9-AMINO-1,2,3,4-TETRAHYDROACRIDIN-1-OL AND RELATED COMPOUNDS, A PROCESS FOR THEIR PREPARATION AND THEIR USE AS MEDICAMENTS

Abstract: There are disclosed compounds having the formula for wherein n is 1, 2 or 3; X is hydrogen, loweralkyl, loweralkoxy, halogen, hydroxy, nitro, trifluoromethyl, NHCOR₂ where R₂ is loweralkyl, or NR₃R₄ where R₃ and R₄ are independently hydrogen or loweralkyl; R is hydrogen or loweralkyl; R₁ is hydrogen, loweralkyl, diloweralkylaminoloweralkyl, aryl­ loweralkyl, diarylloweralkyl, furylloweralkyl, thienylloweral­ kyl, oxygen-bridged arylloweralkyl, oxygen-bridged diaryl­ loweralkyl, oxygen-bridged furylloweralkyl or oxygen-­ bridged thienylloweralkyl; Y is C=O or CR₅OH where R₅ is hydrogen or loweralkyl; Z is CH₂ or C=CR₆R₇ where R₆ and R₇ are independently hydrogen or loweralkyl; or Y and Z taken together is CR₅=CH where CR₅ and CH correspond to Y and Z respectively; an optical antipode thereof, or a phar­ maceutically acceptable acid addition salt thereof, which are useful for enhancing memory, methods for synthesizing them, and pharmaceutical compositions comprising an effective memory enhancing amount of such a compound.

Description: This invention relates to compounds having the formula wherein n is 1, 2 or 3; X is hydrogen, C₁-C₆-alkyl, C₁-C₆-alkoxy, halogen, hydroxy ,nitro, trifluoromethyl, NHCOR₂ where R₂ is C₁-C₆-alkyl, or NR₃R₄ where R₃ and R₄ are independently hydrogen or C₁-C₆-alkyl; R is hydrogen or C₁-C₆-alkyl; R₁ is hydrogen, C₁-C₆-alkyl, di-C₁-C₆-alkyl-amino-C₁-C₆-alkyl, phenyl-C₁-C₆-alkyl, diphenyl-C₁-C₆-alkyl, phenyloxy-C₁-C₆-alkyl or di(phenyl)-methoxy-C₁-C₆-alkyl, wherein the phenyl group is unsubstituted or has 1, 2 or 3 substituents each of which being independently C₁-C₆-alkyl, C₁-C₆-alkoxy, halogen, hydroxy, CF₃, phenoxy or benzyloxy, or the phenyl group is substituted with four or five fluorine, chlorine or bromine atoms, or R₁ is furyl-C₁-C₆-alkyl, furyloxy-C₁-C₆-alkyl, thienyl-C₁-C₆-alkyl or thienyloxy-C₁-C₆-alkyl, Y is C=O or CR₅OH where R₅ is hydrogen or C₁-C₆-alkyl; Z is CH₂ or C=CR₆R₇ where R₆ and R₇ are independently hydrogen or C₁-C₆-alkyl; or Y and Z taken together is CR₅=CH where CR₅ and CH correspond to Y and Z respectively; an optical antipode thereof, or a pharmaceutically acceptable acid addition salt thereof. which are useful for enhancing memory, methods For synthesizing them, and pharmaceutical compositions comprising an effective memory enhancing amount of such a compound. This invention also relates to compounds having the formula where X and n are as defined above which are useful as intermediate compounds for synthesizing the compounds of Formula I and a method for synthesizing them. Throughout the specification and the appended claims, a given chemical formula or name shall encompass all stereo and optical isomers thereof where such isomers exist, as well as pharmaceutically acceptable acid addition salts thereof and solvates thereof such as for instance hydrates. The following definitions shall apply throughout the specification and the appended claims. Unless otherwise stated or indicated, the term C₁-C₆-alkyl denotes a straight or branched alkyl group having from 1 to 6 carbon atoms. Examples include methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl and straight- and branched-chain pentyl and hexyl. Unless otherwise stated or indicated, the term C₁-C₆-alkoxy denotes a straight or branched alkoxy group having from 1 to 6 carbon atoms. Examples include methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, sec-butoxy, t-butoxy and straight- and branched-chain pentoxy and hexoxy. The compounds of this invention are prepared by utilizing one or more of the steps described below not necessarily in the order presented. In order to simplify the description of the synthetic schemes, the description will be presented with specific reference to the situation where n is 2, but it will readily be understood that the synthetic schemes can also be applied to the other situations where n is 1 or 3 by making obvious modifications where necessary. Throughout the description of the synthetic steps, definitions of X, Y, Z, R and R₁ through R₇ are as given above unless otherwise stated or indicated. STEP A Compounds of Formula II are prepared by reacting a compound of Formula III with 1,3-cyclohexadione. Typically, said reaction is conducted in a suitable solvent such as tetrahydrofuran, diethyl ether, diethylene glycol dimethyl ether, dioxane, benzene or toluene at a temperature of about 3⊘-12⊘°C. STEP B Compounds of Formula IV are prepared by cyclizing compound IIa in the presence of a metallic halide such as cuprous chloride, cuprous bromide or cuprous iodide used as a catalyst. Typically said cyclization reaction is conducted in a suitable solvent such as an ethereal solvent including tetrahydrofuran, diethyl ether and dioxane and in the presence of a catalyst and a basic inorganic salt such as potassium carbonate, potassium bicarbonate, sodium carbonate or sodium bicarbonate at a temperature of about 3⊘-1⊘⊘°C. STEP C Compounds of Formula V (where R₁ is not hydrogen and X is not OH, NHCOR₂, amino or C₁-C₆-alkylamino) are prepared by reacting compound IV with a compound of the formula R₁W, W being Cl, Br, I or OSO₃CH₃ (mesyloxy). Typically, said reaction is conducted in a biphasic system comprising a suitable organic solvent such as dichloromethane, chloroform, benzene or toluene, a strongly alkaline aqueous phase such as 5⊘% aqueous NaOH, the starting compounds and a phase transfer catalyst such as tetrabutylammonium hydrogen sulfate at a temperature of about ⊘-5⊘°C. Where X is OH, the excluded compounds can be prepared by subjecting a compound of Formula V where X is a C₁-C₆-alkoxy group (e.g. methoxy group) to a cleavage reaction conducted, for instance, with the aid of pyridine hydrochloride at a temperature of around 18⊘°C. Where X is amino, the excluded compounds can be prepared from compound V where X is nitro by hydrogenating it in the manner described below as STEP F. Where X is NHCOR₂, the excluded compounds can be obtained by subjecting the corresponding amino compounds (X=NH₂) obtained above to an acylation reaction using, for instance, (R₂CO)₂O in substantially the same manner as described below as STEP G. Where X is C₁-C₆-alkylamino, the excluded compounds can be prepared by reacting the corresponding acylamino compounds (X=NHCOR₂) obtained above with a C₁-C₆-alkyl iodide or bromide of the formula R₃I or R₃Br where R₃ is C₁-C₆-alkyl in the presence of an inorganic base such as KOH or the like, and hydrolyzing the resultant product where X is in a routine manner. STEP D In a manner similar to the one described above as STEP C, compounds of Formula VI (where neither of R₁ and R is hydrogen and X is not OH, NHCOR₂, amino or C₁-C₆-alkylamino) are obtained by further reacting compound V with a compound RW, W being the same as defined above. Where X is OH, NHCOR₂, amino or C₁-C₆-alkylamino, the excluded compounds can be obtained by use of the reaction schemes described above in STEP C for preparing compounds V where X is OH, NHCOR₂, amino or C₁-C₆-alkylamino, respectively. STEP E Compounds of Formula VII where R₁ is hydrogen or C₁-C₆-alkyl may be prepared by the nitration of a compound of Formula VIII. Said nitration occurs with a good selectivity at the 7-position of the ring. Said reaction is typically conducted in the presence of concentrated sulfuric acid and nitric acid at a temperature of from about -1⊘° to about 3⊘°C. STEP F Compounds of Formula IX are prepared by the hydrogenation of compound VII in the presence of hydrogen gas and a suitable catalyst such as for instance a noble metal including palladium, platinum or rhodium. Typically, said hydrogenation is conducted in a suitable medium such as glacial acetic acid or ethanol under a suitable hydrogen gas pressure such as about 0.7-4.1 bar (10-60 pounds per square inch) gauge at a temperature of about 2⊘-4⊘°C. STEP G Compounds of Formula X are prepared by reacting compound IX with a suitable acylating agent such as an acid anhydride of the formula (R₂CO)₂O in a suitable solvent such as a carboxylic acid of the formula R₂COOH. Typically said reaction is conducted at a temperature of about 8⊘-12⊘°C. STEP H Compounds of Formula XI (where X is not NHCOR₂ or NO₂) are prepared by reacting a compound of Formula XII obtained from one of the foregoing STEPS A through G with a suitable metal hydride such as LiAlH₄ in a suitable solvent such as an ethereal solvent including tetrahydrofuran, diethyl ether, dioxane and mixtures thereof at a temperature of from about -2⊘° to about 2⊘°C, and thereafter hydrolyzing the product. Where X is NO₂, the excluded compounds can be prepared by reducing compounds XII where X is NO₂ with NaBH₄ in a suitable medium such as acetic acid, hydrochloric acid or phosphoric acid aqueous solution. STEP I Compounds of Formula XIII (where X is not NHCOR₂) are prepared by reacting compound XII with a suitable organometallic compound such as a compound of the formula R₅Li (where R₅ is C₁-C₆-alkyl) in a suitable solvent such as an ethereal solvent including tetrahydrofuran, diethyl ether and dioxane at a temperature of about 1⊘-5⊘°C. Subsequent to the reaction of compound XII with R₅Li, the resultant product is hydrolyzed to obtain compound XIII. Where X is NHCOR₂ in the above STEPS H or I, the excluded compounds can be prepared in general by use of the above reaction STEPS A through I in a different sequence. For example, compounds of Formula XI-a below can be prepared by use of the sequence depicted below. STEP J Compounds of Formula XIV are prepared by first reacting compound XII with a compound of Formula XV to obtain an intermediate compound of Formula XVI and then converting the latter to compound XIV. The first reaction is conducted typically in a suitable medium such as trifluoroacetic acid, acetic anhydride or an alcohol plus hydrochloric acid at a temperature of about 7⊘-12⊘°C. The second reaction is conducted typically in a suitable solvent such as toluene or benzene at a temperature of about 8⊘-12⊘°C. STEP K Compounds of Formula XVII are prepared by the dehydration rection of compound XI or XIII obtained from STEP H or I above. Typically, said dehydration is conducted in the presence of a suitable solvent such as glacial acetic acid, dimethylformamide or dimethyl sulfoxide and a small amount of acid such as sulfuric acid at a temperature of about 7⊘-12⊘°C. STEP L Compounds of Formula XVIII (where X is not NHCOR₂ or NO₂ and R₅ is H or C₁-C₆-alkyl) may be prepared by reacting compound XIV with (i-Bu)₂AlH or R₅li (R₅ is C₁-C₆-alkyl) in the same manner as described in STEP H or I, respectively: Although the foregoing reaction steps are directed to the situation where n is 2, it will be understood that other compounds of this invention where n is 1 or 3 can be prepared by making obvious modifications in the above reaction steps where necessary. Thus, for instance, compounds of formula IIb can be obtained from compound III and 1,3-cyclopentadione in substantially the same manner as STEP A, and compounds of formula XXIX can be obtained by cyclizing said compound IIb in substantially the same manner as STEP B. Similarly, compounds of formula IIc can be obtained from compound III and 1,3-cycloheptadione in substantially the same manner as STEP A, and compounds of formula XXX can be obtained by cyclizing said compound IIc in substantially the same manner as STEP B. The compounds of formula (I) of the present invention are useful in the treatment of various memory dysfunctions characterized by decreased cholinergic function, such as Alzheimer's disease. This utility is manifested by the ability of these compounds to inhibit the enzyme cholinesterase and thereby increase acetylcholine levels in the brain. Additionally, some of the compounds of this invention exhibit antidepressant activities, which activities being particularly helpful for patients suffering from Alzheimer's disease. Further, the compounds of this invention are in general less toxic and have a broader therapeutic window than heretofore known compounds such as tacrine and physostigmine, making them more therapeutically acceptable. Cholinesterase Inhibition Assay The ability to inhibit acetylcholinesterase was determined by the photometric method of Ellman et al., Biochem. Pharmacol. 7 , 88 (1961). This utility is further demonstrated by the ability of these compounds to restore cholinergically deficient memory in the Dark Avoidance Assay, where they are in general active over a broader dose range than heretofore known compounds, a distinct therapeutic advantage. Dark Avoidance Assay In this assay mice are tested for their ability to remember an unpleasant stimulus for a period of 24 hours. A mouse is placed in a chamber that contains a dark compartment; a strong incandescent light drives it to the dark compartment, where an electric shock is administered through metal plates on the floor. The animal is removed from the testing apparatus and tested again, 24 hours later, for the ability to remember the electric shock. If scopolamine, an anticholinergic that is known to cause memory impairment, is administered before an animal's initial exposure to the test chamber, the animal re-enters the dark compartment shortly after being placed in the test chamber 24 hours later. This effect of scopolamine is blocked by an active test compound, resulting in a greater interval before re-entry into the dark compartment. The results for an active compound are expressed as the percent of a group of animals in which the effect of scopolamine is blocked, as manifested by an increased interval between being placed in the test chamber and re-entering the dark compartment. Effective quantities of the compounds of the invention may be administered to a patient by any of the various methods, for example, orally as in capsules or tablets, parenterally in the form of sterile solutions or suspensions, and in some cases intravenously in the form of sterile solutions. The free base final products, while effective themselves, may be formulated and administered in the form of their pharmaceutically acceptable acid addition salts for purposes of stability, convenience of crystallization, increased solubility and the like. Acids useful for preparing the pharmaceutically acceptable acid addition salts of the invention include inorganic acids such as hydrochloric, hydrobromic, sulfuric, nitric, phosphoric and perchloric acids, as well as organic acids such as tartaric, citric, acetic, succinic, maleic, fumaric and oxalic acids. The active compounds of the present invention may be orally administered, for example, with an inert diluent or with an edible carrier, or they may be enclosed in gelatin capsules, or they may be compressed into tablets. For the purpose of oral therapeutic administration, the active compounds of the invention may be incorporated with excipients and used in the form of tablets, troches, capsules, elixirs, suspensions, syrups, wafers or chewing gum. These preparations should contain at least ⊘.5% of active compound, but may be varied depending upon the particular form and may conveniently be between 4% to about 7⊘% of the weight of the unit. The amount of active compound in such compositions is such that a suitable dosage will be obtained. Preferred compositions and preparations according to the present invention are prepared so that an oral dosage unit form contains between 1.⊘-3⊘⊘ milligrams of active compound. The tablets, pills, capsules or troches may also contain the following ingredients: a binder such as micro-crystalline cellulose, gum tragacanth or gelatin; an excipient such as starch or lactose, a disintegrating agent such as alginic acid or cornstarch; a lubricant such as magnesium stearate; a glidant such as colloidal silicon dioxide; and a sweetening agent such as sucrose or saccharin may be added or a flavoring agent such as peppermint, methyl salicylate, or orange flavoring. When the dosage unit form is a capsule, it may contain, in addition to materials of the above type, a liquid carrier such as a fatty oil. Other dosage unit forms may contain other various materials which modify the physical form of the dosage unit, for example, as coatings. Thus tablets or pills may be coated with sugar, shellac, or other enteric coating agents. A syrup may contain, in addition to the active compounds, sucrose as a sweetening agent and certain preservatives, dyes, coloring and flavors. Materials used in preparing these various compositions should be pharmaceutically pure and non-toxic in the amounts used. For the purposes of parenteral therapeutic administration, the active compounds of the invention may be incorporated into a solution or suspension. These preparations should contain at least ⊘.1% of active compound, but may be varied between ⊘.5 and about 3⊘% of the weight thereof. The amount of active compound in such compositions is such that a suitable dosage will be obtained. Preferred compositions and preparations according to the present invention are prepared so that a parenteral dosage unit contains between ⊘.5 to 1⊘⊘ milligrams of active compound. The solutions or suspension may also include the following components: a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid; buffers such as acetates, citrates or phosphates and agents for the adjustment of tonicity such as sodium chloride or dextrose. The parenteral preparation can be enclosed in disposable syringes or multiple dose vials made of glass or plastic. Examples of the compounds of this invention include: 9-Amino-3,4-dihydroacridin-1(2H)-one; 9-Amino-3,4-dihydro-6-methylacridin-1(2H)-one; 9-Amino-3,4-dihydro-6-methoxyacridin-1(2H)-one; 9-Amino-3,4-dihydro-6-fluoroacridin-1(2H)-one; 9-Amino-6-chloro-3,4-dihydroacridin-1(2H)-one; 9-Amino-7-chloro-3,4-dihydroacridin-1(2H)-one; 9-Amino-3,4-dihydro-6-trifluoromethylacridin-1(2H)-one; 9-Amino-3,4-dihydro-7-nitroacridin-1(2H)-one; 7,9-Diamino-3,4-dihydroacridin-1(2H)-one; N-[9-Amino-3,4-dihydro-1(2H)-oxoacridin-7-yl]acetamide; 3,4-Dihydro-9-methylaminoacridin-1(2H)-one; 3-4-Dihydro-9-methylamino-7-nitroacridin-1(2H)-one; 3,4-Dihydro-9-propylaminoacridin-1(2H)-one; 3,4-Dihydro-9-[2-(dimethylamino)ethyl]aminoacridin-1(2H)-one; 9-Benzylamino-3,4-dihydroacridin-1(2H)-one; 9-Benzylamino-3,4-dihydro-6-methylacridin-1(2H)-one; 9-Benzylamino-3,4-dihydro-6-fluoroacridin-1(2H)-one; 9-Benzylamino-6-chloro-3,4-dihydroacridin-1(2H)-one; 9-Benzylamino-3,4-dihydro-6-trifluoromethylacridin-1(2H)-one; 3,4-Dihydro-9-(2-methylbenzylamino)acridin-1(2H)-one; 3,4-Dihydro-9-(3-methylbenzylamino)acridin-1(2H)-one; 3,4-Dihydro-9-(4-methylbenzylamino)acridin-1(2H)-one; 3,4-Dihydro-9-(2-methoxybenzylamino)acridin-1(2H)-one; 3,4-Dihydro-9-(3-methoxybenzylamino)acridin-1(2H)-one; 3,4-Dihydro-9-(4-methoxybenzylamino)acridin-1(2H)-one; 3,4-Dihydro-9(2-fluorobenzylamino)acridin-1(2H)-one; 3,4-Dihydro-9-(3-fluorobenzylamino)acridin-1(2H)-one; 3,4-Dihydro-9-(4-fluorobenzylamino)acridin-1(2H)-one; 6-Chloro-3,4-dihydro-9-(4-fluorobenzylamino)acridin-1(2H)-one; 9-(2-Chlorobenzylamino)-3,4-dihydroacridin-1(2H)-one; 9-(3-Chlorobenzylamino)-3,4-dihydroacridin-1(2H)-one; 9-(4-Chlorobenzylamino)-3,4-dihydroacridin-1(2H)-one; 3,4-Dihydro-9-[(2,3,4,5,6-pentafluorobenzyl)amino]acridin-1(2H)-one; 3,4-Dihydro-9-(2-trifluoromethylbenzylamino)acridin-1(2H)-one; 3,4-Dihydro-6-fluoro-9-(2-trifluoromethylbenzylamino)-acridin-1(2H)-one; 3,4-Dihydro-9-(3-trifluoromethylbenzylamino)acridin-1(2H)-one; 3,4-Dihydro-9-(4-trifluoromethylbenzylamino)acridin-1(2H)-one; 3,4-Dihydro-9-phenethylaminoacridin-1(2H)-one; 3,4-Dihydro-9-(4,4-diphenylbutyl)aminoacridin-1(2H)-one; 3,4-Dihydro-9-(4,4-diphenylbutylamino)-6-trifluoromethylacridin-1(2H)-one; 9-[4,4-Bis(3-fluorophenyl)butylamino]-3,4-dihydroacridin-1(2H)-one; 9-[4,4-bis(4-fluorophenyl)butylamino]-3,4-Dihydroacridin-1(2H)-one; 3,4-Dihydro-9-(3-phenoxypropylamino)acridin-1(2H)-one; 9-[2-[Bis(4-fluorophenyl)methoxy]ethylamino-3,4-dihydroacridin-1(2H)-one; 9-[4-(Benzyloxy)benzylamino]-3,4-dihydroacridin-1(2H)-one; 3,4-Dihydro-9-[(2-thienyl)methylamino]acridin-1(2H)-one; 9-Amino-2,3-dihydro-cyclopenta[b]quinolin-1-one; 9-Amino-1,2,3,4-tetrahydroacridin-1-ol; 9-Amino-6-chloro-1,2,3,4-tetrahydroacridin-1-ol; 9-Amino-7-chloro-1,2,3,4-tetrahydroacridin-1-ol; 9-Amino-6-methoxy-1,2,3,4-tetrahydroacridin-1-ol; 9-Amino-6-fluoro-1,2,3,4-tetrahydroacridin-1-ol; 9-Amino-1,2,3,4-tetrahydro-6-trifluoromethylacridin-1-ol; 9-Methylamino-1,2,3,4-tetrahydroacridin-1-ol; 9-Propylamino-1,2,3,4-tetrahydroacridin-1-ol; 9-[2-(Dimethylamino)ethyl]amino-1,2,3,4-tetrahydroacridin-1-ol; 9-Benzylamino-1,2,3,4-tetrahydroacridin-1-ol; 9-Benzylamino-6-methyl-1,2,3,4-tetrahydroacridin-1-ol; 9-Benzylamino-6-fluoro-1,2,3,4-tetrahydroacridin-1-ol; 9-Benzylamino-6-chloro-1,2,3,4-tetrahydroacridin-1-ol; 9-Benzylamino-1,2,3,4-tetrahydro-6-trifluoromethylacridin-1-ol; 9-(2-Methylbenzylamino)-1,2,3,4-tetrahydroacridin-1-ol; 9-(3-Methylbenzylamino)-1,2,3,4-tetrahydroacridin-1-ol; 9-(4-Methylbenzylamino)-1,2,3,4-tetrahydroacridin-1-ol; 9-(2-Methoxybenzylamino)-1,2,3,4-tetrahydroacridin-1-ol; 9-(3-Methoxybenzylamino)-1,2,3,4-tetrahydroacridin-1-ol; 9-(4-Methoxybenzylamino)-1,2,3,4-tetrahydroacridin-1-ol; 9-(2-Fluorobenzylamino)-1,2,3,4-tetrahydroacridin-1-ol; 9-(3-Fluorobenzylamino)-1,2,3,4-tetrahydroacridin-1-ol; 9-(4-Fluorobenzylamino)-1,2,3,4-tetrahydroacridin-1-ol; 6-Chloro-9-(4-fluorobenzylamino)-1,2,3,4-tetrahydroacridin-1-ol; 9-(2-Chlorobenzylamino)-1,2,3,4-tetrahydroacridin-1-ol; 9-(3-Chlorobenzylamino)-1,2,3,4-tetrahydroacridin-1-ol; 9-(4-Chlorobenzylamino)-1,2,3,4-tetrahydroacridin-1-ol; 1,2,3,4-Tetrahydro-9-(2-trifluoromethylbenzyl)aminoacridin-1-ol; 6-Fluoro-1,2,3,4-tetrahydro-9-(2-trifluoromethylbenzylamino)acridin-1-ol; 1,2,3,4-Tetrahydro-9-(3-trifluoromethylbenzylamino)acridin-1-ol; 1,2,3,4-Tetrahydro-9-(4-trifluoromethylbenzylamino)acridin-1-ol; 9-[(2,3,4,5,6-Pentafluorobenzyl)amino]-1,2,3,4-tetrahydroacridin-1-ol; 9-Phenethylamino-1,2,3,4-tetrahydroacridin-1-ol; 9-(4,4-Diphenylbutyl)amino-1,2,3,4-tetrahydroacridin-1-ol; 9-[4,4-Bis(3-fluorophenyl)butylamino]-1,2,3,4-tetrahydroacridin-1-ol; 9-[4,4-Bis(4-fluorophenyl)butylamino]-1,2,3,4-tetrahydroacridin-1-ol; 9-(3-Phenoxypropylamino)-1,2,3,4-tetrahydroacridin-1-ol; 9-[[2-[Bis(4-fluorophenyl)methoxy]ethyl]amino]-1,2,3,4-tetrahydroacridin-1-ol; 9-[4-(Benzyloxy)benzylamino]-1,2,3,4-tetrahydroacridin-1-ol; 9-[(2-Thienyl)methylamino]-1,2,3,4-tetrahydroacridin-1-ol; 9-Amino-3,4-dihydroacridine; 9-Amino-1-methyl-1,2,3,4-tetrahydroacridin-1-ol; 9-Amino-3,4-dihydro-2-methyleneacridin-1(2H)-one; 9-Amino-1,2,3,4-tetrahydro-cyclopenta[b]quinolin-1-ol; 2-(3-Oxoclohexen-1-yl)aminobenzonitrile; and 4-Chloro-2-(3-oxocyclohexen-1-yl)aminobenzonitrile. The following examples are given for illustrative purposes. All temperatures are given in degrees Celsius. EXAMPLE 1 2-(3-oxocyclohexen-1-yl)aminobenzonitrile In 1.5 liters of tetrahydrofuran was added 98.32g of anthranilonitrile. The mixture was made acidic to litmus with concentrated HCl and with mechanical stirring was warmed to reflux. To the refluxing solution was added dropwise a solution containing 93.3g (1 eg) of 1,3-cyclohexadione in 7⊘⊘ml of tetrahydrofuran. After the addition was complete the reaction mixture was refluxed ⊘.5 hour more, then cooled and filtered to yield 161g (91%) of product as an HCl salt, melting point 2⊘6°C. A portion of the product was first washed with 1⊘% Na₂CO₃ (thus converting it to a free base) and then recrystallized from dichloromethane/hexanes to yield a powder, melting point 21⊘°C. EXAMPLE 2 4-Chloro-2-(3-oxocyclohexen-1-yl)aminobenzonitrile hydrochloride In 75ml of tetrahydrofuran was dissolved 5.⊘⊘g of 2-amino-4-chlorobenzonitrile. Into the mechanically stirred solution was bubbled HCl gas until a slurry was formed. The gas was disconnected and the slurry was brought to reflux. To the refluxing slurry was added dropwise over 1⊘ minutes a solution containing 3.67g (1.1 eq) of 1,3-cyclohexadione in 75ml of tetrahydrofuran. Reflux was continued for ⊘.5 hour during which the reaction went to completion. The slurry was cooled and filtered and the filter cake washed with tetrahydrofuran to yield 8.87g (96%) of a solid, melting point 229°C (with decomposition). EXAMPLE 3 9-Amino-3,4-dihydroacridin-1(2H)-one In 2 liters of tetrahydrofuran were combined 219.3g of 2-(3-oxocyclohexen-1-yl)aminobenzonitrile hydrochloride, 25⊘g (2 eq) of milled K₂CO₃, and 3g of CuCl catalyst. The mechanically stirred mixture was refluxed 5 hours and then filtered hot to remove the inorganic salts. The filtrate was evaporated to a residue and the residue was recrystallized twice from isopropanol to yield 77.4g (41%) of a powder, melting point 236-238°C. EXAMPLE 4 9-Benzylamino-3,4-dihydroacridin-1(2H)-one In a biphasic solution consisting of 15⊘ml of dichloromethane and 1⊘⊘ml of 50% aqueous NaOH were added 4.⊘⊘g of 9-amino-3,4-dihydroacridin-1(2H)-one, and ⊘.96g of tetrabutylammonium hydrogensulfate catalyst. The mixture was stirred mechanically for ⊘.5 hour and thereafter 2.47ml (1.1 eq) of benzyl bromide was added in one portion. After 4 hours of vigorous stirring, the reaction appeared complete based on thin layer chromatography analysis. The reaction mixture was poured into water/ice and the dichloromethane layer separated, dried over MgSO₄ and evaporated to a solid. The solid was recrystallized three times from dichloromethane/hexanes to yield 2.35g (41%) of product, melting point 162-163°C. EXAMPLE 5 3,4-Dihydro-9-(methylamino)acridin-1(2H)-one In 15⊘ml of dichloromethane and 1⊘⊘ml of 50% NaOH were added 5.⊘⊘g of 9-amino-3,4-dihydroacridin-1(2H)-one and ⊘.8⊘g (⊘.1 eq) of tetrabutylammonium hydrogensulfate. The biphasic mixture was mechanically stirred for ⊘.5 hour and thereafter 4.4ml (3 eq) of CH₃I was added. The reaction mixture was stirred overnight. Analysis of the reaction mixture indicated that the starting material was completely consumed. The reaction mixture was poured into cold water and the dichloromethane layer was separated, dried over MgSO₄ and filtered through alumina and the solvent was evaporated to afford a solid. The solid was recrystallized from dichloromethane/hexanes to yield 3.73g (7⊘%) of crystalline product after drying, melting point 116-117°C. EXAMPLE 6 9-Amino-1,2,3,4-tetrahydroacridin-1-ol In 1⊘⊘ml of dry tetrahydrofuran was added 5.⊘⊘g of 9-amino-3,4-dihydroacridin-1(2H)-one. The mechanically stirred suspension was cooled to -5°C and 21.4ml (1.⊘ eq) of 1.1 M LiAlH₄ solution in ether was added dropwise. After completion of the addition, the reaction mixture was stirred further for 2 hours, whereupon the reaction appeared complete based on thin layer chromatography analysis. The LiAlH₄ was neutralized with 2ml of saturated NH₄Cl and the salts were dissolved with 3⊘% potassium hydroxide. The insoluble product was filtered off and rinsed with water. The precipitate was then dissolved in 3N HCl and the residual insoluble salts filtered off. The acid solution was washed with EtOAc and made basic (pH 9) with 1⊘% NaOH. The precipitated product was filtered and washed with water. After drying at 8⊘°C under vacuum overnight, 4.15g (82%) of a powder was obtained, melting point 245°C. EXAMPLE 7 3,4-Dihydro-9-(n-propylamino)acridin-1(2H)-one In a mixture consisting of 15⊘ml of dichloromethane and 1⊘⊘ml of 5⊘% NaOH were combined 5.⊘⊘g of 9-amino-3,4-dihydroacridin-1(2H)-one and ⊘.8⊘g (.1⊘ eq) of tetrabutylammonium hydrogensulfate. The biphasic mixture was stirred for ⊘.5 hour and thereafter 6.9ml (3 eq) of n-propyl iodide was added and the stirring at room temperature was continued for 2 days during which three more portions of the above quantities of the alkylating agent were added at 12 hour intervals. The reaction was then complete based on thin layer chromatography analysis. The organics were separated and purified by passing through an alumina column (dichloromethane). The product was recrystallized from dichloromethane/Et₂O to yield 3.77g (63%) of a solid, melting point 145°C. EXAMPLE 8 9-Amino-3,4-dihydro-7-nitroacridin-1(2H)-one To 1⊘⊘ml of cold H₂SO₄ was added 5.⊘⊘g of 9-amino-3,4-dihydroacridin-1(2H)-one. The mechanically stirred solution was cooled to ⊘°C and 2.1ml (1 eq) of concentrated HNO₃ (7⊘ wt % solution) was added dropwise. Stirring was continued for 15 minutes after the addition, whereupon the reaction was complete. The reaction mixture was poured into excess crushed ice and made basic with a slight excess of 5⊘% NaOH solution. More ice was added during the neutralization to keep the solution cool. The resulting precipitate was filtered and chromatographed over silica gel (EtOAc). The fractions containing the product were evaporated to a solid which was triturated with pentane to yield 4.77g (79%) of a solid after drying, melting point 254°C (with decomposition). EXAMPLE 9 9-Methylamino-1,2,3,4-tetrahydroacridin-1-ol In 5⊘ml of dry tetrahydrofuran was dissolved 8.⊘⊘g of 3,4-dihydro-9-(methylamino)acridin-1(2H)-one. The mechanically stirred solution was cooled to -1⊘°C under N₂ and 32ml (1 eq) of 1.1 M LiAlH₄ solution in ether was added over 5 minutes. The stirring was continued for 45 minutes after the addition, during which the reaction went to completion. The excess LiAlH₄ was neutralized with 1ml of saturated NH₄Cl and the resulting salts dissolved in 3⊘% potassium hydroxide solution. The tetrahydrofuran solution was separated and evaporated to an oil which solidified upon trituration with 1:1 dichloromethane/hexanes. The solid was recrystallized from 1⊘:1 hexanes/tetrahydrofuran to yield 5.89g (73%) of a solid, melting point 16⊘-161°C. EXAMPLE 1 ⊘ 3,4-Dihydro-9-methylamino-7-nitroacridin-1(2H)-one In 1⊘⊘ml of concentrated H₂SO₄ at ⊘°C was added 4.83g of 3,4-dihydro-9-(methylamino)acridin-1(2H)-one. While maintaining the reaction at ⊘°C, 1.92ml (1 eq) of concentrated HNO₃ (7⊘ wt %)was added dropwise over 1⊘ minutes. Since the reaction appeared complete after the addition based on thin layer chromatography, the reaction mixture was poured into ice and neutralized with 5⊘% NaOH. At the basic point a precipitate formed. This was filtered and chromatographed on silica gel (EtOAc) and the product was recrystallized from dichloromethane/hexanes to yield 2.75g (47%) of a solid, melting point 2⊘8°C. EXAMPLE 11 9-(n-Propylamino)-1,2,3,4-tetrahydroacridin-1-ol In 5⊘ml of dry tetrahydrofuran was suspended 2.49g of 3,4-dihydro-9-(n-propylamino)acridin-1(2H)-one. The mechanically stirred suspension was cooled in ice and 4.5⊘ml (⊘.5 eq) of 1.1 M LiAlH₄ solution in ether was added dropwise, whereupon a solution formed. After the addition, the reaction appeared complete based on thin layer chromatography analysis. The excess hydride was neutralized with ⊘.5ml of saturated NH₄Cl solution and thereafter 3⊘% potassium hydroxide was added to dissolve the salts. The supernatent tetrahydrofuran solution was separted and evaporated to a solid. The solid was recrystallized from 1:4 dichloromethane/EtOAc to yield 1.88g (75%) of needles, melting point 164°C. EXAMPLE 12 9-Benzylamino-1,2,3,4-tetrahydroacridin-1-ol In 75ml of dry tetrahydrofuran was dissolved 3.81g of 9-benzylamino-3,4-dihydroacridin-1(2H)-one with mechanical stirring. The solution was cooled in ice under N₂ and 5.9ml (⊘.5 eq) of 1.1 M LiAlH₄ solution in ether was added dropwise. After ⊘.5 hour the reaction was complete based on thin layer chromatography analysis. The excess hydride was neutralized with ⊘.5ml of saturated NH₄Cl solution and the inorganic salts were extracted into 3⊘% potassium hydroxide. The tetrahydrofuran solution was decanted and evaporated to a solid which was recrystallized from 1:1⊘ dichloromethane/EtOAc to yield 2.89g (75%) of a solid, melting point 159°C. EXAMPLE 13 9-Amino-1-methyl-1,2,3,4-tetrahydroacridin-1-ol In 1⊘⊘ml of dry tetrahydrofuran was suspended 5.⊘⊘g of 9-amino-3,4-dihydroacridin-1(2H)-one at ice temperature and 78ml (4 eq) of 1.2M CH₃Li solution in ether was added thereto at such a rate as to avoid bubbling. The reaction mixture was stirred overnight as it warmed to ambient temperature. The next day 2⊘ ml more of the CH₃Li solution was added to drive the reaction to a completion. After ⊘.5 hour the reaction was quenched with excess water and 4.97g of the precipitate was collected and air dried. The product was recrystallized from MeOH/toluene. The yield was 2.⊘6g (38%) of granules, melting point 25⊘°C. EXAMPLE 14 9-Amino-3,4-dihydro-2-methyleneacridin-1(2H)-one In 25ml of trifluoroacetic acid cooled in ice was dissolved 5.⊘⊘g of 9-amino-3,4-dihydroacridin-1(2H)-one. To the solution was added dropwise 6.7⊘ml (2.⊘9 eq) of bisdimethylaminomethane over 5 minutes and thereafter the mixture was maintained at 9⊘-1⊘⊘°C for 5 hours during which the starting material was converted to a mixture of intermediate and exo-methylene products. The reaction mixture was poured into ice/NaOH to make it basic and the precipitate was extracted with several portions of 5:1 dichloromethane/MeOH. The combined extracts were evaporated to a residue. The residue was refluxed in toluene for 5 hours during which the intermediate was converted to the end product. The reaction mixture was evaporated to a residue which was purified by chromatography on silica gel (EtOAc) to yield about 2g of a solid. This was recrystallized from dichloromethane/EtOAc to yield 1.79g (34%) of product as a solid, melting point 192-193°C EXAMPLE 15 3,4-Dihydro-9-(2-fluorobenzylamino)acridin-1(2H)-one In a mixture consisting of 15⊘ml of dichloromethane and 1⊘⊘ml of 5⊘% NaOH were combined 5.⊘⊘g of 9-amino-3,4-dihydroacridin-1(2H)-one, 3ml (1 eq) of 2-fluorobenzylchloride and 1.2⊘g (⊘.15 eq) of tetrabutylammonium hydrogen sulfate. The biphasic mixture was mechanically stirred overnight and 3ml of 2-fluorobenzylchloride was again added. After 4 hours of further stirring, the reaction was complete based on thin layer chromatography. The reaction mixture was partitioned between water and dichloromethane and the dichloromethane layer was separated, dried over MgSO₄, filtered and evaporated to a solid. The solid was purified by chromatography on silica gel (EtOAc) and the resultant product was recrystallized from 1:4 EtOAc/toluene to yield 4.⊘9g (54%) of a solid, melting point 163.5-164°C. EXAMPLE 16 7,9-Diamino-3,4-dihydroacridin-1(2H)-one In 25⊘ml of glacial acetic acid was dissolved 4.43g of 9-amino-3,4-dihydro-7-nitroacridin-1(2H)-one and ⊘.44g of 1⊘% Pd/C was added. The mixture was put in a 5⊘⊘ml hydrogenation vessel (Parr) and was shaken under 3.8 bar (55 psig) (initial) H₂. The uptake of H₂ was 3 eq before the reaction as complete. The reaction was poured into ice and made basic with 1⊘% NaOH. The precipitate was filtered and dissolved in MeOH. The insoluble Pd/C catalyst was filtered off and the filtrate was diluted with toluene and concentrated until crystallization occurred. The yield was 2.84g (73%) of a solid, melting point 31⊘°C. EXAMPLE 17 3,4-Dihydro-9-(phenethylamino)acridin-1(2H)-one In a mixture consisting of 3⊘⊘ml of dichloromethane and 2⊘⊘ ml of 5⊘% NaOH were combined 1⊘.⊘⊘g of 9-amino-3,4-dihydroacridin-1(2H)-one, 28ml (6 eq) of 2-phenethyl bromide, and 3g (⊘.2 eq) of tetrabutylammonium hydrogensulfate catalyst. The mixture was mechanically stirred for 4 days, during which 28ml of 2-phenethyl bromide was added at intervals of 12 hours. After 4 days the layers were separated and the dichloromethane layer was evaporated to an oil, which was extracted into 3N HCl and washed with EtOAc. The HCl solution was then made basic with 1⊘% NaOH. The resulting precipitate was extracted into dichloromethane and the dichloromethane layer was evaporated to an oil containing mostly the starting material and the end product. The purification method was chromatography on silica gel with 2⊘% EtOAc/dichloromethane solvent. The product thus obtained was recrystallized from dichloromethane/hexanes to yield 2.52g (17%) of a solid, melting point 129-132°C. EXAMPLE 18 9-Amino-3,4-dihydroacridine hemihydrate In 5⊘ml of HOAc was dissolved 3.⊘⊘g of 9-amino-1,2,3,4-tetrahydroacridin-1-ol. To this mechanically stirred solution at room temperature was added ⊘.75ml (1 eq) of H₂SO₄. The reaction mixture was warmed on a steam bath causing a precipitate to form. After ⊘.5 hour of heating, the reaction was complete based on thin layer chromatography. The reaction mixture was poured into excess ice/1⊘% NaOH and the precipitate was collected. The precipitate was dissolved in dichloromethane, dried over MgSO₄, filtered, and evaporated to a solid which was purified by silica gel chromatography to yield a solid. Two recrystallizations from dichloromethane/hexanes yielded 1.4⊘g (52%) of a powder, melting point 178-179°C. EXAMPLE 19 N-[9-amino-3,4-dihydro-1(2H)-oxoacridin-7-yl]acetamide In 5⊘ml of glacial acetic acid was dissolved 3.⊘⊘g of 7,9-diamino-3,4-dihydroacridin-1(2H)-one. The mechanically stirred solution was cooled to 1⊘°C and 1.37ml (1.1 eq) of acetic anhydride was added. The solution was then heated on the steam bath for ⊘.5 hour during which the reaction went to completion. The reaction mixture was poured into ice and made basic with 1⊘% NaOH. The resulting emulsion was centrifuged and the supernatant decanted off. The solid was washed with water and recrystallized from 1:1⊘ MeOH/toluene to yield 2.25 (63%) of a solid, melting point over 26⊘°C. EXAMPLE 2 ⊘ 9-Amino-7-chloro-3,4-dihydroacridin-1(2H)-one In 5 liters of toluene were combined 2⊘⊘ml of dimethylformamide, 18⊘.71g of 5-chloro-2-(3-oxocyclohexen-1-yl)-aminobenzonitrile hydrochloride prepared in the same manner as the compounds of EXAMPLES 1 and 2, 176g (2 eq) of milled K₂CO₃ and 3g of cuprous chloride (CuCl). After 6 hours of reflux 3g more of CuCl was added. After 12 hours of reflux 3g more of CuCl was added. After overnight reflux the reaction mixture was evaporated and the residue extracted with dichloromethane via a Soxhlet extraction apparatus for 12 hours. The dichloromethane solution was evaporated to a solid. The solid was suspended in water and H₂SO₄ was added. The resultant salt which precipitated out was filtered and made basic with 1⊘% NaOH. The solid was filtered and recrystallized twice from isopropanol/toluene to yield 6.84g (4%) of a solid, melting point over 26⊘°C. EXAMPLE 21 3,4-Dihydro-9-(4,4-diphenylbutylamino)acridin-1(2H)-one In a mixture consisting of 48⊘ml of dichloromethane and 32⊘ml of 5⊘% NaOH were combined 8.⊘⊘g of 9-amino-3,4-dihydroacridin-1(2H)-one, 68g (6 eq) of 1-mesyloxy-4,4-diphenylbutane and 2.56g (⊘.2⊘ eq) of tetrabutylammonium hydrogensulfate used as a phase transfer catalyst. The biphasic mixture was jacket cooled to 3°C and was then mechanically stirred for 3 days. As no further reaction occurred, the reaction mixture was diluted with water and the organic phase was separated. Analysis by thin layer chromatography indicated a 1:1 mixture of the end product and the starting material. The dichloromethane layer was evaporated to a gum. The gum was diluted with dichloromethane and mixed with 1:1 alumina/sand to immobilize it as a solid for Soxhlet extraction. The dichloromethane was evaporated and the solid was put into a Soxhlet extraction thimble and extracted with hexane for 4 hours. Since no further extraction occurred after 4 hours, the hexane solution was evaporated to an oil. The oil was chromatographed over silica gel (EtOAc) and the resultant solid rechromatographed through alumina (Et₂O) to yield a solid. The solid was recrystallized from Et₂O/hexanes to yield 1.22g (8%) of product, melting point 86-88°C. EXAMPLE 22 9-(2-Fluorobenzylamino)-1,2,3,4-tetrahydroacridin-1-ol maleate In 25⊘ml of dry tetrahydrofuran was dissolved 4.89g of 3,4-dihydro-9-(2-flurobenzylamino)acridin-1(2H)-one. The mechanically stirred solution was cooled to ⊘°C under N₂ and 14ml (1 eq) of 1.1 M LiAlH₄ in Et₂O was added over ⊘.5 hour. After the addition the reaction was complete based on thin layer chromatography and hence it was quenched by adding 2ml of saturated NH₄Cl solution. The inorganics were filtered off and the tetrahydrofuran solution was evaporated to yield a product. The product was recrystallized from dichloromethane hexanes to yield 3.85g (78%) of a solid, melting point 14⊘-142°C. To further purify the product 3.39g of the product was converted to the maleate salt by combining it with 1.1 eq of maleic acid dissolved in isopropanol. The resulting precipitate was recrystallized from 1:4 MeOH/EtOAc to yield 3.75g of a solid, melting point 151-152°C. EXAMPLE 23 9-Phenethylamino-1,2,3,4-tetrahydroacridin-1-ol maleate In 75ml of dry tetrahydrofuran was dissolved 2.45g of 9-phenethylamino-3,4-dihydroacridin-1(2H)-one. The solution was cooled in ice and 7.⊘ml (1 eq) of 1.1 M LiAlH₄ in Et₂O was added dropwise. After ⊘.5 hour the reaction was complete. It was neutralized with ⊘.5ml saturated NH₄Cl solution and the resulting inorganic salts were filtered off. The filtrate was evaporated to a solid and the maleate salt was formed by adding a solution of 1.1 eq maleic acid in isopropanol to a suspension of the product in isopropanol. A solution formed initially but the salt precipitated out over ⊘.5 hour at ambient temperatures. The salt was filtered off and recrystallized from 5:1 EtOAc/MeOH and dried at 8⊘°C in vacuo to yield 1.14g (32%) of a solid, melting point 169°C. EXAMPLE 24 9-Amino-7-chloro-1,2,3,4-tetrahydroacridin-1-ol maleate In 5⊘ml of dry tetrahydrofuran was suspended 4.⊘⊘g of 9-amino-7-chloro-3,4-dihydroacridin-1(2H)-one. The mechanically stirred mixture was cooled in ice and 14.73ml (1 eq) of 1.1 M LiAlH₄ in ether was added dropwise. After ⊘.5 hour the reaction was complete. It was quenched with saturated NH₄Cl solution and the salts were extracted into 3⊘% potassium hydroxide. The biphasic mixture was diluted with hexanes and the product was collected by filtration, then washed with water and dried in vacuum to yield 3.⊘⊘g (75%) of a solid, melting point 164°C (with decomposition). The maleate salt was prepared by adding 1.1 eq of maleic acid in isopropanol to a suspension of 2.94g of the product in isopropanol. Initially a solution formed but within a few minutes the salt precipitated out. It was filtered and rinsed with Et₂O to yield 3.9⊘g (91%) of a solid. This was recrystallized from 1:1 MeOH/EtOAc to yield 2.79g (65%) of a solid, melting point 2⊘⊘°C (with decomposition). EXAMPLE 25 9-Amino-6-chloro-3,4-dihydroacridin-1(2H)-one In 2⊘⊘ml of tetrahydrofuran were combined 5.⊘⊘g of 4-chloro-2-(3-oxocyclohexen-1-yl)aminobenzonitrile hydrochloride, 4.88g (2 eq) milled anhydrous K₂CO₃, and ⊘.36g (⊘.1 eq) of CuBr (CH₃)₂S used as a catalyst. The mechanically stirred mixture was refluxed overnight. It was then evaporated to a residue and extracted with several portions of MeOH. The MeOH extract was evaporated and the residue was chromatographed on silica gel and then the purified product was recrystallized from EtOAc to yield 2.⊘7g (47%) of a solid, melting point 285-287°C. EXAMPLE 26 9-Amino-6-chloro-1,2,3,4-tetrahydroacridin-1-ol maleate In 6⊘ml of dry tetrahydrofuran was suspended 2.79g of 9-amino-6-chloro-3,4-dihydroacridin-1(2H)-one. The mechanically stirred suspension was cooled to ⊘°C and 1⊘.3ml (1 eq) 1.l M LiAlH₄ in ether was added slowly over 5 minutes. The mixture became a solution and after ⊘.5 hour the reaction was complete based on thin layer chromatography analysis. The reaction was quenched with 2⊘⊘ml of 3⊘% potassium hydroxide solution added slowly. The two layers were separated and the tetrahydrofuran layer was evaporated to a solid. The solid was suspended in water and a minimal amount of 3N HCl was added to dissolve it. The resultant aqueous solution was washed twice with EtOAc and made slightly basic with 1⊘% NaOH. The resultant precipitate was filtered and air dried to yield 2.76g (98%) of a solid, melting point 235-236°C. The solid was suspended in 25ml of isopropanol and a solution of 1.35g maleic acid in isopropanol was added thereto. A solution was formed first, but after stirring ⊘.5 hour the salt precipitated. The mixture was then further cooled in ice and filtered to yield 3.7⊘g of a solid. This was recrystallized from 1:1 EtOAc/MeOH to yield, after drying at 8⊘°C under vacuum, 2.41g (58%) of a solid, melting point 19⊘-191°C (with decomposition). EXAMPLE 27 9-Amino-3,4-dihydro-6-methylacridine-1(2H)-one, maleate To a suspension of N-(3-oxo-cyclohexen-1-yl)-2-amino-4-methylbenzonitrile (13.4 g) in 3⊘⊘ ml of tetrahydrofuran was added milled potassium carbonate (9.⊘ g) and cuprous chloride (6⊘⊘ mg). This was stirred at reflux for 5 hours. To the reaction mixture was then added 1⊘⊘ ml of warm ethanol and the inorganics were filtered off. The filtrate was then concentrated to give 8.7 g of a solid, mp 292-237°C decomp. A 2.3 g portion of this material was suspended in 1⊘⊘ ml of isopropanol and a slight excess of solid maleic acid was added. This was stirred for 5 hours, filtered and dried to give 3.⊘ g of an analytically pure powder, mp 197-198°C decomp. EXAMPLE 28 9-Amino-3,4-dihydro-6-methoxyacridin-1(2H)-one 2-Amino-4-methoxybenzonitrile (7.51 g) was suspended in 75 ml of benzene containing 6.⊘ g of cyclohexane-1,3-dione and 1.1 g of p -toluenesulfonic acid monohydrate. The reaction mixture was brought to reflux, at which time a homogeneous solution was obtained. After 15 minutes a thick precipitate developed, which was stirred in the refluxing solvent for an additional 15 minutes. At the end of this time thin layer chromatography (TLC, hereafter) showed that the starting material had been consumed, so the precipitate was filtered off, taken up in 2-butanone, and washed with sodium bicarbonate solution. The organic phase was dried and evaporated to a solid, which was triturated with ether to give 1⊘.61 g of the enamine, mp 194-196°C. This material was suspended in 25⊘ ml of tetrahydrofuran to which was then added 11.9 g of milled potassium carbonate and ⊘.85 g of CuCl. The reaction mixture was then refluxed for a total of 48 hours, with additional portions of CuCl (⊘.5⊘ g at a time) added at 6 hour and at 3⊘ hour. At the end of this time methanol (1⊘⊘ ml) was added to the reaction mixture and reflux was continued for 15 minutes. It was then filtered through diatomaceous earth, evaporated, and purified by flash chromatography (1⊘% methanol-dichloromethane). Obtained in this manner was 5.1 g of product that was suitable to be carried on to the next step. A 1.5 g portion was recrystallized from methanol to give 1.12 g of analytically pure material, mp 244-246°C. EXAMPLE 29 9-Amino-3,4-dihydro-6-fluoroacridin-1(2H)-one To a suspension of N-(3-oxo-cyclohexen-1-yl)-2-amino-4-fluorobenzonitrile (29.8 g) in 5⊘⊘ ml of tetrahydrofuran was added milled potassium carbonate (21.5 g) and cuprous chloride (1.3 g). This was heated at reflux for 1.5 hours. The reaction mixture was then diluted with 15⊘ ml of dichloromethane/methanol (1:1) and this was filtered. The warm solution was added directly to a column of magnesium silicate and eluted (ethanol/dichloromethane) to give 27.5 g of a powder, mp 269-273°C decomp. A portion of this was recrystallized from tetrahydrofuran to give analytically pure crystals, mp 266-269°C. EXAMPLE 3 ⊘ 9-Amino-3,4-dihydro-6-trifluoromethylacridin-1-(2H)-one, maleate To a solution of N-(3-oxo-cyclohexen-1-yl)-2-amino-4-trifluoromethylbenzonitrile (27.2 g) in 65⊘ ml of tetrahydrofuran were added potassium carbonate (26.8 g) and CuCl (1.9 g). This was heated at reflux for two hours. To this was added 15⊘ ml of ethanol, this was heated to reflux and the suspension was filtered warm. The filtrate was concentrated to a solid. A 3.7 g portion of the free base was recrystallized from methanol to give 2.⊘ g of a solid, mp 269-272°C. This was taken up in 1⊘⊘ ml of warm isopropanol and 25 ml of dichloromethane and the solution was acidified with a solution of maleic acid in isopropanol. The solid which crystallized out was collected to give 2.5 g of a solid, mp 2⊘9-21⊘°C decomp. EXAMPLE 31 9-Amino-2,3-dihydro-cyclopental[b]quinolin-1-one, maleate A suspension of N-(3-oxo-cyclopenten-1-yl)-2-aminobenzonitrile (9.7 g), potassium carbonate (7.4 g) and cuprous chloride (495 mg) in 2⊘⊘ ml of diglyme (diethylene glycol dimethyl ether) was heated at 125°C for 2.5 hours. The suspension was then solubilized with 14⊘ ml of methanol/dichloromethane and passed through a column of magnesium silicate (ethanol/dichloromethane). The fractions were concentrated to diglyme only and thereafter water was added. The resulting solid was filtered and dried to give 3.7 g of powder, mp 286-19⊘°C. This was recrystallized from isopropanol to give 2.⊘ g of powder. This was suspended in 1⊘⊘ ml of isopropanol to which was added maleic acid (1.1 equivalent). The resultant solid was filtered and recrystallized from methanol/diethyl ether to give 2.4 g of powder, mp 191-193°C d. EXAMPLE 32 3,4-Dihydro-9-[2(dimethylamino)ethyl]aminoacridin-1(2H)-one To a suspension of 9-amino-3,4-dihydroacridin-1(2H)-one (1⊘.⊘ g) in 1⊘⊘ ml of dimethylformamide was added a 5⊘% suspension of sodium hydride in oil (2.9 9). To this was added 2-dimethylaminoethyl chloride (6.5 g). The mixture was heated to 6⊘°C pot temperature for 2.5 hours, an additional 2.7 g of the chloride was added and this was heated for an additional 1 hour. The reaction was then quenched with 2⊘⊘ ml of water and the aqueous phase was extracted with ethyl acetate (3X). The combined organics were then dried over anhydrous magnesium sulfate and preadsorbed on silica. The desired amine was purified via flash chromatography (ethyl acetate, then progressing to 1⊘% methanol/ethyl acetate) to give 2.65 g of a solid, mp 126-135°C. This was recrystallized from n-butyl acetate to give 1.3 g of an analytically pure solid, mp 14⊘-143°C. EXAMPLE 33 9-Benzylamino-3,4-dihydro-6-methylacridin-1(2H)-one, maleate To a suspension of 9-amino-3,4-dihydro-6-methylacridin-1(2H)-one (8.⊘ g) in 75 ml of dimethylsulfoxide was added pulverized potassium hydroxide (6.⊘ g). This was stirred to solution and benzyl bromide (7.3 g) was added. This was stirred for 1.5 hours at which time 2⊘⊘ ml of water was added to the reaction flask. The precipitate was filtered, rinsed with water, taken up with dichloromethane and dried over anhydrous magnesium sulfate. The desired amine was purified via flash chromatography (8% isopropanol/toluene to yield 3.3 g of a solid, mp 141-149°C. A 1.5 g portion of this material was suspended in 8⊘ ml of isopropanol and 621 mg of maleic acid was added. This was stirred for 3 hours, filtered and dried to give 1.65 g of a powder, mp 151-153°C. EXAMPLE 34 9-Benzylamino-3,4-dihydro-6-fluoroacridin-1(2H)-one, maleate To a suspension of 9.⊘ g of 9-amino-3,4-dihydro-6-fluoroacridin-1(2H)-one in 8⊘ ml of dimethylsulfoxide was added pulverized potassium hydroxide (6.1 g). This was stirred to solution and benzyl bromide (8.4 g) was added, After stirring for 1.5 hours, 2⊘⊘ ml of water was added to the reaction flask. The precipitate was filtered, rinsed with water, dissolved in dichloromethane and dried over anhydrous magnesium sulfate. The resulting solid was triturated with ethyl ether to give 8.8 g of a solid, mp 14⊘-15⊘°C. A 3.25 g portion was suspended in isopropanol (8⊘ ml) and 1.3 g of maleic acid was added. The suspension was stirred for 3 hours and filtered to give 3.7 g of a solid, mp 135-186°C. This was recrystallized from 15⊘ ml of methanol/isopropanol (2:1) to give 2.⊘5 g of analytically pure powder, mp 19⊘-191°C. EXAMPLE 35 9-Benzylamino-6-chloro-3,4-dihydroacridin-1(2H)-one In a biphasic solution comprised of 15⊘ ml of toluene and 1⊘⊘ ml of 3⊘% potassium hydroxide were added 3.⊘⊘ g of 9-amino-6-chloro-3,4-dihydroacridin-1(2H)-one and ⊘.62 g of tetrabutylammonium hydrogen sulfate. The reaction was mechanically stirred and brought to reflux (b.p. 9⊘°C) with a steam bath. To the refluxing mixture was added a solution of 3.⊘4 ml of benzyl bromide in 2⊘ ml of toluene over ⊘.5 hour. Within 1 hour the reaction was complete by TLC. The toluene layer was separated and the aqueous layer was extracted with ethyl acetate. The organics were combined, dried over anhydrous magnesium sulfate, filtered and evaporated to a solid. The solid was recrystallized from dichloromethane/hexane to yield 1.63 g of a solid, mp 141-143°C. EXAMPLE 36 9-Benzylamino-3,4-dihydro-6-trifluoromethylacridin-1(2H)-one To a suspension of 7.⊘ g of 9-amino-3,4-dihydro-6-trifluoromethylacridin-1(2H)-one in 75 ml of dimethylsulfoxide was added 6 g of pulverized potassium hydroxide. This was stirred for 1⊘ minutes at ambient temperature. At this time was added benzyl bromide (5.2 g). This was stirred for 2 hours at room temperature. To the reaction was then added 2⊘⊘ ml of water. The aqueous phase was extracted with ethyl acetate (3X) and the combined organics were washed. with water and dried (saturated sodium chloride solution, anhydrous magnesium sulfate). The desired amine was purified via flash chromatography (3% i-PrOH/C₆H₅CH₃) to yield 5.4 g of a solid, mp 128-134°C. A portion of this was recrystallized from isopropyl ether to give an analytically pure solid, mp 136-138.5°c. EXAMPLE 37 3,4-Dihydro-9-(2-methylbenzylamino)acridin-1-(2H)-one 9-amino-3,4-dihydroacridin-1(2H)-one (7.63 g) was suspended in 75 ml of dimethylsulfoxide and 5 g of pulverized 85% potassium hydroxide was added. After 45 minutes a homogeneous solution was obtained to which was added 7.⊘ g of 2-methylbenzyl bromide. The reaction mixture was stirred for 3⊘ minutes and then additional 2.⊘ g of the benzyl bromide was added. After 6⊘ more minutes 3⊘⊘ ml of water and 3⊘ ml of ether were added to the reaction. The precipitated product was filtered off and washed with additional ether, then flushed over a short magnesium silicate column with ethyl acetate. After evaporating the solvent, the product was again washed with cold ether to give 7.21 g of product. EXAMPLE 38 3,4-Dihydro-9-(3-methylbenzylamino)acridin-1(2H)-one 9-amino-3,4-dihydroacridin-1(2H)-one (7.⊘ g) was suspended in 75 ml of dimethylsulfoxide and 5.⊘ g of pulverized 85% potassium hydroxide was added. After stirring for 3⊘ minutes 7.⊘ g of 3-methylbenzyl bromide was added dropwise. After an additional 3⊘ minutes, another 2.⊘ g of the benzyl bromide was added. A total of 9⊘ minutes after the addition of the potassium hydroxide, 3⊘⊘ ml of water was added to the reaction mixture and the product was extracted into ethyl acetate. Evaporation of the solvent gave a product that was washed with ether and then flushed over a short magnesium silicate column with ethyl acetate. Evaporation of the solvent gave 6.31 g of product. Analytically pure material was obtained by recrystallization from cyclohexane, mp 134-136°C. EXAMPLE 39 3,4-Dihydro-9-(4-methylbenzylamino)acridin-1(2H)-one 9-amino-3,4-dihydroacridin-1(2H)-one (8.⊘ g) was suspended in 75 ml of dry dimethylsulfoxide and 6 g of pulverized 85% potassium hydroxide was added. After 1 hour a homogeneous solution was obtained. To this was added 7.4 g of 4-methylbenzyl bromide. After stirring for 6⊘ minutes 2⊘⊘ ml of water was added to the reaction mixture and then the granular precipitate was filtered off. It was taken up in dichloromethane, dried and purified by flash chromatography (5% i-PrOH/toluene) to yield 8.4 g of product. Analytically pure material was obtained by recrystallization from benzene-pentane, mp 143-144°C. EXAMPLE 4⊘ 3,4-Dihydro-9-(2-methoxybenzylamino)acridin-1(2H)-one hemihydrate Eight grams of 9-amino-3,4-dihydroacridin-1(2H)-one was suspended in 75 ml of dimethylsulfoxide and 6 g of pulverized 85% potassium hydroxide was added. After 3⊘ minutes 9.⊘ g of 2-methoxybenzyl bromide was added dropwise and after another 3⊘ minutes an additional 1.5 g of the benzyl bromide was added. A total of 9⊘ minutes after the addition of the potassium hydroxide, 3⊘⊘ ml of water was added to the reaction mixture, and the precipitated product was filtered off, dissolved in dichloromethane and dried. The solvent was evaporated and the residue purified by flash chromatography (1⊘% i-PrOH/toluene) to give 1⊘.9 g of product. Analytically pure material was obtained by recrystallization from benzene-pentane, mp 111-112°C. EXAMPLE 41 3,4-Dihydro-9(3-methoxybenzylamino)acridin-1(2H)-one Eight grams of 9-amino-3,4-dihydroacridin-1(2H)-one was suspended in 75 ml of dimethylsulfoxide and powdered 85% potassium hydroxide (6.⊘ g) was added. After 3⊘ minutes 3-methoxybenzyl bromide (9.⊘ g) was added dropwise. After an additional 6⊘ minutes 2⊘⊘ ml of water was added to the reaction mixture and the resultant, slightly gummy precipitate was filtered off. It was taken up in dichloromethane, dried, concentrated and purified by flash chromatography (5% isopropanol/toluene) to give 9.⊘ g of product. Analytically pure material was obtained by recrystallization from dichloromethane/ether, mp 85-87°C. EXAMPLE 42 3,4-Dihydro-9-(4-methoxybenzylamino)acridin-1(2H)-one Eight grams of 9-amino-3,4-dihydroacridin-1(2H)-one was suspended in 75 ml of dry dimethylsulfoxide (DMSO hereafter) and 3 g of pulverized 85% potassium hydroxide was added. After 1 hour a homogeneous solution was obtained. To this solution was added 8.⊘ g of 4-methoxybenzyl bromide. After stirring for 9⊘ minutes 3⊘⊘ ml of water was added to the reaction mixture and the product was extracted into ethyl acetate (EtOAc hereafter). The organic phase was dried, concentrated, and purified by flash chromatogrpahy (5% methanol-dichloromethane) to give 6.1 g of product as a powder. Analytically pure material was obtained by recrystallization from benzene-pentane, mp 115-117°C. EXAMPLE 43 3,4-Dihydro-9-(3-fluorobenzylamino)acridin-1(2H)-one In 3⊘⊘ ml of toluene and 2⊘⊘ ml of 3⊘% potassium hydroxide were combined 8.⊘⊘ g of 9-amino-3,4-dihydroacridin-1(2H)-one and 1.92 g of tetrabutylammonium hydrogen sulfate catalyst. The mechanically stirred mixture was heated to reflux and a solution of 9.25 ml of 3-fluorobenzyl bromide in 4⊘ ml of toluene was added over ⊘.5 hour. Then the reaction was further refluxed for 2 hours. The reaction mixture was then poured into 5⊘⊘ ml of ice and the layers were separated. The aqueous layer was extracted with ethyl acetate. The organics were combined and washed with saturated NaCl solution, dried over magnesium sulfate, filtered and evaporated to a solid. The solid was purified by preparative HPLC (ethyl acetate). The product-containing fractions were combined and concentrated to a solid. The solid was recrystallized from 1:1 dichloromethane/pentane to yield 7.15 g of solid, mp 156-157°C. EXAMPLE 44 3,4-Dihydro-9-(4-fluorobenzylamino)acridin-1(2H)-one In 3⊘⊘ ml of toluene and 2⊘⊘ ml of 3⊘% potassium hydroxide were added 8.⊘⊘ g of 9-amino-3,4-dihydroacridin-1(2H)-one and 1.92 g of tetrabutylammonium hydrogen sulfate catalyst. The mechanically stirred biphasic solution was heated to reflux and 9.4 ml of 4-fluorobenzyl bromide in 5⊘ ml of toluene was added dropwise. Reflux was continued for a total of 2 hours. The reaction was poured onto ice and the toluene layer was separated. The aqueous phase was extracted with ethyl acetate. The organics were combined, washed with saturated NaCl solution, dried over anhydrous magnesium sulfate, filtered and evaporated to a solid. The solid was recrystallized from 1:1 ethyl acetate/hexane to yield 5.89 g of product, mp 158-159°C. EXAMPLE 45 6-Chloro-3,4-dihydro-9-(4-fluorobenzylamino)acridin-1(2H)-one In 3⊘⊘ ml of toluene and 2⊘⊘ ml of 3⊘% potassium hydroxide were added 9.⊘⊘ g of 9-amino-6-chloro-3,4-dihydroacridin-1(2H)-one and 3.1⊘ g of tetrabutylammonium hydrogen sulfate catalyst. The mechanically stirred solution was warmed to reflux (9⊘°C) and 9.54 ml of 4-fluorobenzyl bromide in 5⊘ ml of toluene was added dropwise over ⊘.5 hours. After refluxing 3 hours the reaction was complete by TLC. It was poured into 5⊘⊘ ml of ice. The aqueous phase was separated and extracted with dichloromethane (DCM hereafter). The organic layers were combined and washed with saturated NaCl solution, dried over anhydrous magnesium sulfate, filtered and evaporated to an oil. The oil was purified by preparative HPLC (1:1 et acetate/hexane) and the product-containing fractions were combined and evaporated to a solid. The solid was recrystallized from 1:1 DCM/pentane to yield 6.1⊘ g of solid, mp 156-157.5°C. EXAMPLE 46 9-(2-Chlorobenzylamino)-3,4-dihydroacridin-1(2H)-one To a suspension of 9-amino-3,4-dihydroacridin-1(2H)-one (8.⊘ g) in 75 ml of dimethyl sulfoxide was added pulverized potassium hydroxide (6.2 g). This was stirred for ⊘.5 hour at ambient temperature. To this solution was added 2-chlorobenzyl bromide (9.4 g). After 1 hour, an additional 1 ml of the bromide was added. This was stirred for an additional hour. At this time, 2⊘⊘ ml of water was added, and the precipitate was filtered and washed with water. The solid was taken up in dichloromethane and dried over anhydrous magnesium sulfate. The compound was purified via flash chromatography to yield 6.75 g of solid, mp 15⊘-161°C. A portion of this was recrystallized from methanol to give analytically pure needles, mp 162-165°C. EXAMPLE 47 9-(3-Chlorobenzylamino)-3,4-dihydroacridin-1(2H)-one To a suspension of 9-amino-3,4-dihydroacridin-1(2H)-one (8.⊘ g) in 75 ml of dimethylsulfoxide was added 6 g of pulverized potassium hydroxide. This was stirred at ambient temperature for 45 minutes. To this was then added 3-chlorobenzyl bromide (8.22 g). After 1.5 hours, another 2.5 ml of the benzyl bromide was added. This was stirred for an additional 45 minutes. At this time 21⊘ ml of water was added to the reaction vessel. This was stirred to a granular precipitate which was filtered and rinsed with water and diethyl ether. The solid was filtered and stirred in ether and again filtered and dried to yield 6.⊘ g of a solid, mp 137.5-14⊘°C. A portion of this was recrystallized from toluene/hexane (1:1) to give an analytically pure solid, mp 139-141°C. EXAMPLE 48 9-(4-Chlorobenzylamino)-3,4-dihydroacridin-1(2H)-one To a suspension of 9-amino-3,4-dihydroacridin-1(2H)-one (8.⊘ g) in 75 ml of dimethyl sulfoxide was added pulverized potassium hydroxide (6.1 g). This was stirred at room temperature for ⊘.5 hour. To this solution was added 4-chlorobenzyl chloride (7.63 g) dissolved in 1⊘ ml of dimethyl sulfoxide. This solution was stirred for 3.5 hours at room temperature. To the reaction mixture was then added 2⊘⊘ ml of water. This was stirred for ⊘.5 hour after which the precipitate was collected, washed with water, taken up in dichloromethane and dried over anhydrous magnesium sulfate. This was concentrated to a solid which was triturated with ethyl ether to give 9.3 g of a solid, mp 162-164.5°C. EXAMPLE 49 3,4-Dihydro-9-[(2,3,4,5,6-pentafluorobenzyl)amino]acridin-1(2H)-one To a suspension of 9-amino-3,4-dihydroacridin-1(2H)-one (7.45 g) in 7⊘ ml of dimethylsulfoxide was added pulverized potassium hydroxide (6 g). To the resulting solution was added pentafluorobenzyl bromide (1⊘.5 g). This was stirred at ambient temperature for 2 hours. The reaction mixture was then added to 2⊘⊘ ml of water and extracted with ethyl acetate (3X). The combined organics were washed with water and dried over anhydrous magnesium sulfate. This was added directly to a column of magnesium silicate and eluted with ethyl acetate, whereupon a dark oil was obtained. The desired amine was purified via flash chromatography (ethyl acetate) to obtain 5.8 g of a solid, mp 119-124°C. A 2.⊘ g portion of this solid was recrystallized from ethyl acetate/hexane (1:4) to obtain 1.3 g of an analytically pure powder, mp 122-124°C. EXAMPLE 5⊘ 3,4-Dihydro-9-(2-trifluoromethylbenzylamino)acridin-1(2H)-one In 3⊘⊘ ml of toluene and 2⊘⊘ ml of 3⊘% potassium hydroxide were combined 8.⊘⊘ g of 9-amino-3,4-dihydroacridin-1(2H)-one and 3.2⊘ g of tetrabutylammonium hydrogen sulfate. The biphasic mixture was mechanically stirred and warmed to reflux (9⊘°C) and 3⊘.⊘ g of 2-trifluoromethylbenzyl bromide in 5⊘ ml of toluene was added dropwise over 1 hour. After the addition, heating was maintained for 2 hours during which the reaction went to completion. It was poured into 5⊘⊘ ml of ice and the layers were separated. The aqueous phase was extracted with DCM. The organic solutions were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and evaporated to an oil which was purified by preparative HPLC (ethyl acetate). The product-containing fractions were evaported to a solid which was recrystallized from 1:1 ethyl acetate/hexanes to yield 6.49 g of solid, mp 167°C. EXAMPLE 51 3,4-Dihydro-6-fluoro-9-(2-trifluoromethylbenzylamino)acridin-1(2H)-one To a suspension of 7.6 g of 9-amino-3,4-dihydro-6-fluoroacridin-1(2H)-one in 85 ml of dimethylsulfoxide was added pulverized potassium hydroxide (6.⊘ g). This was stirred to solution and 2-trifluoromethylbenzyl chloride (7.8 g) was added. This was stirred for a total of 2 hours during which time 2 aliquots of 1 ml of the benzyl chloride was added to the reaction. To the reaction vessel was then added 21⊘ ml of water and the granular precipitate was filtered, washed with water, dissolved in dichloromethane and dried over anhydrous magnesium sulfate. This was concentrated to a solid which was triturated with ether to give 1⊘.3 g of a solid, mp 146-151°C. A 4.⊘ g portion of this was recrystallized from n-butyl acetate (2⊘ ml) to yield 3.2 g of an analytically pure powder, mp 149-152°C. EXAMPLE 52 3,4-Dihydro-9-(3-trifluoromethylbenzylamino)acridin-1(2H)-one In 15⊘ ml of toluene and 7⊘⊘ ml of 3⊘% potassium hydroxide were combined 3.⊘⊘ g of 9-amino-3,4-dihydroacridin-1(2H)-one and ⊘.72 g of tetrabutylammoniun hydrogen sulfate. The reaction was mechanically stirred and heated with a steam bath. To it was added dropwise a soluton of 13.5 g 3-trifluoromethylbenzyl bromide in 3⊘ ml of toluene over 1 hour. After the addition, heating was continued 1 hour during which the reaction went to completion. The organic phase was separated, washed with ice-cold saturated NaCl solution, dried over anhydrous magnesium sulfate, filtered and evaporated to an oil. The oil was diluted with 1⊘ ml of ethyl acetate and purified by preparative HPLC (ethyl acetate). The product-containing fractions were evaporated and recrystallized from DCM/hexane to yield 2.2⊘ g of solid, mp 147-149°C. EXAMPLE 53 3,4-Dihydro-9-(4-trifluoromethylbenzylamino)acridin-1(2H)-one In 3⊘⊘ ml of toluene and 2⊘⊘ ml of 3⊘% potassium hydroxide were combined 8.⊘⊘ g of 9-amino-3,4-dihydroacridin-1(2H)-one and 3.2⊘ g of tetrabutylammonium hydrogen sulfate catalyst. The mechanically stirred mixture was warmed to reflux and 3⊘.⊘ g of 4-trifluoromethylbenzyl bromide in 5⊘ ml of toluene was added dropwise over 1 hour. After stirring at reflux for 4 hours the reaction was complete by TLC. It was poured into 5⊘ ml of ice and the aqueous layer was separated and extracted with DCM. The organics were combined, washed with saturated NaCl solution, dried over anhydrous magnesium sulfate and evaporated to an oil. The oil was purified by preparative HPLC (ethyl acetate) and the isolated product was recrystallized from dichloromethane/pentane (1:1) to yield 3.87 g of solid, mp 174-176°C. EXAMPLE 54 3,4-Dihydro-9-(4,4-diphenylbutylamino)-6-trifluoromethylacridin-1(2H)-one, maleate To a suspension of 9-amino-3,4-dihydro-6-trifluoromethylacridin-1(2H)-one in 125 ml of dimethylformamide was added potassium tertiarybutoxide (3.6 g). To the resulting solution was added 4,4-diphenylbutylmethane sulfonate (8.4 g). After 3 hours, an additional ⊘.8 g of the mesylate and 1 g of the butoxide were added. This was stirred for an additional hour and then quenched with 3⊘⊘ ml of water. The aqueous phase was extracted with ethyl acetate (2X) and the combined organics were washed with water and dried (saturated NaCl solution, magnesium sulfate). This was added directly to a column of magnesium silicate and eluted with ethyl acetate to obtain a dark oil. The desired amine was purified via preparative HPLC (5% ethyl acetate/dichloromethane) to obtain 2.15 g of a solid, mp 13⊘-133°C. This was dissolved in ethyl ether and acidified with a solution of maleic acid in isopropanol. The precipitate was collected and dried to obtain 2.4 g of a powder, mp 129-133°C. This was recrystallized from cyclohexane/acetone (3:1) to obtain 2.1⊘ g of solid, mp 139-142°C decomp. EXAMPLE 55 3,4-Dihydro-9-[4,4-bis(3-fluorophenyl)butylamino]acridin-1(2H)-one To a suspension of 8.⊘ g of 9-amino-3,4-dihydro-acridin-1(2H)-one in 125 ml of dimethylformamide was added potassium tert-butoxide (5.5 g). To this was added 4,4-bis(3-fluorophenyl)butyl methane sulfonate (15.15 g). This was stirred at 9⊘°C for six hours. The reaction mixture was then poured into 5⊘⊘ ml of water and extracted with ethyl acetate (3X). The organics were washed with water (2X) and dried (saturated NaCl solution, anhydrous magnesium sulfate). The amine was purified via flash chromagography (8% i-PrOH/toluene) and then passed through a column of magnesium silicate (ethyl acetate) to yield 11.3 g of a solid, mp 78-85°C. A portion of this was twice recrystallized from cyclohexane to obtain an analytically pure solid, mp 86-89°C. EXAMPLE 56 3,4-Dihydro-9-[4,4-bis(4-fluorophenyl)butylamino]acridin-1(2H)-one, maleate To a suspension of 8.⊘ g of 9-amino-3,4-dihydroacridin-1(2H)-one in 15⊘ ml of dimethylformamide were added potassium tert-butoxide (6.4 g) and 4,4-bis(4-fluorophenyl)-butyl chloride(14.⊘ g). This was heated at 85°C for 5 hours. The reaction mixture was then quenched into 4⊘⊘ ml of water and the aqueous phase was extracted with ethyl acetate (3X). The combined organics were washed with water and dried (saturated NaCl solution, anhydrous magnesium sulfate). The desired amino ketone was purified via flash chromatography (7% i-PrOH/toluene) to yield 6.7 g of a powder, mp 128-132°C. A 3.⊘ portion of this was dissolved in 85 ml of isopropanol and acidified with a solution of maleic acid in isopropanol. The solid which crystallized out was collected and dried to give 3.25 g of a powder, mp 162-165°C decomp. EXAMPLE 57 9-(3-Phenoxypropylamino)-3,4-dihydroacridin-1(2H)-one In 6⊘⊘ ml of toluene and 4⊘⊘ ml of 3⊘% potassium hydroxide were combined 1⊘.⊘⊘ g of 9-amino-3,4-dihydroacridin-1(2H)-one, 39 ml of 3-phenoxypropyl bromide and 3.2 g of tetrabutylammonium hydrogen sulfate catalyst. The biphasic mixture was refluxed (bp 9⊘°C) with mechanical stirring for 5 hours, during which the reaction went to completion. The organic phase was separated, washed with ice cold saturated NaCl solution, dried over anhydrous magnesium sulfate, filtered and evaporated to an oil. The oil was flash chromatographed (silica, ethyl acetate) and the product-containing fractions were combined and evaporated to an oil. Trituration with ether yielded the product as a solid which was recrystallized from dichloromethane/hexane to yield 4.45 g of product, mp 1⊘4-1⊘6°C. EXAMPLE 58 9-[2-[Bis(4-fluorophenyl)methoxy]ethylamino]-3,4-dihydroacridin-1(2H)-one, maleate To a cooled suspension of sodium hydride (1.15 g) in 2⊘ ml of dimethylformamide was added a solution of 8.5 g of 9-amino-3,4-dihydroacridin-1(2H)-one in 15⊘ ml of dimethylformamide. This was stirred for 1⊘ minutes at room temperature. At this time, 13.5 g of 2-[Bis(4-fluorophenyl)methoxy]ethyl chloride was added. This was heated at 7⊘°C for 12 hours. The reaction mixture was then poured to ice-water and extracted with ethyl acetate (3X). The combined organics were washed with water and dried (saturated NaCl solution, anhydrous mangesium sulfate). This was then passed through a short column of magnesium silicate (ethyl acetate) and concentrated to a semi-solid. The desired amine was purified via flash chromatogrpahy (7% isopropanol/toluene) to give 11.6 g of an oil. This was dissolved in ethyl ether and one-half of this solution was taken. The maleate salt was prepared from ether solution to give 4.45 g of a solid, mp 169-173°C d. This was recrystallized from isopropanol/methanol (3:1, 2⊘⊘ ml total volume) to give 2.6 g of an analytically pure powder, mp 176-178°C d. EXAMPLE 59 9-[4-(Benzyloxy)benzylamino]-3,4-dihydroacridin-1(2H)-one To a suspension of 17.7 g of 9-amino-3,4-dihydroacridin-1(2H)-one in 15⊘ ml of dimethylsulfoxide was added pulverized potassium hydroxide (11 g). To the resulting solution was added 4-benzyloxybenzyl chloride (25 g). This was stirred at ambient temperature for 2.5 hours. To the reaction vessel was then added 4⊘⊘ ml of water. This was stirred until a granular precipitate was formed which was filtered, rinsed with water, taken up in dichloromethane and dried over anhydrous magnesium sulfate. The resulting semi-solid was triturated (ethyl acetate) to a solid which was passed through a column of mangesium silicate (DCM, then ethyl acetate). This gave 23.8 g of a solid, mp 153-157°C. A portion of this was recrystallized from n-butyl acetate to give an analytically pure solid, mp 156-159°C. EXAMPLE 6⊘ 3,4-Dihydro-9-[(2-thienyl)methylamino]acridin-1(2H)-one, maleate To a suspension of 8.⊘ g of 9-amino-3,4-dihydroacridin-1(2H)-one in 75 ml of dimethylsulfoxide was added pulverized potassium hydroxide. To the resulting solution was added 2-chloromethylthiophene. This was stirred at ambient temperature for 3 hours. To the reaction mixture was then added 21⊘ ml of water. The resulting precipitate was collected, rinsed with water, dissolved in dichloromethane and dried over anhydrous magnesium sulfate. This was concentrated to a solid which was triturated with ether to give 8.5 g of a solid, mp 127-133°C. A 4.⊘ g portion was recrystallized from cyclohexane to give 2.8 g of a powder, mp 133°-136°C. This was dissolved in isopropanol/methanol (125 ml:25 ml) and acidified with a solution of maleic acid in isopropanol. The resulting crystals were collected and dried to obtain 3.⊘ g of analytically pure powder, mp 174-175°C decomp. EXAMPLE 61 9-Amino-6-methoxy-1,2,3,4-tetrahydroacridin-1-ol maleate 9-Amino-3,4-dihydro-6-methoxyacridin-1(2H)-one was suspended in 1⊘⊘ ml of tetrahydrofuran (THF hereafter) and then 17 ml of 1M LiAlH₄ in THF was added. Ten minutes after the addition, the reaction mixture was still a suspension but TLC showed that the starting material had been consumed. The reaction was quenched by the sequential addition of ⊘.6 ml of water, ⊘.6 ml of 15% sodium hydroxide and 1.8 ml of water. The inorganics were filtered off and washed well with hot THF, and the filtered liquid was combined and concentrated, and the residue triturated with ethyl acetate. The maleate salt was formed by suspending this product in about 5⊘ ml of hot i-ProH and adding a slight excess of maleic acid. This treatment gave a homogeneous solution to which was added ether until crystallization began. After crystallization was complete the maleate salt was filtered off and dried to obtain 4.6⊘ g of solid, mp 179-18⊘°C. EXAMPLE 62 9-Amino-6-fluoro-1,2,3,4-tetrahydroacridin-1-ol To a cooled suspension of 5.⊘ g of 9-amino-3,4-dihydro-6-fluoroacridin-1(2H)-one in 85 ml of tetrahydrofuran was added 22 ml of 1M solution of lithium aluminum hydride in tetrahydrofuran. This was stirred for 1 hour and then quenched with 8 ml of saturated ammonium chloride solution. The inorganics were filtered and rinsed with ethyl acetate, and the combined organics were dried over anhydrous magnesium sulfate. This was filtered and concentrated to obtain 5.⊘ g of a powder, mp 2⊘3-2⊘6°C d. This was recrystallized from tetrahydrofuran/hexane to obtain 3.95 g of an analytically pure powder, mp 2⊘7-2⊘9°C d. EXAMPLE 63 9-Amino-1,2,3,4-tetrahydro-6-trifluoromethylacridin-1-ol 9-Amino-3,4-dihydro-6-trifluoromethylacridin-1(2H)-one (2.4 g) was suspended in 6⊘ ml of tetrahydrofuran. To this cooled solution was added 9 ml of 1 molar solution of lithium aluminum hydride in THF. This was stirred for 3⊘ minutes. The reaction was quenched with 5 ml of saturated ammonium chloride solution. This was then diluted with ethyl acetate and the inorganics were filtered and rinsed with ethyl acetate. The combined organics were then dried over anhydrous magnesium sulfate and concentrated to obtain 2.4 g of a solid, mp 221-225°C decomp. This was combined with 1.4 g from a previous reaction and recrystallized from tetrahydrofuran/hexane (1:1) to obtain 2.1 g of an analytically pure powder, mp 224-226°C decomp. EXAMPLE 64 9-[2-(Dimethylamino)ethyl]amino-1,2,3,4-tetrahydroacridin-1-ol To a cooled solution of 4.4 g of 3,4-dihydro-9-[2-(dimethylamino)ethylamino]acridin-1(2H)-one in 8⊘ ml of tetrahydofuran was added 8 ml of 1 molar solution of lithium aluminum hydride in THF. This was stirred for 1/2 hour and then quenched with 6 ml of saturated ammonium chloride solution. The inorganics were filtered and rinsed with ethyl acetate. The combined organics were then dried over anhydrous magnesium sulfate and concentrated to give a solid. This was twice recrystallized from acetone/hexane to give 1.4 g of an analytically pure powder, mp 135-138°C. EXAMPLE 65 9-Benzylamino-6-methyl-1,2,3,4-tetrahydroacridin-1-ol To a cooled suspension of 3.6 g of 9-benzylamino-3,4-dihydro-6-methylacridin-1(2H)-one in 8⊘ ml of tetrahydrofuran was added 6 ml of 1 M solution of lithium aluminum hydride in THF. This was stirred for 1 hour, and thereafter quenched with 7 ml of saturated ammonium chloride solution. The inorganics were filtered and rinsed with ethyl acetate and the combined organics were dried over anhydrous magnesium sulfate. The resulting solid was triturated with ethyl ether to obtain 3.15 g of a solid, mp 148-153°C. This was recrystallized from toulene (7⊘ ml) to obtain 2.5 g of an analytically pure solid, mp 149-152°C. EXAMPLE 66 9-Benzylamino-6-fluoro-1,2,3,4-tetrahydroacridin-1-ol To a cooled suspension of 4.85 g of 9-benzylamino-3,4-dihydro-6-fluoroacridin-1(2H)-one in 8⊘ ml of tetrahydrofuran was added 7.5 ml of 1 molar solution of lithium aluminum hydride in THF. This was stirred for 1 hour. The reaction was then quenched with 5 ml of saturated ammonium chloride solution. The inorganics were filtered and rinsed with ethyl acetate. The combined organics were dried over anhydrous magnesium sulfate and concentrated to a solid which was triturated with ethyl ether to obtain 3.3 g of a powder, mp 155-162°C. This was recrystallized from ethyl acetate/hexane (12⊘ ml) to obtain 2.4 g of an analytically pure solid, mp 164-166°C. EXAMPLE 67 9-Benzylamino-6-chloro-1,2,3,4-tetrahydroacridin-1-ol In 1⊘⊘ ml of dry THF was added 2.9⊘ g of 9-benzylamino-6-chloro-3,4-dihydroacridin-1(2H)-one. The mechanically stirred solution was cooled with ice under nitrogen and 4.3 ml of 1M lithium aluminum hydride solution in THF was added dropwise over 1⊘ minutes. After 1 hour of stirring at 1⊘°C, the reaction was complete by TLC, so it was quenched with 1 ml of saturated ammonium chloride solution. The inorganic salts were filtered off and the filtrate was evaporated to a solid. The solid was recrystallized from 1:1 dichloromethane/pentane to yield 2.14 g of solid, mp 163°C . EXAMPLE 68 9-Benzylamino-6-trifluoromethyl-1,2,3,4-tetrahydroacridin-1-ol To a cooled solution of 3.5 g of 9-benzylamino-3,4-dihydro-6-trifluoromethylacridin-1(2H)-one in 6⊘ ml of tetrahydrofuran was added 5 ml of 1M solution of lithium aluminum hydride in tetrahydrofuran. This was stirred for 1 hour at ice temperature. The reaction was then quenched with 5 ml of saturated ammonium chloride solution. The inorganics were filtered and rinsed with ethyl acetate, and the combined organics were dried over anhydrous magnesium sulfate. This was concentrated to a solid, mp 153-157°C, which was recrystallized from isopropyl ether to yield 2.⊘ g of an analytically pure powder, mp 156-158°C. EXAMPLE 69 9-(2-Methylbenzylamino)-1,2,3,4-tetrahydroacridin-1-ol 3,4-Dihydro-9-(2-methylbenzylamino)acridin-1(2H)-one (4.15 g) was suspended in 1⊘⊘ ml of THF and chilled with ice-water. 1M lithium aluminum hydride in THF (8.⊘ ml) was added dropwise through a syringe and then the reaction mixture was stirred 3⊘ minutes in the cold. It was quenched by the sequential addition of ⊘.5 ml of water, ⊘.5 ml of 15% sodium hydroxide and 1.5 ml of water. The inorganic salts were filtered and the organic phase was evaporated to obtain an amorphous solid product. Recrystallization from ethyl acetate gave 3.38 g, mp 167-169°C. EXAMPLE 7⊘ 9-(3-Methylbenzylamino)-1,2,3,4-tetrahydroacridin-1-ol 3,4-Dihydro-9-(3-methylbenzylamino)acridin-1(2H)-one (3.7⊘ g) was dissolved in 1⊘⊘ ml of dry THF and chilled in ice-water. 1M lithium aluminum hydride in THF (7.⊘ ml) was added and the reaction stirred 3⊘ minutes in the cold. The reaction mixture was quenched by the sequential addition of ⊘.5 ml of water, ⊘.5 ml of 15% sodium hydroxide and 1.5 ml of water. The inorganic salts were filtered from the reaction mixture and the organic phase was evaporated to an oil. Trituration with ether gave a solid that was recrystallized from ethyl acetate/pentane to obtain 3.22 g, mp 133-134°C. EXAMPLE 71 9-(4-Methylbenzylamino)-1,2,3,4-tetrahydroacridin-1-ol 3,4-Dihydro-9-(4-methylbenzylamino)acridin-1(2H)-one (5.71 g) was dissolved in 1⊘⊘ ml of dry THF, chilled with ice-water, and then 9.⊘ ml of 1M lithium aluminum hydride in THF was added. After 15 minutes the reaction was quenched by the sequential addition of ⊘.4 ml of water, ⊘.4 ml of 15% sodium hydroxide, and 1.2 ml of water. The inorganic salts were filtered off and washed with warm THF and then the combined organic phase was evaporated and the residue recrystallized from dichloromethane-pentane to obtain 4.77 g of analytically pure product, mp 176-178°C. EXAMPLE 72 9-(2-Methoxybenzylamino)-1,2,3,4-tetrahydroacridin-1-ol 3,4-Dihydro-9-(2-methoxybenzylamino)acridin-1(2H)-one (4.⊘ g) was dissolved in 1⊘⊘ ml of dry THF and chilled in ice-water. 1M lithium aluminum hydride in THF (6.5 ml) was added through a syringe. The reaction mixture was stirred 3⊘ minutes in the cold and then an additional 2.⊘ ml of 1M lithium aluminum hydride solution was added. The reaction mixture was quenched by the sequential addition of ⊘.5 ml of water, ⊘.5 ml of 15% sodium hydroxide and 1.5 ml of water. The inorganic salts were filtered from the reaction and the organic phase was evaporated to a gum. Trituration with ether gave a solid (2.95 g). Analytically pure material was obtained by recrystallization from ethyl acetate-pentane, mp 115-117°C. EXAMPLE 73 9-(3-Methoxybenzylamino)-1,2,3,4-tetrahydroacridin-1-ol 3,4-Dihydro-9-(3-methoxybenzylamino)acridin-1(2H)-one (4.⊘ g) was dissolved in 75 ml of dry THF, the solution was chilled with ice-water, and 1M lithium aluminum hydride (6.5 ml) was added dropwise through a syringe. After 3⊘ minutes TLC showed that the reaction was complete, so the reaction was quenched by the successive addition of ⊘.4 ml of water, ⊘.4 ml of 15% sodium hydroxide, and 1.2 ml of water. The inorganic salts were filtered off and the organic phase was evaporated to an oil. Trituration with ether gave a solid that was filtered off and then recrystallized from ether-pentane to give 2.2 g of analytically pure product, mp 123-125°C. EXAMPLE 74 9-(4-Methoxybenzylamino)-1,2,3,4-tetrahydroacridin-1-ol 3,4-Dihydro-9-(4-methoxybenzylamino)acridin-1(2H)-one (4.25 g) was dissolved in 75 ml of dry THF and chilled with ice-water. 1M lithium aluminum hydride in THF (7.⊘ ml) was then added dropwise. After 15 minutes the reaction was quenched by the sequential dropwise addition of ⊘.4 ml of water, ⊘.4 ml of 15% sodium hydride and 1.2 ml of water. The inorganic salts were filtered off, the solvents were evaporated, and the residue recrystallized from dichloromethane-ether to give 3.⊘ g of analytically pure product, mp 163-165°C. EXAMPLE 75 9-(3-Fluorobenzylamino)-1,2,3,4-tetrahydroacridin-1-ol In 1⊘⊘ ml of THF was dissolved 3.⊘⊘ g of 3,4-dihydro-9-(3-fluorobenzylamino)acridin-1(2H)-one. The mechanically stirred solution was cooled in ice under nitrogen and 4.68 ml of 1M lithium aluminum hydride in THF was added dropwise over 15 minutes. After ⊘.5 hour, analysis by TLC indicated the reaction was complete, so it was neutralized with 1 ml of saturated ammonium chloride solution and the resulting salts were filtered. The filtrate was evaporated to an oil which crystallized on trituration with pentane. The solid was filtered and recrystallized from 1:1 dichloromethane/pentane to yield 2.5⊘ g of solid, mp 128°C. EXAMPLE 76 9-(4-Fluorobenzylamino)-1,2,3,4-tetrahydroacridin-1-ol In 1⊘⊘ ml of dry THF was dissolved 3.⊘⊘ g of 3,4-dihydro-9-(4-fluorobenzyl)aminoacridin-1(2H)-one. The mechanically stirred solution was cooled in ice and 4.68 ml of 1M LiAlH₄ in THF was added over 5 minutes. After 1/2 hour the reaction was complete by TLC. The excess hydride was neutralized with 1 ml of saturated ammonium chloride solution and the resulting salts were filtered. The THF filtrate was evaporated to a solid which was recrystallized from 1:1 dichloromethane/pentane to yield 2.47 g of solid, mp 169.5-17⊘°C. EXAMPLE 77 6-Chloro-9-(4-fluorobenzylamino)-1,2,3,4,-tetrahydroacridin-1-ol In 1⊘⊘ ml of dry THF was added 4.⊘6 g of 6-chloro-3,4-dihydro-9-(4-fluorobenzylamino)acridin-1(2H)-one and the mechanically stirred solution was cooled to 1⊘°C under a nitrogen atmosphere. To the reaction was added 5,3 ml of 1M LiAlH₄ in THF over 15 minutes. After 1/2 hour the reaction was complete by TLC analysis, so it was quenched with 1 ml of saturated ammonium chloride solution and the inorganic salts were filtered off. The filtrate was evaporated to a solid which was recrystallized from dichloromethane to yield 3.18 g of solid. The compound went through a crystal structure change at 176-177°C before melting at 187-188°C. EXAMPLE 78 9-(2-Chlorobenzylamino)-1,2,3,4-tetrahydroacridin-1-ol To a cooled suspension of 9-(2-chlorobenzylamino)-3,4-dihydroacridin-1(2H)-one (4.⊘ g) in 75 ml of tetrahydrofuran was added 6.5 ml of 1M solution of lithium aluminum hydride in THF. This was stirred at ice bath temperature for 1.5 hours. The reaction was then quenched with 15 ml of saturated ammonium chloride solution. The salts were filtered, washed with ethyl acetate and the filtrate was dried over anhydrous magnesium sulfate. This was concentrated to a solid which was triturated with ethyl ether and filtered to give 3.8 g of a powder, mp 136-141°C. This was recrystallized from ethyl acetate to give 2.75 g of an analytically pure solid, mp 141-143°C. EXAMPLE 79 9-(3-Chlorobenzylamino)-1,2,3,4-tetrahydroacridin-1-ol To a ice cooled suspension of 9-(3-chlorobenzylamino)-3,4-dihydroacridin-1(2H)-one (3.6 g) in 75 ml of tetrahydrofuran was added a 1 M solution of lithium aluminum hydride in THF (6 ml). This was stirred at ice bath temperature for 45 minutes. The reaction was then quenched with 15 ml of saturated ammonium chloride solution, the precipitates were filtered and washed with ethyl acetate and the organics were dried over anhydrous magnesium sulfate. This was concentrated to a solid which was triturated with ethyl ether to give 3.6 g of a solid, mp 14⊘-142°C. EXAMPLE 80 9-(4-Chlorobenzylamino)-1,2,3,4-tetrahydroacridin-1-ol To a cooled solution of 6.25 g of 9-(4-chlorobenzylamino)-3,4-dihydroacridin-1(2H)-one in 14⊘ ml of tetrahydrofuran was added 1⊘ ml of 1M LiAlH₄ solution in THF. This was stirred at ice bath temperature for 1 hour. The reaction was then quenched with 1⊘ ml of saturated ammonium chloride solution, the inorganics were filtered and washed with ethyl acetate. The combined organics were dried over anhydrous magnesium sulfate and concentrated to a solid. This was recrystallized from ethyl acetate to yield 5.1 g of an analytically pure solid, mp 175.5-177.5°C. EXAMPLE 81 1,2,3,4-Tetrahydro-9-(2-trifluoromethylbenzylamino)-acridin-1-ol In 1⊘⊘ ml of dry THF was dissolved 4.31 g of 3,4-dihydro-9-(2-trifluoromethylbenzylamino)acridin-1(2H)-one and the mechanically stirred solution was cooled to 1⊘°C under nitrogen. To it was added 5.8 ml of 1M LiAlH₄ in THF dropwise over 15 minutes. Within ⊘.5 hour of addition the reaction was complete by TLC, so it was quenched with 1 ml of saturated ammonium chloride and the salts were filtered. The filtrate was evaporated to a solid which was dissolved in dichloromethane. The dichloromethane solution was dried over anhydrous magnesium sulfate and filtered. The filtrate was refluxed and pentane was added to effect crystallization. The crystals were collected from the cooled mother liquor to yield 3.44 g of solid, mp 158-16⊘°C. EXAMPLE 82 6-Fluoro-1,2,3,4-tetrahydro-9-(2-trifluoromethylbenzylamino)acridin-1-ol To a cooled solution of 5.7 g of 3,4-dihydro-6-fluoro-9-(2-trifluoromethylbenzylamino)acridin-1(2H)-one in 8⊘ ml of tetrahydrofuran was added 7.5 ml of 1 molar solution of lithium aluminium hydride in THF. This was stirred for ⊘.5 hour and then quenched with 6 ml of saturated ammonium chloride solution. The inorganics were filtered, rinsed with ethyl acetate and the combined organics were dried over anhydrous magnesium sulfate. This was concentrated to a solid which was triturated with ether to give 5.1 g of a powder. This was twice recrystallized from ethyl acetate/hexane to give 3.1 g of analytically pure crystals, mp 149-153°C. EXAMPLE 83 1,2,3,4,-Tetrahydro-9-(3-trifluoromethylbenzylamino)acridin-1-ol In 1⊘⊘ ml dry THF was dissolved in 3.86 g of 3,4-dihydro-9-(3-trifluoromethylbenzyl)aminoacridin-1(2H)-one. The solution was stirred mechanically under nitrogen and cooled in ice. To it was added 5.2 ml of 1M LiAlH₄ in THF dropwise. After stirring an additional ⊘.5 hour, the reaction was complete. It was neutralized with 1 ml of saturated ammonium chloride and the salts were filtered off. The THF filtrate was evaporated to an oil which solidified upon trituration with pentane. The solid was recrystallized from 1:1 dichloromethane/pentane to yield 3.12 g of solid, mp 154-155°C. EXAMPLE 84 1,2,3,4-Tetrahydro-9-(4-trifluoromethylbenzylamino)acridin-1-ol In 1⊘⊘ ml of dry THF was dissolved 2.49 g of 3,4-dihydro-9-(4-trifluoromethylbenzylamino)acridin-1(2H)-one. The mechanically stirred solution was cooled under nitrogen to 1⊘°C and 3.4 ml of 1M LiAlH₄ in THF was added dropwise over 1⊘ minutes. After 1/2 hour of stirring, the reaction was complete. It was neutralized with 1 ml of saturated ammonium chloride solution and the resulting salts were filtered. The filtrate was evaporated to a solid which was recrystallized from 1:1 dichloromethane/pentane to yield 1.91 g of solid, mp 174-176°C. EXAMPLE 85 9-[(2,3,4,5,6-Pentafluorobenzyl)amino]-1,2,3,4-tetrahydroacridin-1-ol, fumarate To a cooled solution of 3.8 g of 3,4-dihydro-9-[(2,3,4,5,6-pentafluorobenzyl)amino]acridin-1(2h)-one in 6⊘ ml of tetrahydrofuran was added 5 ml of 1M solution of lithium aluminum hydride in tetrahydrofuran. After 1 hour, an additional 1 ml of the LiAlH₄ solution was added. This was stirred for ⊘.5 hour and then quenched with 5 ml of saturated ammonium chloride solution. The inorganics were filtered and rinsed with warm THF. The filtrate was diluted with ethyl acetate and dried over anhydrous magnesium sulfate. This was then concentrated to a solid which was triturated with diethyl ether to give 2.25 g of a powder, mp 2⊘2-2⊘7°C decomp. The free base was dissolved in 15⊘ ml of ethanol and 5⊘ ml of methanol and acidified with an ethanolic fumaric acid solution. The resulting crystals were collected and dried to give 2.15 g of a solid, mp 214-216°C decomp. EXAMPLE 86 9-(4,4-Diphenylbutyl)amino-1,2,3,4-tetrahydroacridin-1-ol In 3⊘ ml of dry THF was dissolved 3.⊘⊘ g of 3-4-dihydro-9-(4,4-diphenylbutyl)aminoacridin-1(2H)-one and the mechanically stirred solution was cooled in an ice bath under nitrogen atmosphere. To the solution under nitrogen was added 6.48 ml of 1M LiAlH₄ in THF. Within ⊘.5 hour after addition the reaction was complete by TLC. The reaction was neutralized with 1 ml of saturated ammonium chloride solution and the inorganics were filtered off. The filtrate was evaporated to an oil and the oil was triturated with 3⊘ ml of 1⊘:1 ether/acetone to yield 2.22 g of solid, mp 147-148°C. This sample was combined with a 1.⊘ g sample of an identical previous run and recrystallized from acetone to yield 2.87 g of powder, mp 146-148°C. EXAMPLE 87 9-[4,4-Bis(3-fluorophenyl)butylamino]-1,2,3,4-tetrahydroacridin-1-ol, hemi-fumarate To a cooled solution of 5.3 g of 9-[4,4-bis(3-fluorophenyl)butylamino]-3,4-dihydroacridin-1(2H)-one in 1⊘⊘ ml of tetrahydrofuran was added 7 ml of 1M solution of lithium aluminium hydride in THF. This was stirred for 2 hours and then quenched with 5 ml of saturated ammonium chloride solution. This was then diluted with ethyl acetate, filtered and the inorganics were rinsed with ethyl acetate. The combined organics were then dried over anhydrous magnesium sulfate and passed through a column of magnesium silicate (ethyl acetate). This gave a fibrous semi-solid which was dissolved in ethanol, acidified with an ethanolic solution of fumaric acid and diluted with ethyl ether. The resulting crystals were collected and dried to give 2.35 g of a solid, mp 18⊘-181°C decomp. EXAMPLE 88 9-[4,4-Bis(4-fluorophenyl)butylamino]-1,2,3,4-tetrahydroacridin-1-ol To a cooled solution of 4.2 g of 3,4-dihydro-9-[4,4-bis(4-fluorophenyl)butylamino]acridin-1(2H)-one in tetrahydrofuran was added 5 ml of 1M solution of lithium aluminum hydride in tetrahydrofuran. This was stirred for ⊘.5 hour at ice bath temperature. The reaction was then quenched with 5 ml of saturated ammonium chloride solution, the inorganics were filtered and rinsed with ethyl acetate and the combined organics were dried over anhydrous magnesium sulfate. This was concentrated to a solid which was triturated with ethyl ether to give 3.4 g of a solid, mp 155-158°C. This was recrystallized from isopropyl ether/methanol (15:1) to yield 2.15 g of an analytically pure solid, mp 157-159°C. EXAMPLE 89 9-(3-Phenoxypropylamino)-1,2,3,4-tetrahydroacridin-1-ol In 1⊘⊘ ml of dry THF was dissolved 2.47 g of 3,4-dihydro-9-(3-phenoxypropyl)aminoacridin-1(2H)-one. The mechanically stirred solution was cooled in ice under nitrogen and 3.6 ml of 1M LiAlH₄ in THF was added dropwise over 5 minutes. After ⊘.5 hour the reaction was complete by TLC. The reaction was neutralized with 1 ml of saturated ammonium chloride solution and the inorganic salts were filtered off. The filtrate was evaporated to an oil which solidified when triturated with pentane. The solid was recrystallized from 1:1 dichloromethane/pentane to yield after drying 2.17 g of product, mp 138-14⊘°C. EXAMPLE 9⊘ 9-[[2-[Bis(4-fluorophenyl)methoxy]ethyl]amino]-1,2,3,4-tetrahydroacridin-1-ol To a cooled solution of 5.55 g of 3,4-dihydro-9-[[2[bis(4-fluorophenyl)methoxy]ethyl]amino]acridin-1(2H)-one in 1⊘⊘ ml of tetrahydofuran was added 6.5 ml of 1M solution of lithium aluminum hydride in tetrahydrofuran. This was stirred for 1 hour at ice bath temperature. The reaction was then quenched with 5 ml of saturated ammonium chloride solution, and the inorganics were filtered and washed with ethyl acetate. The combined organics were then dried over anhydrous magnesium sulfate. This was concentrated to a solid which was triturated with diethyl ether to give 3.45 g of a solid, mp 18⊘-183°C. EXAMPLE 91 9-[4-(Benzyloxy)benzylamino]-1,2,3,4-tetrahydroacridin-1-ol To a cooled suspension of 4.75 g of 3,4-dihdyro-9-[4(benzyloxy)benzylamino]acridin-1(2H)-one in 75 ml of tetrahydrofuran was added 6 ml of 1M solution of lithium aluminum hydride in tetrahydofuran. This was stirred for 1 hour. The reaction was then quenched with 5 ml of saturated ammonium chloride solution and the inorganics were filtered and rinsed with ethyl acetate. This was dried over anhydrous magnesium sulfate and concentrated to a solid which was triturated with ethyl ether and recrystallized from acetone to give 1.65 g of an analytically pure powder, mp 172-175°C. EXAMPLE 92 9-[(2-Thienyl)methylamino]-1,2,3,4-tetrahydroacridin-1-ol, fumarate To a cooled solution of 4.⊘ g of 3,4-dihydro-9-[(2-thienyl)methylamino]acridin-1(2H)-one in 75 ml of tetrahydrofuran was added 7 ml of 1M solution of lithium aluminum hydride in tetrahydrofuran. This was stirred for 1 hour. The reaction was then quenched with 5 ml of saturated ammonium chloride solution, and the inorganics were filtered and rinsed with ethyl acetate. The organics were then dried over anhydrous magnesium sulfate and concentrated to a solid which was triturated with ethyl ether to give 3.3 g of a solid, mp 149-154°C. This solid was recrystallized from ethyl acetate and the resulting solid was dissolved in a mixture of 1⊘⊘ ml isopropanol and 25 ml of methanol and the solution was acidified with a isopropanolic solution of fumaric acid. The resulting solid was filtered and dried to give 2.6 g of an analytically pure solid, mp 183-184°C decomp. EXAMPLE 93 9-Amino-1,2,3,4-tetrahydro-cyclopenta[b]quinolin-1-ol, maleate To a cooled suspension of 3.2 g of 9-amino-2,3-dihydrocyclopenta[b]quinolin-1-one in 1⊘⊘ ml of tetrahydrofuran was added 17 ml of 1 M solution of lithium aluminum hydride in THF. This was stirred for 2 hours and thereafter quenched with 12 ml of saturated ammonium chloride solution. This was diluted with ethyl acetate and filtered. This solution was allowed to stand overnight during which time crystals were formed. These were filtered and the filtrate was concentrated to a solid which was triturated with isopropanol/ethyl ether to give overall 1.9 g of a solid, mp 195-2⊘5°C decomp. This was suspended in 1⊘⊘ ml of isopropanol and 1.27 g of maleic acid. From this, a solution resulted which was filtered and diluted with 5⊘ ml of ethyl ether. The resulting crystals were filtered and recrystallized from tetrahydrofuran/methanol/ethyl ether (4:1:4) to give 1.5 g of an analytically pure solid, mp 16⊘-162°C d.

Claims: A compound of the formula wherein n is 1, 2 or 3; X is hydrogen, C₁-C₆-alkyl, C₁-C₆-alkoxy, halogen, hydroxy ,nitro, trifluoromethyl, NHCOR₂ where R₂ is C₁-C₆-alkyl, or NR₃R₄ where R₃ and R₄ are independently hydrogen or C₁-C₆-alkyl; R is hydrogen or C₁-C₆-alkyl; R₁ is hydrogen, C₁-C₆-alkyl, di-C₁-C₆-alkylamino-C₁-C₆-alkyl, phenyl-C₁-C₆-alkyl, diphenyl-C₁-C₆-alkyl, phenyloxy-C₁-C₆-alkyl or di(phenyl)-methoxy-C₁-C₆-alkyl, wherein the phenyl group is unsubstituted or has 1, 2 or 3 substituents each of which being independently C₁-C₆-alkyl, C₁-C₆-alkoxy, halogen, hydroxy, CF₃, phenoxy or benzyloxy, or the phenyl group is substituted with four or five fluorine, chlorine or bromine atoms, or R₁ is furyl-C₁-C₆-alkyl, furyloxy-C₁-C₆-alkyl, thienyl-C₁-C₆-alkyl or thienyloxy-C₁-C₆-alkyl, Y is C=O or CR₅OH where R₅ is hydrogen or C₁-C₆-alkyl; Z is CH₂ or C=CR₆R₇ where R₆ and R₇ are independently hydrogen or C₁-C₆-alkyl; or Y and Z taken together is CR₅=CH where CR₅ and CH correspond to Y and Z respectively; an optical antipode thereof, or a pharmaceutically acceptable acid addition salt thereof. A compound as defined in claim 1, where n is 2. A compound as defined in claim 2, where R is hydrogen and R₁ is hydrogen, C₁-C₆-alkyl, C₁-C₆-alkoxy, phenyl-C₁-C₆-alkyl or diphenyl-C₁-C₆-alkyl, where the phenyl group is unsubstituted or substituted as indicated in claim 1. A compound as defined in claim 3 where Z is -CH₂ and Y is -C=O or CHOH or Y and Z together form the -CH=CH-radical. The compound as defined in claim 1 which is 9-amino-3,4-dihydroacridin-1(2H)-one or a pharmaceutically acceptable acid addition salt thereof. The compound as defined in claim 1 which is 3,4-dihydro-9-(4,4-diphenylbutyl)-aminoacridin-1(2H)-one or a pharmaceutically acceptable acid addition salt thereof. The compound as defined in claim 1 which is 9-[4,4-bis(3-fluorophenyl)butylamino]-3,4-dihydro-acridin-1(2H)-one or a pharmaceutically acceptable acid addition salt thereof. The compound as defined in claim 1 which is 9-amino-1,2,3,4-tetrahydro-6-trifluormethyl-acridin-1-ol or a pharmaceutically acceptable acid addition salt thereof. The compound as defined in claim 1 which is 1,2,3,4-tetrahydro-9-(2-trifluormethylbenzyl)amino-acridin-1-ol or a pharmaceutically acceptable acid addition salt thereof. The compound as defined in claim 1 which is 9-amino-1,2,3,4-tetrahydroacridin-1-ol or pharmaceutically acceptable acid addition salt thereof. The compound as defined in claim 1 which is 9-benzylamino-1,2,3,4-tetrahydroacridin-1-ol or a pharmaceutically acceptable acid addition salt thereof. A pharmaceutical composition comprising as active ingredient a compound of the formula I or a pharmaceutically acceptable acid addition salt thereof as defined in claim 1 in association with a pharmaceutically acceptable carrier. Use of a compound as defined in claim 1 for the preparation of a medicament useful in the treatment of various memory dysfunctions characterized by decreased cholinergic function. A compound of the formula II wherein n is 1, 2 or 3 and X is as defined in claim 1. A process for the preparation of a compound as defined in claim 1 which comprises a) cyclizing a compound of the formula II wherein X and n are as defined in claim 1, in the presence of a metallic halide, to obtain a compound of the formula IV b) optionally reacting a compound of the formula IV wherein X is as defined in claim 1 except hydroxy, amino, C₁-C₆-alkylamino or the group NHCOR₂ with a compound of the formula R₁W wherein R₁ is as defined in claim 1 except hydrogen and W is Cl, Br, I or the radical OSO₃CH₃, to form a compound of the formula V wherein R₁ is as defined in claim 1 except hydrogen, c) optionally reacting a compound of the formula V wherein X is as defined in claim 1 except hydroxy, amino, C₁-C₆-alkylamino or the group NHCOR₂, with a compound RW where R is as defined in claim 1 except hydrogen and W is as defined in claim 1, to form a compound of the formula VI d) optionally subjecting a compound of the formulae V or VI where X is C₁-C₆-alkoxy to a cleavage reaction to form a compound of the formulae V or VI where X is hydroxy, e) optionally nitrating a compound or the formulae V or VI where X is hydrogen to form a compound of the formulae V or VI where X is the nitro group, f) optionally hydrogenating a compound of the formulae V or VI where X is the nitro group to form a compound of the formulae V or VI where X is the amino group, g) optionally acylating a compound of the formula V or VI where X is the amino group to form a compound of the formulae V or VI where X is the -NHCOR₂ radical, h) optionally reacting a compound of the formulae V or VI where X is the -NHCOR₂ radical with a C₁-C₆-alkyl iodide or bromide to form a compound of the formulae V or VI where X is the group and hydrolyzing this compound to form a compound of the formulae V or VI where X is C₁-C₆-alkylamino, j) optionally reducing a compound of the formula XII wherein R, R₁ and X are as defined in claim 1, with a compound of the formula where R₆ and R₇ are as defined in claim 1, to form a compound of the formula and further decomposing the intermediate product to obtain a compound of the formula m) optionally dehydrating a compound of the formula where R₅ is hydrogen or C₁-C₆-alkyl, and R, R₁ and X are as defined in claim 1 with the proviso that X is not -NHCOR₂ or -NO₂, to obtain a compound of the formula where R, R₁, R₅ and X are as defined in claim 1, and n) optionally reacting a compound of the formula where R, R₁, R₆, R₇ and X are as defined in claim 1 with the proviso that X is not NO₂ or -NHCOR₂ with (i-butyl)₂AlH or R₅Li, R₅ being C₁-C₆-alkyl to obtain a compound of the formula where R, R₁, R₅, R₆,R₇ and X are as defined in claim 1. A process as defined in claim 15 where n is 2. Claims for the following Contracting State: AT A process for the preparation of a compound of the formula wherein n is 1, 2 or 3; X is hydrogen, C₁-C₆-alkyl, C₁-C₆-alkoxy, halogen, hydroxy ,nitro, trifluoromethyl, NHCOR₂ where R₂ is C₁-C₆-alkyl, or NR₃R₄ where R₃ and R₄ are independently hydrogen or C₁-C₆-alkyl; R is hydrogen or C₁-C₆-alkyl; R₁ is hydrogen, C₁-C₆-alkyl, di-C₁-C₆-alkyl-amino-C₁-C₆-alkyl, phenyl-C₁-C₆-alkyl, diphenyl-C₁-C₆-alkyl, phenyloxy-C₁-C₆-alkyl or di(phenyl)-methoxy-C₁-C₆-alkyl, wherein the phenyl group is unsubstituted or has 1, 2 or 3 substituents each of which being independently C₁-C₆-alkyl, C₁-C₆-alkoxy, halogen, hydroxy, CF₃, phenoxy or benzyloxy, or the phenyl group is substituted with four or five fluorine, chlorine or bromine atoms, or R₁ is furyl-C₁-C₆-alkyl, furyloxy-C₁-C₆-alkyl, thienyl-C₁-C₆-alkyl or thienyloxy-C₁-C₆-alkyl, Y is C=O or CR₅OH where R₅ is hydrogen or C₁-C₆-alkyl; Z is CH₂ or C=CR₆R₇ where R₆ and R₇ are independently hydrogen or C₁-C₆-alkyl; or Y and Z taken together is CR₅=CH where CR₅ and CH correspond to Y and Z respectively; an optical antipode thereof, or a pharmaceutically acceptable acid addition salt thereof, which comprises a) cyclizing a compound of the formula II wherein X and n are as defined above, in the presence of a metallic halide, to obtain a compound of the formula IV b) optionally reacting a compound of the formula IV wherein X is as defined above except hydroxy, amino, C₁-C₆-alkylamino or the group NHCOR₂ with a compound of the formula R₁W wherein R₁ is as defined above except hydrogen and W is Cl, Br, I or the radical OSO₃CH₃, to form a compound of the formula V wherein R₁ is as defined above except hydrogen, c) optionally reacting a compound of the formula V wherein X is as defined above except hydroxy, amino, C₁-C₆-alkylamino or the group NHCOR₂, with a compound RW where R is as defined above except hydrogen and W is as defined above, to form a compound of the formula VI d) optionally subjecting a compound of the formulae V or VI where X is C₁-C₆-alkoxy to a cleavage reaction to form a compound of the formulae V or VI where X is hydroxy, e) optionally nitrating a compound or the formulae V or VI where X is hydrogen to form a compound of the formulae V or VI where X is the nitro group, f) optionally hydrogenating a compound of the formulae V or VI where X is the nitro group to form a compound of the formulae V or VI where X is the amino group, g) optionally acylating a compound of the formula V or VI where X is the amino group to form a compound of the formulae V or VI where X is the -NHCOR₂ radical, h) optionally reacting a compound of the formulae V or VI where X is the -NHCOR₂ radical with a C₁-C₆-alkyl iodide or bromide to form a compound of the formulae V or VI where X is the group and hydrolyzing this compound to form a compound of the formulae V or VI where X is C₁-C₆-alkylamino, j) optionally reducing a compound of the formula wherein R, R₁ and X are as defined above, with a compound of the formula where R₆ and R₇ are as defined above, to form a compound of the formula and further decomposing the intermediate product to obtain a compound of the formula m) optionally dehydrating a compound of the formula where R₅ is hydrogen or C₁-C₆-alkyl, and R, R₁ and X are as defined above with the proviso that X is not -NHCOR₂ or -NO₂, to obtain a compound of the formula where R, R₁, R₅ and X are as defined, and n) optionally reacting a compound of the formula where R, R₁, R₆, R₇ and X are as defined above with the proviso that X is not NO₂ or -NHCOR₂ with (i-butyl)₂AlH or R₅Li, R₅ being C₁-C₆-alkyl to obtain a compound of the formula where R, R₁, R₅, R₆R₇ and X are as defined. A process as defined in claim 1 where n is 2. A process as defined in claim 1, wherein R is hydrogen, and R₁ is hydrogen, C₁-C₆-alkyl, C₁-C₆-alkoxy, phenyl-C₁-C₆-alkyl or diphenyl-C₁-C₆-alkyl, where the phenyl group is unsubstituted or substituted as indicated in claim 1. A process as defined in claim 3 where Z is -CH₂ and Y is or -CHOH or Y and Z together form the -CH=CH-radical. The process as defined in claim 1 wherein 9-amino-3,4-dihydroacridin-1(2H)-one or a pharmaceutically acceptable acid addition salt thereof is prepared. The process as defined in claim 1 wherein 3,4-dihydro-9-(4,4-diphenylbutyl)-aminoacridin-1(2H)-one or a pharmaceutically acceptable acid addition salt therof is prepared. The process as defined in claim 1 wherein 9-[4,4-bis(3-fluorophenyl)butylamino]-3,4-dihydro-acridin-1(2H)-one or a pharmaceutically acceptable acid addition salt therof is prepared. The process as defined in claim 1 wherein 9-amino-1,2,3,4-tetrahydro-6-trifluoromethyl-acridin-1-ol or a pharmaceutically acceptable acid addition salt thereof is prepared. The process as defined in claim 1 wherein 1,2,3,4-tetrahydro-9-(2-trifluormethylbenzyl)amino-acridin-1-ol or a pharmaceutically acceptable acid addition salt thereof is prepared. The process as defined in claim 1 wherein 9-amino-1,2,3,4-tetrahydroacridin-1-ol or a pharmaceutically acceptable acid addition salt thereof is prepared. The process as defined in claim 1 wherein 9-benzylamino-1,2,3,4-tetrahydroacridin-1-ol or a pharmaceutically acceptable acid addition salt thereof is prepared. Use of a compound as defined in claim 1 for the preparation of a medicament useful in the treatment of various memory dysfunctions characterized by decreased cholinergic function.

Inventors: PIERRAT, FRANK A., SHUTSKE, GREGORY M.
Applicants: HOECHST-ROUSSEL PHARMACEUTICALS INCORPORATED
Application year: 1985
Main classification: C07D219
IPC codes: C07C67, C07D221, C07D219, C07C255, C07C253, C07D409, A61K31