COMPOUNDS FOR THE TREATMENT OF ALZHEIMER'S DISEASE

Abstract: Compounds of formula (I) are of use in treating Alzheimer's disease.

Description: Compounds for the Treatment of Alzheimer's Disease The present invention is directed to galanthamine- analogues.and their preparation and use for treatment of Alzheimer's disease. United States Patent No. 4,663,318 issued on May 5, 1987 describes the use of galanthamine for the treatment of Alzheimer's disease and related dementias. Published European Patent Application 236684 describes the use of galanthamine and certain analogues for the treatment of Alzheimer's disease and related dementias, such analogues have the formula: wherein Q 1 is methoxy, ethoxy, lower al anoyloxy or oxy, Q 2 is hydrogen, methoxy, ethoxy or lower alkanoyloxy and 3 is straight or branched chain alkyl group, or cycloalkyl alkyl group, allyl or substituted lower alkyl phenyl and analogues thereof wherein hydrogen atoms are replaced by chloro or fluoro atoms. Without wishing to be bound by any theory, we now believe that the activity of galanthamine probably stems from the fact that a hydrogen bond between the hydroxyl group and the oxygen of the furan ring helps to stabilize its cyclohθxene ring in a boat rather th n .a .qhair configuration: The literature shows the epigalanthamine wherein the hydroxy group is in the equatorial position so that hydrogen bond stabilization of structure is not possible has an anti- cholinesterasβ activity of only 10% of galanthamine. (Chemical Abstracts Vol. 77 Abstract 109461s) A number of galanthamine analogs occur naturally or have been obtained from natural products including the following compounds described in the text book The Alkaloids (edited by published by , the Edition) : Narwedine: (also referred to sometimes as galanthaminone) Narwedine has been reported to have weak anticurare activity at 3 mg/kg (Chemical Abstracts Vol. 78 Abstract 131941r) and to have cholinergic effects on respiration an d heart activity 50-80% lower than galanthamine (Chemical Abstracts Vol. 80 Abstract 103864r) , Schmidt et al in Aσta Biol Med Ger (7) 402-410 (1961) report that the anticholinesterase activity of Narwedene is less than 1% of that of galanthamine. (-) N-demethyl galanthamine: Galanthamine O methyl ether: Childanthine: \ Lycoramine: cH< It has been reported that the concentration of lycoramine required to stimulate EEG - recorded activity is about five times that required for galanthamine (Chemical Abstracts Vol. 62 Abstract 15306e) . Deoxy lycoramine Habranthine: and N-mesityl and N-benzyl derivatives of galanthamine. Reference is also made to compounds of the formulae: so* Ct ~ ** The latter compound has been reported to have activity similar to that of galanthamine (J Chem Soc (C) 1043 (1971) An earlier edition of this book had also referred to (+) N-demβthyl dihydrogalanthamine of the formula: H N-demethyl dihydrogalanthamine is described by Kametani et al in J. Heterocyclic Chemistry 1973 10(1) 35-7. The same paper also refers to galanthamine 0, N diacetate Leucotamine and its O-methyl and O-methyl acetic acid ester are described by Kobayashi et al in Chem. Pharm. Bull. 3_3_ p 5258 (1985). O-Demethyldihydrogalanthamine (also known as 0- demethyl lycoramine) and O-demethyl galanthamine (sanguinine) are described by Kobayashi et al in Chem. Phara. Bull. 23. 3433-3436 (1980). A bromo-narwβdinβ of the formula: is described as an intermediate in the synthesis of galanthamine by Kametani et al in Chem. Comm. 1969 p. 425 and J. Chem. Soc. (C) (1969) 2602. Chemical Abstracts H 14727g Chem Pharm Bull 1 1012-20 (1964) describes the production of compounds of the formula: wherein R may be hydrogen, methyl or ethyl. Chemical Abstracts 8JL 638193 describes n.m.r. studies on dihydrogalanthamine and its acetic acid esters. Shimizu et al in Heterocycles 1977 8. pages 277-82 (abstracted in Chemical Abstracts 8_8 136821t) describe certain narwedine derivatives used as intermediates having the following formulae: Irwin and Smith in Arch Int. Pharmacodyn 1960 CXXLII pages 3-14 et seq. described the cholinesterase activity of galanthamine and some of its analogues including lycoramine acetate methiodide, neopin methiodide (both of which were ineffective) and deoxydemethyl lycoramine methiodide (which demonstrated good activity) and deoxylycoramine (which exhibited some activity) . It was hypothesized that the presence of a free hydroxy group in the cyclohexane ring conferred activity on the molecule since the acetylation of this group led to a drop in activity. In J Pharmacol & Exptl Therap Irwin, Smith and Hein expanded on the work just described and reported that replacement of the hydroxyl group of deoxydemethyl lycoramine methiodide by a carbamate group resulted in useful pharmacological activity. Subsequently, In Irwin and Hine J Pharmacol & Exptl Therap (196) Vol. 136 p 20) described the activity of a number of carbamates including deoxydemethyl lycoramine carbamate on cholinesterase activity in rat brain. Subsequently, Somers et al in Neurology H p. 543 reported that some of Irwin's compounds were useful in treating yasthenia gravis. Detailed Description of the Invention The present invention relates to the use of compounds of the formula I to treat Alzheimer's disease and related dementias £ wherein the broken line represents an optionally present double bond in one of the two portions shown, R^ and R2 are each selected independently from the group consisting of hydrogen, hydroxyl, amino or alkylamino, cyano, sulfhydryl, alkoxy preferably of 1-6 carbon atoms, alkylthio, aryloxy, arylthio, R 5 -substituted aryloxy, R 5 -substituted arylthio, aralkoxy, aralkylthio, R 5 -substituted aralkoxy, Rs-substituted aralkylthio, aryloxymethyl, R5-substituted aryloxymethyl, alkanoyloxy, hydroxy-substituted alkanoyloxy, benzoyloxy, R5- substituted benzoyloxy, aryloxy earbonyl and Rs-substituted aryloxy earbonyl, R^ may also by alkyl of up to 14 carbon atoms, a mono or dialkyl or aryl carba yl group or hydroxy methyl, R2 may also be carboxymethyl provided that at least one of Ri and 2 is hydroxy, amino or alkylamino unless R 7 or β is hydroxymethyl, R3 is hydrogen, straight or branched chain alkyl, preferably of 1-6 carbon atoms, cycloalkyl methyl, alkylphenyl, R 5 -substituted alkylphenyl, heterocyclyl such as ø - or β-furyl, ø r or β-thienyl or thenyl, pyridyl, pyrazinyl or pyrimidyl groups, alkyl heterocyclyl and R'-substituted heterocyclyl, where R' is alkyl or alkoxy each 4 is independently selected from hydrogen, hydroxyl, sulfhydryl, alkyl, aryl, aralkyl, alkoxy, thioalkoxy, aryloxy, thioaryloxy, alkarloxy, thioalkaryloxy, nitro, amino, N-alkylamino, N-arylamino, N-alkarylamino, fluoro, chloro, bromo iodo and trifluoromethyl, and R 5 is selected from the same groups as R 4 , Rg is hydrogen, halo, tri luoromethyl or alkyl of 1 to 4 carbon atoms, R7 is selected from the same groups as R4 or may be hydroxy alkyl of 1-2 carbon atoms, 3 is hydrogen or hydroxymethyl, Rg is hydrogen alkyl of 1 to 6 carbon atoms, phenyl or benzyl, or when R 2 is hydroxyl Rg may be a moiety of formula I wherein. R Q is hydrogen and EL is a linking bond; or R 2 and Rg may jointly form a semi carbazone, X is oxygen or NR.-, Y is nitrogen or phosphorus, preferably nitrogen, and mβthylenedioxy derivatives thereof with the proviso that when X iβ 0, 3 iβ not methyl when R^ iβ methoxy, R 2 iβ hydroxy, and all R 4 are hydrogen or a pharmaceutically- accβptablβ acid addition salt thereof. When there is no unsaturation in the 1,2 carbon bond, R 2 iβ preferably oriented axially to the cyclohexane ring. Preferably the aryl groups are phenyl groups, the aryloxy groups are phenoxy groups, the aralkyl groups are benzyl groups and the aralkyloxy groups are benzyloxy groups. Preferred compounds include those wherein R 1 and R 2 are each selected from wherein R is alkyl 1-6 carbon atoms or phenyl or R 5 - subβtituted phenyl or benzyl or R 5 -βubβtituted benzyl, wherein χo i» hydrogen, alkyl or alkoxy, R 3 iβ -H, or branched on linear alkyl or wherein n is 3, wherein ^o s as defined above where Z is O, S , or NH or Xxis oxygexn and Y is nitrogen. When used herein the term "lower alkyl" means alkyl of 1-6 carbon atoms, preferably 1-4 carbon atoms, most commonly methyl or ethyl. One class of compounds according to the present invention are those of the formula: K wherein R 1 is as defined above, preferably hydroxy, lower alkoxy, aryloxy, R 5 substituent aryloxy, benzyloxy or R 5 substituted benzyloxy, amino, alkyl amino or an alkyl or aryl carba yl group. For example, such compounds include O-demethyl, N- demethyl galanthamine; O-βthyl, O-demethyl, N-demethyl galanthamine; O-phenyl, O-demethyl, N-demethyl galanthamine; and O-benzyl, O-demethyl galanthamine. Useful carbamates may include phenyl carbamyl O-demethyl, N-demthyl galanthamine; mono o - naphthyl carbamyl O-demthyl N-demethyl galanthamine and dimethyl carbamyl O-demethyl, N-demethyl galanthamine. A second class are those of the formula: wherein R 2 is hydroxy, lower alkoxy, arloxy, R 5 substituted arloxy benzyloxy or R 5 substituted benzyloxy or an alkyl or aryl carbamyl group and R 3 is hydrogen or alkyl of 1-6 carbon atoms such as methyl or ethyl, methyl cyclopropyl or benzyl or R 5 -substituted benzyl. Such compounds include O-demethyl galanthamine; O-demethyl galanthamine; O-methyl ether; O- demethyl galanthamine; O-ethyl ether; O-demethyl galanthamine, O-benzyl ether; O-demethyl galanthamine, phenyl and O-demethyl N-demethyl galanthamine, < -naphthyl carbamates; O-demethyl galanthamine dimethyl carbamate and O-dimethyl galanthamine diethy1 carbamate wherein the carbamyl group iβ bonded to the oxygen of the cyclohexene ring, and the corresponding N- demethyl and N-demethyl N-ethyl and N-demethyl N-cyclopropyl methyl and N-demethyl N-benzyl compounds. X' third class of compounds comprises those of the formula: wherein R 1 , R 2 and R 3 are as defined above, R 1 typically being hydroxy, lower alkoxy, benzyloxy or R 5 substituted benzyloxy, amino alkylamino or alkyl or aryl carbamyl, R 2 is hydroxy, lower alkoxy, arloxy, benzyloxy or an alkyl or aryl carbamyl group but is preferably hydroxy and R 3 is typically hydrogen, methyl, ethyl, cyclopropyl methyl or benzyl. Such compounds include, for example, O-demethyl lycoramine; N-demethyl, O-demethyl lycoramine; N-demethyl N- ethyl lycoramine; N-demethyl N-cyclopropylmethyl lycoramine; N-demethyl N-benzyl lycoramine; O-demethyl lycoramine ethyl ether; deoxy O-demethyl lycoramine; O-deoxy demethyl lycoramine, benzyl ether and dimethyl and phenyl carbamyl analogs of such compounds. A further class comprising compounds of the formula: wherein R 3 is selected from hydrogen, lower alkyl, σyσloalkyl methyl or benzyl. Compounds of the above formula I where R 2 is hydroxyl and Rg is a moiety of formula I wherein Rg is hydrogen and R 2 is a linking bond are compounds in which the structure of formula I has linked at ring position 2 a hydroxyl group and a second formula I structure wherein R is a bond linking the second formula I structure to said position 2 of the first and in said second formula I structure, R g is hydrogen. Such compounds may be made by reacting a compound of formula I wherein R 2 is hydroxyl to convert the hydroxyl to a halide, reacting the halide to form a Grignard compound, and reacting the latter with a galanthamine ketone. Useful compounds may include the following: GALANTMAMINS ANALOG! Many compounds of the present invention may be obtained by effecting suitable conversions of galanthamine. Galanthamine has the structure: Compounds wherein R^ is other than methoxy can be obtained from galanthamine by demethylation to the corresponding phenol and, if desired, effecting subsequent conversion thereon. Demethylation may be effected with iodotrimethylsilane in accordance with the method described by M.E. Jung and M.A. Lyster in J. Org. Chem. 4 3761 (1977) . Reaction with iodotrimethylsilane may be effected in any convenient solvent, for example, chloroform at moderate temperatures (typically 25-40°C) for several hours (e.g. 12-20 hours) to cleave the methyl group. The phenol obtained by this reaction may be employed itself or used as an intermediate for the production of other active compounds. If it is desired to avoid effecting the same reactions at the allyliσ hydroxy group in the C ring as are to take place at the phenol group that is produced by demethylation of the A ring when carrying out further interconversions, it is desirable to protect the allylic hydroxyl group. Suitable protection can be effected by converting the allylic hydroxyl group to its tetrahydropyranyl ether or 4-methoxytetra-hydropyranyl ether. Such ethers can be formed by reaction with dihydropyran or 4- methoxytetrahydropyran in a solvent such as dichloromethane at room temperature in the presence of a strong organic acid such as p-toluenesulfoniσ acid. When desired, the protection groups can be removed, the tetrahyropyranyl group, for example, by treatment with ethanol and Dowex-50 WX8 and the -methoxytetrahydropyranyl group by reaction with very dilute (e.g., 0.01N) hydrochloric acid. The phenolic group obtained by demethylation of the methoxy group of galanthamine may readily be converted into an alkali metal salt by reaction with sodium or potassium hydroxide or reaction with sodium hydride in tetrahydrofur n. The salt so obtained may be "alkylated" by reaction with an appropriate alkyl, aryl, alkaryl or R 5 -substituted aryl or alkaryl or heterocyclyl or Rs-substituted heterocyclyl halide to produce a compound wherein R^ is alkoxy (other than methoxy) , aryloxy, alkaryloxy, Rs-substituted aryloxy, R5- substituted alkoxy or heterocyclyl or R 5 -substituted heterocyclyl. The reaction with the halide is typically run with excess halide in the absence of solvent or in a solvent such as dimethyl formamide or dimethylsulfoxide. For less reactive halides, the presence of a silver oxide catalyst may be desirable. Reaction of the phenolic group with an isocyanate can be used to introduce a monoalkyl or monoaryl carbamyl group. Dialkyl or diaryl carbamates may be obtained [by] from the mono alkyl or aryl carbamates by reaction with sodium hydride and an alkyl or aryl iodide. For example, the dimethyl carbamate can be obtained by reaction of the hydroxy group with methyl isocyanate followed by reaction with sodium hydride and methyl iodide. Conversion of the phenolic group to an amino group, which can subsequently be alkylated by conventional means to produce a secondary amine if desired, can be effected by the Bucherer reaction using sodium bisulfite and ammonia. The phenol group may be esterified, for example, with an acid anhydride or acid halide to produce an alkanoyloxy or aralkanoyloxy, R^ group. Production of compounds wherein R^ is sulfhydryl or an alkyl-, aryl-, aralkyl-thi group can be effected by first converting the phenolic hydroxyl group obtained by demethylation of galanthamine to a thiol group. This can be effected, for example, by the Newman-Kwart rearrangement described, for example, in S. Patai ed "The Chemistry of the Thiol Group" Part 1 John Wiley & Sons, New York 1974 pages 201-206. This rearrangement is effected in three steps: (1) conversion of the hydroxyl group to the O-aryl dialkylthioσarba ate by treatment with dialkylthioσarbonyl chloride; (2) pyrolysis of the O-aryl dialkylthioσarbamate to the S-aryl dialkylthiocarbamate; and (3) hydrolysis of this product to the aryl mercaptan. The first stage reaction with dimethylthiocarbamyl chloride may be effected by dissolving the phenol obtained by demethylation of galanthamine in aqueous potassium hydroxide at 10°C or below and then reacting this with dimethyl¬ thiocarbamyl chloride in tetrahydrofuran at temperatures not exceeding 12°C. The solution is made alkaline and the O-aryl dimethylthiocarbamate is separated. This compound is pyrolyzed at 270-275°C for about 45 minutes in a salt bath, and treated with potassium hydroxide in ethylene glycol. The reaction is cooled, the product extracted and worked up. The thiol group can be converted to an alkali metal salt if desired by reaction with sodium or potassium hydroxide or sodium hydride. This salt may be alkylated to produce compounds wherein R j _ is alkylthio, arylthio, aralkylthio or alkarylthio by any one of a wide variety of alkylating agents, for example, as described by P.D. Boyer in J. A er. Chem. Soc. 76 4331 (1954) . The production of the thiol group also provides a convenient route for the production of compounds wherein ^_ is hydrogen. The thiol may be desulfurized, for example, by refluxing with Raney nickel in absolute alcohol or dioxane, for example, as described by R.L. Augustine "Catalytic Hydrogenation" Marcel Dekker Inc., New York 1965 pp 131-133. Production of a galanthamine analogue where R 2 is an alkanoyloxy or benzoyl group can be obtained by a simple esterification reaction. Compounds wherein R2 is alkyloxy, aryloxy, aralkyloxy or alkaryloxy may be formed by forming a salt of the alcohol by reaction with sodium and thereafter reacting the salt with alkyl or other halide as described above for alkylating a phenol salt to produce R^ as other than methyl. Similarly, reaction of the hydroxy group with an aryl or alkyl isocyanate will produce compounds wherein R 2 is a monoaryl or monoalkyl carbamate In other transformations of the R 2 group, the first step in modification will normally be conversion of the allylic alcohol into an allylic bromide. This may be effected by reaction with a slight excess of carbon tetrachlorida and triphenylphosphine in a solvent such as methylenβ chloride at reduced temperature, for example, around 0°C. The bromide may then be reacted with magnesium in a Grignard reaction and the Grignard reagent obtained reacted with water to produce a compound wherein R 2 is hydrogen. Alternatively, reaction of the allylic bromide with lithium aluminum hydride may achieve the same product. The allyl ' bromide may also be used as an intermediate for the introduction of other groups into the C ring. For example, the bromide will react with nucleophiles such as sodium or potassium hydrosulfide to replace the bromo group by a hydrosulfuryl group or with sodium cyanide to introduce a cyano group. The hydrosulfuryl group may be converted into a salt and alkylated in the same ways as can a hydrosulfuryl group in the A ring. The allylic hydroxyl group may also be converted into a keto group. This can be accomplished, for example, by reaction with Jones reagent (H 2 Cr0 4 , H 2 S0 4 water and acetone). Proceeding via the keto group may also be an alternative route to production of compounds wherein R 2 is hydrogen. For example, the keto compound may be reacted with ethane dithiol and boron trifluoride etheratβ and the 1,3-dithiolane produced then desulfύrized by reaction with Raney nickel. The ketone intermediate may also be used as a source for compounds wherein R 2 is amino, such compounds being obtained by reductive amination of the keto group with ammonia and hydrogen in the presence of a nickel catalyst. Further analogues that can be obtained by use of the ketone as an intermediate are those wherein Rg is other than hydrogen. These can be obtained by reaction of the ketone with a Grignard reagent. The ketone may also be used as an intermediate for the production of compounds wherein R 7 is hydroxy methyl by first effecting an o . -bro ination of the ketona and then converting this to hydroxy methyl. When R2 and Rg jointly form a semi carbazone this can be formed from the ketone by reaction with semi carbazida. In order to produce compounds wherein R3 is other than methyl, galanthamine is first demethylated to produce a compound wherein R3 is hydrogen. Demethylation may be effected by reaction with a chloroformate such as methyl chloroformate or phenyl chloroformate to produce a carbamate which may then be cleaved with hydrazine, or by reaction with β,β,β-triσhloromethyl chloroformate followed by reaction with zinc and acetic acid. The resulting amine may then be alkylated with other alkyl groups, branched or unbranσhed, alkylphenyl group or alkylheterocyσlic groups. This reaction may be carried out by converting -NH to the corresponding sodium or potassium salt (NaH, KH) and treating the salt with the corresponding halide, preferably iodides, but bromides and chlorides might be used. All the halides used are commercially available. The reaction conditions may be modified for less reactive halides such as chlorides or aryl or heterocyclic halides which may also be less reactive. For instance, a special method is needed for N-phenylation as described by D.H.R. Barton, J.P. Finet and J. Khamsi, Tetrahedron Letters 28., 887 (1987) . It is also possible to change the degree of saturation of the "core" structure of galanthamine. For example, if one forms an allylic bromide in the C-ring as described above, this bromide may be subject to catalytic hydrogenation in the presence of palladium, for example, palladium on carbon in ethanol at room temperature and atmospheric pressure to remove not only the bromine atom, but also to saturate the unsaturated bond in the C ring. The C-ring may be oxidized to produce a further unsaturated bond by oxidation, for example, by heating with nickel, platinum or palladium at 300-350°C or possibly under milder conditions if acceptors such as maleic acid, cyσlohexane or benzene are present. The oxygen of the B ring of galanthamine may be replaced by N-R' by reaction with ammonia or an amine in the gas phase at high temperatures in the presence of activated aluminum oxide or aluminum silicate as described, for example, in Yu. K. Yur'ev and E.G. Vendel'shtein, Zh. Obshch. Khim. , 21, 259 (1951); CA. 45, 7564, (1951); Ibid. 23., 2053 (1953); C . 49., 3120 (1955) ; H. Sugisawa and K. Aso, Tohoku J. Agr. Res., 10, 137 (1959); CA. 54, 11015 (1960). R 6 substituents may be introduced into the D-ring for example by Procedure No. 4 hereinafter. Conversion of 3 to hydroxy methyl may be effected by photolyzing in the presence of cyanogen chloride to introduce a cyano group. This may be reduced using a Ranez nickel catalyst to produce an aldehyde group that can itself be reduced to hydroxy methyl. Similar conversions can be affected using lycoramina as starting material to produce compounds wherein the C ring is saturated. In addition to modifying galanthamine, compounds according to the present invention may also be produced by cyσlizing an amide of the formula: R lf R 3 and R 4 groups may be selected as desired in the starting material employed. Cyclization is effected by electrochemical oxidation of the type described in U.S. Patent 4,290,862 for preparing narwedine-type enones. The linear precursor in an appropriate solvent with a conductive salt and 2% HBF 4 or KC10 4 or K 2 C0 3 is added to the anode compartment of an electrolytic cell. The cathode compartment and the electrolytic bridge of the reference electrode contains the same anodic solvent and the same percentage of conductive salt. The working electrode is platinum. Oxidation is carried out at 1.3 volts at low temperatures (below 0°C) . This procedures after workup of the product affords cyclization products. The compounds of the present invention may be used for the treatment of Alzheimer's disease either in free base form or as the acid addition salts. The compounds can be administered in any convenient chemical or physical form. For example, they nay be administered as pharmaceutically acceptable salts, as long as these do not quatemisβ the D-ring nitrogen atom. Useful salts include the hydrobromide and hydrochloride. The compounds or the pharmaceutically-aσceptance acid addition salts may be administered to a patient suffering from Alzheimer's disease orally or by subcutaneous or intravenous or injection. Sustained release delivery mechanisms are particularly useful for administration of the compounds of the present invention, for example, intracerebroventricularly by means of an implanted reservoir by use of sustained release capsules or by means of a trans dermal patch. It may be necessary to begin at lower doses than are ultimately effective. Certain of the compounds may be only sparingly soluble in water at room temperature and so injeσtabla compositions are normally in the form of an aqueous suspension. If necessary, pharmaceutically-acceptable suspension aids may be employed. Typically, such a suspension will be employed at a concentration of 1-50 mg/ml more commonly 5-40 mg/ml, for example, 5-30 mg/ml or 10-40 mg/ml, typically 20-30 mg ml of the compound of the present invention. Typical dosage rates when administering compounds of the invention will depend upon the exact nature and condition of the patient. For example, typical dosage rates for administration by injection are in the range 5-1,000 mg per day depending upon the patient. In some cases, even lower dosages such as 0.5 or 1 mg per day may be helpful. For example, divided doses in the range 0.5-5 g/kg body weight per day may prove useful. Typically, one might administer a dosage of 50-300 mg per day to a patient of a body weight of 40-100 kg, although in appropriate cases such dosages may prove useful for patients having a body weight outside thia range. In other cases, dosages as low as 10 mg and as high as 500 mg may be appropriate for persons in this body weight range. The compounds of the invention may also be administered orally, for example, as an aqueous suspension or a solution in aqueous ethanol or as a solid such as a tablet or capsule. Suspensions or solutions for oral administration are typically of about the same concentration as those used for injections. However, it may be desirable when administering the drug orally to use a higher dosage rate than when administering it by injection. For example, dosages up to 2000 mg per day may be used, such as dosages in the range 100-600 mg per day. In preparing such tablets or capsules, standard tablet or capsule-making techniques may be employed. The dosage rate of the compound of the invention or its pharmaceutically-acceptable salt will normally be in the same range as for oral administration of a liquid. If desired, a pharmaσβutically-acceptable carrier such as starch or lactose may be used in preparing tablets. Capsules may be prepared using soft gelatine as the encapsulating agent. If desired, such capsules may be in the form of sustained release capsules wherein the main capsule contains miσrocapsules of active compound which release the contents over a period of several hours thereby maintaining a constant level of active compound in the patient's blood stream. The following test provides a good animal model for Alzheimer's disease in humans: A selective lesion is placed in a subcortical nucleus (nucleus basalis of Meynert) with a resultant cortical cholinergic deficiency, similar in magnitude to that seen in early to moderate stage Alzheimer's disease. Numerous behavioral deficits, including the inability to learn and retain new information, characterizes this lesion. Drugs that can normalize these abnormalities would have a reasonable expectation of efficacy in Alzheimer's disease. Haroutunian, V, Kanof P, Davis, KL: Pharmacological alleviations of cholinergic-lesion-induced memory defects in rats. Life Sciences 37:945-952, 1985. The following specific formulations may find use in treatment of Alzheimer's disease: Tablets or capsules containing 5, 10 and 25 mg hydrobromide of a compound according to the invention to be taken four times a day, or a sustained-release-preparation delivering an equivalent daily dose. Parenteral solution containing 5 mg/ml. Liquid formulation for oral administration available in 5mg/5ml and 25mg/5ml concentration. There have been reports that galanthamine can cause cardiac arrythmias. If such problems occur with the compounds of the present invention, it may be desirable to administer compounds of the invention in conjunction with another drug such as propanthelinbromide to control such arrythmias. As with other drugs that act on the central nervous system, minor side effects, such as nausea, may be noted. In this case, the compounds of the present invention will be administered in conjunction with agent for control of such side effects. A substantial proportion of patients suffering from Alzheimer's disease exhibit not only reduced levels of acetyl choline but also of norepinephrine in the brain. In such cases, the compounds of the present invention may advantageously be employed in conjunction with compounds such as clonidine desipramine, monoamine oxidase inhibitors, methamphetamine and methyl phenidate that stimulate the noradrenergic receptors in the brain. PROCEDURES ; 1. Conversion of oxygen to nitrogen in furanold ring. This transformation has been accomplished by several authors. Passage of furan and its homologs, or reduced furans with ammonia over alumina, at 400-450OC, affords the corresponding pyrroles. With primary, amines the N-substituted pyrrole is obtained. A typical procedure is as follows. The furan derivative is dissolved in liquid ammonia and. passed over an alumina catalyst (200 c.c. 4-6 mesh) which has been preheated to 400°C 1 Alternatively, a mixture of a furan derivative and ammonia in aqueous- alcoholic medium may be heated at temperature around 110 Q -15QOC. The reaction proceeds more readily under pressure and therefore can be carried out in an autoclave.2 1. CL. Wilson, /. Chem. Soc. 63. 1945. 2. R.C. Fuson, CL. Fleming, R. Johnson, . Am. Chem. e. 60, 1994 (1938). 2. Introduction of -CH2OH at position 16. Position 16 is next to the furan ring. This position is equivalent to' the α-position of an ether and therefore prone to radical attack by reagents such as oxygen, peroxides, and photochemical reactions. Irradiation of cyclic ethers in the presence of cyanogen chloride is known to produce α-cyano ethers in good yields. 1 Therefore, a similar reaction on galanthamine should introduce a cyano group in this position. The cyano group is known to be converted to an aldehyde with Raney Nickel and formic acid.^ The aldehyde may in turn be reduced with any reducing agents to the hydroxymethyl group.3 A typical procedure is as follows. Tne photolysis is carried out using a mercury lamp S-81 in a water cooled, unfiltered quartz immersion well. A solution of equimolar amounts of galanthamine and cyanogen chloride, in a spectral grade solvent, is irradiated with stirring, in a nitrogen atmosphere, and in a quartz cell. The reaction is irradiated for 2h in the presence of sodium bicarbonate. The sodium bicarbonate is essential to absorb the hydrogen chloride. Lower yields are obtained in the absence of the reagent. The fmal mixture is filtered, concentrated, washed with appropriate reagents and dried. Removal of solvent affords the product. . ; • ' 1 • The cyano derivative obtained is dissolved in 75% (v/v) of aqueous formic acid and treated with a 50:50 Ni-Al alloy (Raney type). The mixture is heated for 3h at 95 C, diluted with absolute ethanol-ethyl acetate and filtered through Celite. The filtrate is concentrated, washed with appropriated reagents and dried. Removal of solvent affords the product. The aldehyde derivative is dissolved in isopropanol and added to a solution of sodium hydroxide and sodium borohydride, dropwise, at such rate that the reaction refluxes gently. After standing overnight, the reaction is worked up as usual. 1. E. Muller, H. Huber, Chem. Ber. 96, 2319 (1963). 2. T. van Es, B. Stakun, . Chem. Soc. 5775 (1965). 3. S.R. Sandier, W. Karo, Organic Functional Group Preparations", Vol 12, 1968. Academic Press, pp. 89-90. . onvers on o - e a pos on o o er su s uent^. The reaction will require demethylation of the methoxy group. Although demethylation of aromatic alkoxy group is considered a standard reaction, this operation may be tricky in polysubstituted systems. A successful approach is the reaction of boron tribromide at OOC* The phenol obtained may be converted to a bromide by standard procedure.* Generation of a lithium anion at this positions allows a variety of reactions such as treatment with alkyl halides to give " alkyl groups, carbon dioxide to afford acids or aldehydes and ketones to give alcohols. A typical procedure follows. A 1M solution of boron tribromide is added dropwise to a solution of galanthamine in dry methylene chloride at OOC, under nitrogen. After stirring at OOC for 3h, the excess reagent and boron complexes are hydrolyzed by water. The product is obtained by extraction of the aqueous layer with ether. Removal of the solvent affords the compound. The phenol derivative is mixed thoroughly with phosphorus pentabromide and heated at 70-80OC, then at 120OC Hydrolysis with ice and water affords the crude bromo compound which may be recrystallized from an appropriate solvent. A solution of n-butyl lithium was added dropwise, at -780C, under argon, to the bromo derivative dissolved in tetrahydrofuran and hexamethyl phosphoramide to generate the intermediate anion. To this anion, one may add any alkyl halide to form an derivative. Alternatively, the solution could be poured over dry ice to afford the corresponding carboxylic acid, or to an aldehyde or ketone to form the corresponding alcohol derivative. Treatment of this anion with ethyl chloracetate would give the corresponding ethyl carboxymethyl derivative. The above methodology is general to introduce various groups in place of the methoxy group in the aromatic ring (position 13). 1. S-Y Han, J.T. Gordon, K. Bhat, M.B. Dratman, M.M. Joullie', Int. J. Peptide Protein Res. 30, 1987, 652. 2. CE. Kaslow and M.M. Marsh, . Org. Chem. 12, 456 (1947). 3. J. Chiarello and M.M. Joullie', Tetrahedron, 44, 41 (1988). 4. Conversions in the D ring Removal of the methyl group in the D ring of galanthamine can be accomplished by the classical von Braun reaction.1 The reaction may be manipulated to give either demethylation to a secondary amine or to open the ring. Either of these procedures will give rise to new analogs. Ring opening would afford two chains, one at position 10, possibly a bromoethyl groups and one at position 5, a N-methyl propylamine. These could be used to study the effect of disrupting ring D. However, demethylation would serve to functionality in ring D via the formation of an imine. A typical procedure for introduction of substituents in ring D follows. Treatment of N-demethylated galanthamine with tert-butyl hypochlorite at 0°C will afford the N-chloro derivative. This sensitive compound is not isolated but immediately dehalogenated with either sodium methoxide or diazabicycloundecene to afford the highly unstable pyrroline. This intermediate can be treated with nucleophiles3 or with benzoic and, tørNbutylisonitrile as described in reference 2. 1. H.A. Hagerman, Org. Reactions, VII, Chap 4 (1953). 2. R.F. Nutt, M.M. Joullie', J. Am. Chem. Soc, 104, 5852 (1982). 3. J. Hausler, U. Schmidt, Liebigs Ann. Chem. 1881 (1979). The production of compounds of the present invention is illustrated by the following Examples: EXAMPLE 1 i To a solution of Galanthamine (1, 0.7g, 0.2439 mmoles) in dry methylene chloride (4 ml) , pyridinium chlorochromate (0.1577g, 0.7317 mmoles) was added and stirred at room temperature for 8 hours. The reaction mixture was diluted with methanol and filtered. Removal of solvent followed by purification on a silica gel column using acetone, methanol:acetone (10:90) as eluants afforded the desired product. (0.06g, 86% yield). mp. 184-186°C EXAMPLE 2 To a solution of JL (0.07g, 0.2439 mmoles) in methylene chloride, acetic anhydride (0.03 ml, 0.317 mmoles) and dimethylaminopyridine (0.0536g, 0.439 mmoles) ware added at 0°C in an ice bath. The reaction mixture was stirred at )°C for 10 minutes and room temperature for 60 minutes. Solvents were removed on a rotary evaporator and the residue was diluted with ethyl acetate, washed with water, 10% Na C0 3 , brine and dried (N 2 Sθ 4 ) concentration of the solvent and purification by silica gel chromatography using Acetone, MeOH:Acetone (1:10) as eluants afforded 0.0773g of product (96% yield) . mp. 126-128°C EXAMPLE 3 Phenylisocyante (0.033 ml, 0.2926 mmoles) was added to a stirred solution of 1 (0.07 g, 0.2439 mmoles) in the THF (5 ml) at room temperature, and then stirred for 30 hours at the same condition. The reaction mixture was concentrated, purified by silica gel column chromatography using Acetone, MeOH:Acetone (10:90) to give 0.0982g (99% yield) of product, mp 79-81°C EXAMPLE 4 Ttfp 1-Naphthyl isocyante (0.042 ml, 0.2925 mmoles) was added to a stirred solution of 1 (0.07g, 0.2439 mmoles) in THF (5 ml) at room temperature. The reaction mixture was stirred for 24 hours at room temperature, and then concentrated. The crude reaction mixture was purified by silica gel column chromatography using acetone, methanol:acetone (10:90) as eluants to afford O.llg of product (99%). mp. 198-200°C EXAMPLE 5 To a solution of 1 (O.lg, 0.3484 mmoles) in methanol, 20% palladium on carbon (0.02g) was added and hydrogen atmosphere was applied. The reaction mixture was stirred for 10 hours at room temperature. The catalyst was filtered off through celite, washed thoroughly with methanol. The solution was concentrated, and the crude material was purified on a silica gel column using acetone: ethanol (90:10, 80:20) to afford 0.0938g (93% yield) of the product, mp 110-112°C Anticholinesterase activity of the compounds of the above examples was assayed by an assay for inhibition of acetylσholinesterase following the procedure of G. Ellman, Biological Pharmacology, 1961, Vol. 7, pp 88-95. Acetylthioσholine serves as substrate since it acts like acetylcholine. Acetylcholinesterase cleaves it to thiocholine and acetate which react with dithiobisnitrobenzoate to form a yellow color which is measured photometrically. The assay results are shown in the following table, which also includes an assay of the activity of galanthamine. TABLE COMPOUND PERCENT INHIBITION OF ACETYLCHOLINESTERASE Galanthamine 95% Product of Example 1 10% Product of Example 2 37% Product of Example 3 37% Product of Example 4 60% Product of Example 5 30%

Claims: C L A I M S 1. A method of treating Alzheimer's disease and related dementias which comprises administering to a patient suffering from such a disease a therapeutically effective amount of a compound of the formula I wherein the broken line represents an optionally present double bond in one or the two of the portions shown, R^ and R 2 are each selected independently from the group consisting of hydrogen, hydroxyl, amino or alkylamino, cyano, sulfhydryl, alkoxy of 1-6 carbon atoms, alkylthio, aryloxy, arylthio, R 5 - substituted aryloxy, R 5 -substituted arylthio, aralkoxy, an aliphatic or aryl carbamyl group wherein the aliphatic or aryl moiety may be R5 substituted or unsubstituted, aralkylthio, R 5 -substituted aralkoxy, R 5 -substituted aralkylthio, aryloxymethyl, Rs-substituted aryloxymethyl, alkanoyloxy, hydroxy-substituted alkanoyloxy, benzoyloxy, R5~substituted benzoyloxy, aryloxy earbonyl and R5-substituted aryloxy earbonyl, R^_ may also by alkyl of up to 14 carbon atoms, or hydroxy methyl, R 2 may also be carboxymethyl provided that at least one of ] _ and R 2 is hydroxy, amino or alkylamino unless Rγ or R3 is hydroxymethyl, 3 is hydrogen, straight or branched chain alkyl, of 1-6 carbon atoms, cycloalkyl methyl, phenyl, 5 substituted phenyl, alkylphenyl, Rs-substituted alkylphenyl, heterocyclyl selected from <r \ - or β-furyl, c<_ or β-thienyl or thenyl, pyridyl, pyrazinyl and pyri idyl, alkyl heterocyclyl or R'- substituted heterocyclyl, where R' is alkyl or alkoxy each 4 is independently selected from hydrogen, hydroxyl, sulfhydryl, alkyl, aryl, aralkyl, alkoxy, mercaptoalkyl, aryloxy, thioaryloxy, alkarloxy, merσaptoalkaryl, nitro, amino, N-alkylamino, N-arylamino, N- alkarylamino, fluoro, chloro, bromo iodo and trifluoromethyl, R 5 is selected from the same groups as R 4 , R 6 is hydrogen, halo, trifluoromethyl or alkyl of 1 to 4 carbon atoms, R 7 is selected from the same groups as 4 or may be hydroxy alkyl of 1-2 carbon atoms, R3 is hydrogen or hydroxymethyl, Rg is hydrogen or alkyl of 1 to 6 carbon atoms, or when R 2 is hydroxyl Rg may be a moiety of formula I wherein R 9 is hydrogen and R 2 is a linking bond; or R 2 and Rg may jointly form a semi carbazone, X is oxygen or NR 5 , Y is nitrogen or phosphorus and methylenedioxy derivatives thereof with the proviso that when X is 0, R 3 is not methyl when R is methoxy, R 2 is hydroxy, and all R 4 are hydrogen or a pharmaceutically- acceptable acid addition salt thereof. 2. A method according to claim 1 wherein the compounds used is one wherein R^ and R 2 are each selected from wherein R is alkyl 1-6 carbon atoms or phenyl or R 5 - substituted phenyl or benzyl or R 5 -substituted benzyl, wherein R 10 s hydrogen, alkyl or alkoxy, R 3 is -H, or branched on linear alkyl or wherein n is 3, wherein R 10 is as defined above where Z is 0, S , or NH or X is oxxygen-andxY is nitrogen. 3. A method according to claim 1 wherein said compound is of the formula: wherein R 1 is as defined in claim 1, preferably hydroxy, lower alkoxy, aryloxy, R 5 substituent aryloxy, benzyloxy or R 5 substituted benzyloxy, amino, alkyl amino or an alkyl or aryl carbamyl group. 4. A method according to claim 3, wherein said compound is selected from O-demethyl, N-demethyl galanthamine; O-ethyl, O-demethyl, N-demethyl galanthamine; 0-phenyl, O-demethyl, N- de ethyl galanthamine; and O-benzyl, O-demethyl galanthamine. 5. A method according to claim 1 wherein said compound is of the formula: r^ wherein R 2 is hydroxy, lower alkoxy, arloxy, R 5 substituted arloxy benzyloxy or R 5 substituted benzyloxy or an alkyl or aryl carbamyl group and R 3 is hydrogen or alkyl of 1-6 carbon atoms such as methyl or ethyl, methyl cyclopropyl or benzyl or R 5 -substituted benzyl. 6. A method according to claim 5, wherein said compound is selected from O-demethyl galanthamine; O-demethyl galanthamine; O-methyl ether; O-demethyl galanthamine; O-ethyl ether; O-demethyl galanthamine, O-benzyl ether; O-demethyl galanthamine, phenyl and O-demethyl N-demethyl galanthamine, -naphthyl carbamates; O-demethyl galanthamine dimethyl carbamate and O-dimethyl galanthamine diethyl carbamate wherein the carbamyl group is bonded to the oxygen of the cyclohexene ring, and the corresponding N-demethyl and N- demethyl N-ethyl and N-demethyl N-cyclopropyl methyl and N- demethyl N-benzyl compounds. 7. A method according to claim 1, wherein said compound is of the formula: wherein R 1 , R 2 and R 3 are as defined in claim 1. 8. A method according to claim 7, wherein the compound employed is one wherein R 1 is typically being hydroxy, lower alkoxy, benzyloxy or R 5 substituted benzyloxy, amino alkylamino or alkyl or aryl carbamyl, R 2 is hydroxy, lower alkoxy, arloxy, benzyloxy or an alkyl or aryl carbamyl group but is preferably hydroxy and R 3 is hydrogen, methyl, ethyl, cyclopropyl methyl or benzyl. 9. A method according to claim 8, wherein said compound is selected from O-demethyl lycoramine; N-demethyl, O-demethyl lycoramine; N-demethyl N- ethyl lycoramine; N-demethyl N- cyclopropylmethyl lycoramine; N-demethyl N-benzyl lycoramine; O-demethyl lycoramine ethyl ether; deoxy O-demethyl lycoramine; O-deoxy demethyl lycoramine, benzyl ether and dimethyl and phenyl carbamyl analogs of such compounds. 10. A method according to claim 1, wherein said compound is of the formula: wherein R 3 is selected from hydrogen, lower alkyl, cycloalkyl methyl or benzyl. 11. A method according to any one of the preceding claims, wherein the administration is parenteral at a daily dosage of 0.5-1,000 mg of a compound of formula 1 as claimed in claim 1 or a pharmaceutically-acceptable acid addition salt thereof. 12. A method according to any one of the preceding claims, wherein said dosage rate is 50-300 mg per day. 13. A method according to any one of preceding claims 1- 10, wherein said administration is oral and is in the range 10-2000 mg per day. 14. A method according to claim 13, wherein said dosage rate of 100-600 mg per day. 15. A method according to any one of claims 1-10, wherein a compound according to any one of claims 1-10 is administered at a dosage rate of 0.1 to 4 mg/kg body weight of a patient, parenterally. 16. A method according to any one of claims 1-10, wherein a compound according to any one of claims 1-10 is administered intracerebroventriσularly via an implanted reservoir at a dosage rate of 0.01 to 5.0 mg/kg day. 17. A method according to any one of claims 1-10, wherein a compound according to any one of claims 1-10 is administered in a sustained release formulation. 18. A wherein the broken line represents an optionally present double bond in one of the two portions shown, R^ and R 2 are each selected independently from the group consisting of hydrogen, hydroxyl, amino or alkylamino, cyano, sulfhydryl, alkoxy preferably of 1-6 carbon atoms, alkylthio, aryloxy, arylthio, R 5 -substituted aryloxy, Rs-substituted arylthio, aralkoxy, an aliphatic or aryl carbamyl group wherein the aliphatic or aryl moiety may be R 5 substituted or unsubstituted, aralkylthio, R 5 -substituted aralkoxy, R 5 - substituted aralkylthio, aryloxymethyl, R 5 substituted aryloxymethyl, alkanoyloxy, hydroxy-substituted alkanoyloxy, benzoyloxy, R 5 -substituted benzoyloxy, aryloxy earbonyl and R5~substituted aryloxy earbonyl, R^ may also by alkyl of up to 14 carbon atoms, or hydroxy methyl, R 2 may also be keto; R 2 may also be carboxymethyl provided that at least one of ^_ and R is hydroxy amino or alkylamino unless R7 or R3 is hydroxymethyl, R 3 is hydrogen, straight or branched chain alkyl. preferably of 1-6 carbon atoms, cycloalkyl methyl, alkylphenyl, Rs-substituted alkylphenyl, heterocyclyl such as σ{- or β-furyl, - or β-thienyl or thenyl, pyridyl, pyrazinyl or pyrimidyl groups, alkyl heterocyclyl and R'-substituted heterocyclyl, where R^ is alkyl or alkoxy each R 4 is independently selected from hydrogen, hydroxyl, sulfhydryl, alkyl, aryl, aralkyl, alkoxy, thioalkoxy, aryloxy, thioaryloxy, alkarloxy, thioalkaryloxy, nitro, amino, N-alkylamino, N-arylamino, N-alkarylamino, fluoro, chloro, bromo iodo and trifluoromethyl, and R 5 is selected from the same groups as R4, Rg is hydrogen, halo, trifluoromethyl or alkyl of 1 to 4 carbon atoms, R 7 is selected from the same groups as R 4 or may be hydroxy or merσapto alkyl of 1-2 carbon atoms, R 8 is hydrogen or hydroxymethyl, Rg is hydrogen or alkyl of 1 to 6 carbon atoms, or when R 2 is hydroxyl Rg may be a moiety of formula I wherein Rg is hydrogen and R is a linking bond; or R and Rg may jointly form a semi carbazone, X is nitrogen, Y is nitrogen or phosphorus and oxidized and reduced and methylenedioxy derivatives thereof with the proviso that when X is O, R 3 is not methyl when Ri is methoxy, R 2 is hydroxy, and all R 4 are hydrogen and pharmaceutically-acceptable acid addition salts thereof. wherein the broken line represents an optionally present double bond in one of the two portions shown, R j _ and R 2 a a each selected independently from the group consisting of hydrogen, hydroxyl, amino or alkylamino, cyano, sulfhydryl, alkoxy preferably of 1-6 carbon atoms, alkylthio, aryloxy, arylthio, R 5 -substituted aryloxy, Rs-substituted arylthio, aralkoxy, an aliphatic or aryl carbamyl group wherein the aliphatic or aryl moiety may be R5 substituted or unsubstituted, aralkylthio, R 5 -substituted aralkoxy, R 5 - substituted aralkylthio, aryloxymethyl, R 5 -substituted aryloxymethyl, alkanoyloxy, hydroxy-substituted alkanoyloxy, benzoyloxy, Rs-substituted benzoyloxy, aryloxy earbonyl and R5-substituted aryloxy earbonyl, ^ may also by alkyl of up to 14 carbon atoms, or hydroxy methyl, R 2 may also be keto; R 2 may also be carboxymethyl provided that at least one of R T and R 2 is hydroxy amino or alkylamino unless R 7 or R 8 is hydroxymethyl , R 3 is hydrogen, straight or branched chain alkyl, preferably of 1-6 carbon atoms, cycloalkyl methyl, alkylphenyl, R 5 -substituted alkylphenyl, heterocyclyl such as <? - or β-furyl, ( ^ or β-thienyl or thenyl, pyridyl, pyrazinyl or pyrimidyl groups, alkyl heterocyclyl and R'-substituted heterocyclyl, where ^ is alkyl or alkoxy each R4 is independently selected from hydrogen, hydroxyl, sulfhydryl, alkyl, aryl, aralkyl, alkoxy, thioalkoxy, aryloxy, thioaryloxy, alkaryloxy, thioalkaryloxy, nitro, amino, N-alkylamino, N-arylamino, N-alkarylamino, fluoro, chloro, bromo iodo and trifluoromethyl, and R5 is selected from the same groups as R 4 , Rg is hydrogen, halo, trifluoromethyl or alkyl of 1 to 4 carbon atoms, R 7 is selected from the same groups as R 4 or may be hydroxy or mercapto alkyl of 1-2 carbon atoms, R 8 is hydrogen or hydroxymethyl, Rg is hydrogen or alkyl of 1 to 6 carbon atoms, or when R 2 is hydroxyl Rg may be a moiety of formula I wherein Rα is hydrogen and R 2 is a linking bond; or R and Rg may jointly form a semi carbazona, X is oxygen, Y is nitrogen or phosphorus and oxidized and reduced and methylenedioxy derivatives and pharmaceutically-acceptable acid addition salts thereof with the proviso that when X is O, R 3 is not methyl when R^ is methoxy, R 2 is hydroxy, and all R 4 are hydrogen provided that when the 3-4 bond is saturated, R^ is not hydrogen when R is methoxy or hydroxy, R 4 is hydrogen, R 3 is methyl and R7 is hydrogen or ethoxy, and R^ is not acetoxy when R 2 is hydroxy, R 3 is methyl, R is hydrogen and R7 is hydrogen and when R is hydroxy, R 3 is not hydrogen or benzyl when R± is methoxy and all of R 4 and R 7 are hydrogen, and further provided that the compound is not leucotamine, 0- methyl leucotamine, O-methyl leucotamine acetate, sanguinine, lycoramine, O-demethyl lycoramine, childanthine, habranthine, N-formyl galanthamine, acetyl dihydrogalanthamine or N,0- diacetyl N-demethylgalanthamine, deoxydemethyl lycoramine, lycoramine acetate, deoxylycoramine or deoxydemethyl lycoramine carbamate. 20. A medicine for treatment of Alzheimer's disease and related dementias comprising a compound as specified in claim 1. 21. A medicine according to claim 20 in the form of a sustained release product. 22. Use of a compound as specified in claim 1 for the production of a pharmaceutically composition for treatment of Alzheimer's disease or related dementias.

Inventors: DAVIS BONNIE, JOULLIE MADELEINE, DAVIS, BONNIE, JOULLIE, MADELEINE
Applicants: BONNIE DAVIS, DAVIS, BONNIE
Application year: 1988
Main classification: A61K31
IPC codes: A61K31, A61P25, C07D487, C07D491, C07F9