R^1b is (i) hydrogen, (ii) a fully saturated 3 to 6-membered carbocyclic ring, (iii) a fully saturated 4 to 8-membered heterocyclic ring containing one to two N atoms, or (iv) a (CrCβJalkyl optionally substituted with one or more substituents independently selected from the group consisting of (C₁-C₄)alkylamino, 3 to 6-membered fully saturated carbocyclic ring, and 4 to 8-membered fully saturated heterocyclic ring containing a N atom; a pharmaceutically acceptable salt of said compound, or a solvate or hydrate of said compound or said salt.

3. The compound of Claim 2 wherein R^1a is hydrogen or (C_rC₄)alkyl; and R^1b is hydrogen, (CrC₄)alkyl, or a 3 to 4-membered fully saturated carbocyclic ring; a pharmaceutically acceptable salt of said compound, or a solvate or hydrate of said compound or said salt.

4. The compound of Claim 1 wherein R^1a taken together with R^1b forms a 5- to 10- membered partially or fully saturated heterocyclic ring containing one to two additional N atoms, where said heterocyclic ring is optionally substituted with one or more independently selected fluoro, (C₁- C₄)alkyl, fluoro-substituted (C_rC₄)alkyl, and fluoro-substituted(C₁-C₄)alkoxy; a pharmaceutically acceptable salt of said compound, or a solvate or hydrate of said compound or said salt.

5. The compound of Claim 1 , 2, 3, or 4 wherein n is 1 or 2; and R⁴ and R⁵ are both hydrogen; a pharmaceutically acceptable salt of said compound, or a solvate or hydrate of said compound or said salt.

6. The compound of Claim 5 where n is 1 ; a pharmaceutically acceptable salt of said compound, or a solvate or hydrate of said compound or said salt.

7. The compound of Claim 6 wherein R⁶, R⁷, R⁸, R⁹ are each independently selected from the group consisting of hydrogen, (C_rC₆)alkyl, fluoro-substituted (CrC₄)alkyl, cyano, halo, (Ci-C₆)alkoxy, fluoro-substituted (C_rC₄)alkoxy. aryloxy, a 3- to 8-membered fully saturated carbocyclic ring, a fully saturated 4- to 8-membered heterocyclic ring, a phenyl substituted with one to three substituents independently selected from R¹¹, a 5-10-membered heteroaryl containing 1 to 3 heteroatoms independently selected from O, S, or N where said aryloxy and said heteroaryl is optionally substituted with one or more substituents selected from the group consisting of halo, cyano, (C_rC₆)alkyl, fluoro-substituted (CrC₄)alkyl, fluoro-substituted (C₁-C₄)alkoxy, acylamino, and aminoacyl, or R⁸ and R⁹ taken together form a partially or fully saturated 5- to 6- membered carbocyclic ring or a 4- to 8-membered partially or fully saturated heterocyclic ring containing 1-3 heteroatoms independently selected from O, N, or S; a pharmaceutically acceptable salt of said compound, or a solvate or hydrate of said compound or said salt.

8. A pharmaceutical composition comprising (a) a compound of any one of the preceding claims, a pharmaceutically acceptable salt thereof or a solvate or hydrate of said compound or said salt; and (b) a pharmaceutically acceptable excipient, diluent, or carrier 9. A method for treating a 5-HT₂ receptor-mediated disease, condition, or disorder in an animal comprising the step of administering to said animal a therapeutically effective amount of a compound of Claim 1 , a pharmaceutically acceptable salt thereof, or a solvate or hydrate of said compound or said salt. 10. The use of a compound of Claim 1 in the manufacture of a medicament for treating a 5- HT₂ receptor-mediated disease, condition, or disorder selected from obesity, controlling weight gain, psychoisis, female sexual dysfunction, or male erectile dysfunction.