Substituted-4-amino-3-pyridinols, a process for their preparation and their use as medicaments

Abstract: The present invention relates to compounds of the formula I where R₁ is hydrogen or loweralkyl; R₂ is hydrogen, loweralkyl, cycloalkyl, arylloweralkyl,loweralkylcarbonyl or loweralkoxycarbonyl; or alternatively the group as a whole is wherein R₄ is loweralkyl and R₅ is loweralkyl, cycloalkyl or arylloweralkyl; and R₃ is hydrogen, wherein R₆ is hydrogen, loweralkyl or phenyl, and R₇ is hydrogen or loweralkyl, with the proviso that R₁, R₂ and R₃ may not all be hydrogen, which compounds are useful for alleviating memory dysfunctions characterized by a cholinergic deficit. The invention relates further to a process for the preparation of the compounds of the invention.

Description: The present invention relates to substituted 4-amino-3-pyridinols, a process for their preparation and their use as medicaments. Nouv. J. Chim. (1979), 3 , 115 discloses the compound 3-hydroxy-4-acetamidopyridine. US-A-4 734 275 discloses 4-aminopyrid-3-yl urea derivatives which may be useful in the treatment of Alzheimer's disease. Curr. Res. Alzheimer Ther. (1988), 337 discloses 4-aminopyridine derivatives substituted in position 3 by various groups which may he useful in the treatment of Alzheimer's disease. The present invention provides compounds of the formula I where R₁ is (C₁-C₆)alkyl and R₂ is (C₁-C₆)alkyl, cyclo(C₃-C₇)alkyl or aryl(C₁-C₆)alkyl; wherein the term aryl is a phenyl group substituted with 0, 1 or 2 substitutents which are each independently (C₁-C₆)alkyl, (C₁-C₆)alkoxy, halogen or trifluoromethyl; or alternatively the group as a whole is and R₃ is hydrogen, wherein R₆ is hydrogen, (C₁-C₆)alkyl or phenyl, and R₇ is hydrogen or (C₁-C₆)alkyl, or a pharmaceutically acceptable acid addition salt thereof. Preferably, in formula (I) R₁ and R₂ or the group as a whole is as defined above and R₃ is hydrogen, where R₆ is (C₁-C₆)alkyl or phenyl and R₇ is hydrogen or (C₁-C₆)alkyl. Even more preferably, in formula (I) R₁ and R₂ are independently (C₁-C₆)alkyl or the group as a whole is R₃ is hydrogen or where R₆ is (C₁-C₆)alkyl and R₇ is hydrogen or (C₁-C₆)alkyl. Most preferably, in formula (I) R₁ and R₂ are independently (C₁-C₆)alkyl and R₃ is where R₆ is hydrogen or (C₁-C₆)alkyl and R₇ is (C₁-C₆)alkyl. Unless otherwise stated or indicated, the following definitions shall apply throughout the specification and the appended claims. The term (C₁-C₆)alkyl shall mean a straight or branched alkyl group having from 1 to 6 carbon atoms. Examples of said alkyl include methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl and straight- and branched-chain pentyl and hexyl. The term cyclo(C₃-C₇)alkyl shall mean a cycloalkyl group of 3 to 7 carbon atoms. The term halogen shall mean fluorine, chlorine, bromine or iodine. Throughout the specification and the appended claims, a given chemical formula or name shall encompass all stereo and tautomeric isomers where such isomers exist. The compounds of this invention are prepared by utilizing one or more of the synthetic steps described below. Throughout the description of the synthetic steps, the notations R₁ through R₇ shall have the respective meanings given above unless otherwise stated or indicated. STEP A 4-Amino-3-pyridinol is allowed to react with an acetal of Formula IIa or IIb where represents to afford a compound of Formula IIIa or IIIb, respectively. This reaction is typically conducted at a temperature of 25 to 100°C. Optionally, a suitable third chemical may be added to the reaction mixture as a solvent such as toluene. STEP B Alternatively to the above, a compound of Formula IIIc obtained from STEP A is allowed to react with an amine of Formula IVa or IVb to afford a compound of Formula IIIa or IIIb, respectively. This reaction is typically conducted in a suitable solvent such as toluene at a temperature of 100 to 150°C. STEP C Compound IIIa or IIIb is allowed to react with an isocyanate of the formula O=C=N-R₇ in a routine manner known to the art to afford a compound of Formula Va or Vb, respectively. STEP D Compound IIIa or IIIb is allowed to react with a carbonyl chloride compound of Formula VIa (where R₆≠H) in a routine manner known to the art to afford a compound of Formula VIIa or VIIb, respectively. STEP E Compound IIIa or IIIb is allowed to react with a carbonyl chloride compound of Formula VIb where in a routine manner known to the art to afford a compound of Formula IXa or IXb, respectively. STEP F (For Reference Purposes) As an alternative to the foregoing steps, a compound of Formula XI, where R₆' and R₇' are each independently a loweralkyl of 2 to 6 carbon atoms, is allowed to react with secondary-butyllithium in the presence of tetramethylethylenediamine (TMEDA) to accomplish ortho-lithiation. The resultant lithio compound is first treated with tosyl azide and the resultant product is directly reduced with NaBH₄ under a phase transfer condition (tetra-n-butylammonium hydrogen sulfate is conveniently used for this purpose) to afford a compound of Formula Xc. The above reaction procedure is an application of the method described by Reed and Sniekus, Tetrahedron Letters, Volume 24, pp 3795-3798 (1983). STEP G As an alternative to STEP D, Compound Xc is allowed to react with Compound IIa or IIb in substantially the same manner as in STEP A to afford a compound of Formula VIIc or VIId, respectively. In other words, this represents a procedure where a methyleneamino group is introduced to the 4-position of the pyridine ring after a carbamate group has been introduced to the 3-position of the pyridine ring, which is in contrast to STEP D where a carbamate group is introduced after a methyleneamino group has been introduced. The compounds of Formula I of the present invention are useful for the treatment of various memory dysfunctions characterized by a decreased cholinergic function such as Alzheimer's disease. This utility is manifested by the ability of these compounds to inhibit the enzyme acetylcholinesterase and thereby increase acetylcholine levels in the brain. Cholinesterase Inhibition Assay Cholinesterases are found throughout the body both in the brain and in serum. However, only brain acetylcholinesterase (AChE) distribution is correlated with central cholinergic innervation. This same innervation is suggested to be weakened in Alzheimer patients. We have determined in vitro inhibition of acetylcholinesterase activity in rat striatum. In Vitro Inhibition of Acetylcholinesterase Activity in Rat Striatum Acetylcholinesterase (AChE), which is sometimes called true or specific cholinesterase, is found in nerve cells, skeletal muscle, smooth muscle, various glands and red blood cells. AChE may be distinguished from other cholinesterases by substrate and inhibitor specificities and by regional distribution. Its distribution in brain roughly correlates with cholinergic innervation and subfractionation shows the highest level in nerve terminals. It is generally accepted that the physiological role of AChE is the rapid hydrolysis and inactivation of acetylcholine. Inhibitors of AChE show marked cholinominetic effects in cholinergically-innervated effector organs and have been used therapeutically in the treatment of glaucoma, myasthenia gravis and paralytic ileus. However, recent studies have suggested that AChE inhibitors may also be beneficial in the treatment of Alzheimer's dementia. The method described below was used in this invention for assaying cholinesterase activity. This is a modification of the method of Ellman et al., Biochem. Pharmacol. 7 , 88 (1961). Procedure : A. Reagents - 1. 0.05 M Phosphate buffer, pH 7.2 (a) 6.85 g NaH₂PO₄·H₂O/100 ml distilled H₂O (b) 13.40 g Na₂HPO₄·7H₂O/100 ml distilled H₂O (c) add (a) to (b) until pH reaches 7.2 (d) Dilute 1:10 2. Substrate in buffer (a) 198 mg acetylthiocholine chloride (10 mM) (b) q.s. to 100 ml with 0.05 M phosphate buffer, pH 7.2 (reagent 1) 3. DTNB in buffer (a) 19.8 mg 5,5-dithiobisnitrobenzoic acid (DTNB) (0.5 mM) (b) q.s. to 100 ml with 0.05 M phosphate buffer, pH 7.2 (reagent 1) 4. A 2 mM stock solution of the test drug is made up in a suitable solvent and q.s. to volume with 0.5 mM DTNB (reagent 3). Drugs are serially diluted (1:10) such that the final concentration (in cuvette) is 10⁻⁴M and screened for activity. If active, IC₅₀ values are determined from the inhibitory activity of subsequent concentrations. B. Tissue Preparation - Male Wistar rats are decapitated, brains rapidly removed, corpora striata dissected free, weighed and homogenized in 19 volumes (approximately 7 mg protein/ml) of 0.05 M phosphate buffer, pH 7.2 using a Potter-Elvehjem homogenizer. A 25 microliter aliquot of the homogenate is added to 1.0 milliter vehicle or various concentrations of the test drug and preincubated for 10 minutes at 37°C. C. Assay - Enzyme activity is measured with the Beckman DU-50 spectrophotometer. This method can be used for IC₅₀ determinations and for measuring kinetic constants. Instrument Settings Kinetics Soft-Pac Module #598273 (10) Program #6 Kindata: Source - Vis Wavelength - 412 nm Sipper - none Cuvettes - 2 ml cuvettes using auto 6-sampler Blank - 1 for each substrate concentration Interval time - 15 seconds (15 or 30 seconds for Kinetics) Total time - 5 minutes (5 or 10 minutes for Kinetics) Plot-yes Span - autoscale Slope - increasing Results - yes (gives slope) Factor- 1 Reagents are added to the blank and sample cuvettes as follows: Blank: 0.8 ml Phosphate Buffer/DTNB 0.8 ml Buffer/Substrate Control: 0.8 ml Phosphate Buffer/DTNB/Enzyme 0.8 ml Phosphate Buffer/Substrate Drug: 0.8 ml Phosphate Buffer/DTNB/Drug/Enzyme 0.8 ml Phosphate Buffer/Substrate Blank values are determined for each run to control for non-enzymatic hydrolysis of substrate and these values are automatically subtracted by the kindata program available on Kinetics soft-pac module. This program also calculates the rate of absorbance change for each cuvette. For IC₅₀ Determinations: Substrate concentration is 10 mM diluted 1:2 in assay yielding final concentration of 5 mM. DTNB concentration is 0.5 mM yielding 0.25 mM final concentration. % Inhibition = slope control - slope drug slope control x 100 IC₅₀ values are calculated from log-probit analysis Results of this assay for some of the compounds of this invention and physostigmine (reference compound) are presented in Table 1. Compound Inhibitory Concentration (µM) Brain AChE 4-[[(Dimethylamino)methylene]amino]-3-pyridinyl ethylcarbamate 9.37 4-[[(Dimethylamino)methylene]amino]-3-pyridinyl N,N-dimethylcarbamate 83.0 4-[[(Dimethylamino)methylene]amino]-3-pyridinyl methylcarbamate 12.6 4-[[(1-Piperidinyl)methylene]amino]-3-pyridinyl N,N-dimethylcarbamate 47.1 4-[[(1-Pyrrolidinyl)methylene]amino]-3-pyridinyl N,N-dimethylcarbamate 9.38 Physostigmine 0.006 This utility is further demonstrated by the ability of these compounds to restore cholinergically deficient memory in the Dark Avoidance Assay described below. 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. Results of this assay for some of the compounds of this invention and those for tacrine and pilocarpine (reference compounds) are presented in Table 2. Compound Dose (mg/kg of body weight, s.c) % of Animals with Scopolamine Induced Memory Deficit Reversal 4-[[(Dimethylamino)methylene]amino]-3-pyridinyl N,N-diethylcarbamate 0.3 26.6% 4-[[(Dimethylamino)methylene]amino]-3-pyridinyl ethylcarbamate 0.1 20.0% 0.3 21.4% Tacrine 0.63 13% Pilocarpine 5.0 13% 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 capsule 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, chewing gum and the like. These preparations should contain at least 0.5% of active compounds, but may be varied depending upon the particular form and may conveniently be between 4% to about 70% 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 1.0 - 300 milligrams of active compound. The tablets, pills, capsules, troches and the like 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, Primogel (Trade Mark), cornstarch and the like; a lubricant such as magnesium stearate or Sterotex (Trade Mark); a glidant such as colloidal silicon dioxide; and a sweeting 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 purpose of parenteral therapeutic administration, the active compounds of the invention may be incorporated into a solution or suspension. These preparations should contain at least 0.1% of active compound, but may be varied between 0.5 and about 30% 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 inventions are prepared so that a parenteral dosage unit contains between 0.5 to 100 milligrams of active compound. The solutions or suspensions 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: 4-[[(dimethylamino)methylene]amino]-3-pyridinol; 4-[[(diethylamino)methylene]amino]-3-pyridinol; 4-[[(diisopropylamino)methylene]amino]-3-pyridinol; 4-[[(1-pyrrolidinyl)methylene]amino]-3-pyridinol; 4-[[(1-piperidinyl)methylene]amino]-3-pyridinol; 4-[[(hexahydro-1H-azepin-1-yl)methylene]amino]-3-pyridinol; 4-[[(4-morpholinyl)methylene]amino]-3-pyridinol; 4-[[(N-methyl-N-butylamino)methylene]amino]-3-pyridinol; 4-[[(N-cyclohexyl-N-methylamino)methylene]amino]-3-pyridinol; 4-[[(4-thiomorpholinyl)methylene]amino]-3-pyridinol; 4-[[(dimethylamino)methylene]amino]-3-pyridinyl methylcarbamate; 4-[[(dimethylamino)methylene]amino]-3-pyridinyl ethylcarbamate; 4-[[(dimethylamino)methylene]amino]-3-pyridinyl N,N-dimethylcarbamate; 4-[[(dimethylamino)methylene]amino]-3-pyridinyl phenylcarbamate; 4-[[(dimethylamino)methylene]amino]-3-pyridinyl piperidin-1-carboxylate; 4-[[(diethylamino)methylene]amino]-3-pyridinyl N,N-dimethyl carbamate; 4-[[(dipropylamino)methylene]amino]-3-pyridinyl N,N-dimethylcarbamate; 4-[[(1-pyrrolidinyl)methylene]amino]-3-pyridinyl N,N-dimethylcarbamate; 4-[[(1-piperidinyl)methylene]amino]-3-pyridinyl N,N-dimethylcarbamate; 4-[[(hexahydro-azepin-1-yl)methylene]amino]-3-pyridinyl N,N-dimethylcarbamate; 4-[[(4-morpholinyl)methylene]amino]-3-pyridinyl N,N-dimethylcarbamate; 4-[[(dimethylamino)methylene]amino]-3-pyridinyl N,N-diethylcarbamate; 4-[[(dihexylamino)methylene]amino]-3-pyridinyl N,N-dimethylcarbamate; 4-[[(diisopropylamino)methylene]amino]-3-pyridinyl N,N-dimethyl carbamate; 4-[[(N-methyl-N-butylamino)methylene]amino]-3-pyridinyl N,N-dimethyl carbamate; 4-[[(N-methyl-N-cyclohexylamino)methylene]amino]-3-pyridinyl N,N-dimethyl carbamate; 4-[[(benzylmethylamino)methylene]amino]-3-pyridinol; 4-[[(N-benzyl-N-methylamino)methylene]amino]-3-pyridinyl N,N-dimethylcarbamate; and 4-[[(thiomorpholin-4-yl)methylene]amino]-3-pyridinyl N,N-dimethylcarbamate. EXAMPLE 1 4-[[(Dimethylamino)methylene]amino]-3-pyridinol A solution prepared from of 4-amino-3-pyridinol (1.10 g) and 10 ml of N,N-dimethylformamide dimethyl acetal was refluxed for 30 minutes. At the end of this time, the reaction mixture was concentrated under reduced pressure and the residue was passed over a short column of Florisil (Trade Mark), eluting with 5% methanol/ethyl acetate. The eluate was concentrated and the residue and recrystallized from ethyl acetate/pentane to afford 0.91 g of analytically pure product, m.p. 121-123°. ANALYSIS: Calculated for C₈H₁₁N₃O: 58.17%C 6.70%H 25.44%N Found: 58.07%C 6.68%H 25.37%N EXAMPLE 2 4-[[(Diethylamino)methylene]amino]-3-pyridinol A mixture of 4-amino-3-pyridinol (3.90 g), N,N-diethylformamide dimethyl acetal (11.68 g) and toluene (20 mL) was heated under nitrogen for 2 hours. The solution was concentrated under reduced pressure. The resulting liquid was filtered through silica gel with 10% ethanol in tetrahydrofuran to give a solid. Recrystallization of the purified product from ethyl acetate/hexanes afforded 4.21 g of crystalline solid, m.p. 104-106°C. ANALYSIS: Calculated for C₁₀H₁₅N₃O: 62.15%C 7.82%H 21.74%N Found: 62.47%C 7.92%H 21.87%N EXAMPLE 3 4-[[(Diisopropylamino)methylene]amino]-3-pyridinol A mixture of 4-amino-3-pyridinol (3.0 g), N,N-diisopropylformamide dimethyl acetal (9.54 g) and 15 ml dry toluene was stirred at room temperature for 18 hours and thereafter heated to 60-70°C. After 90 minutes, the mixture was cooled to room temperature, concentrated in vacuo and chromatographed on silica using 10:90 CH₃OH/ethyl acetate as an eluent. The fractions containing the desired product were combined and concentrated to a thick oil, which solidified on refrigeration. This solid (5.3 g) was triturated with hexane three times to provide the product as a white solid, m.p. 77-79°C. ANALYSIS: Calculated for C₁₂H₁₉N₃O: 65.13%C 8.65%H 18.99%N Found: 65.17%C 8.65%H 19.02%N EXAMPLE 4 4-[[(1-Pyrrolidinyl)methylene]amino]-3-pyridinol dihydrochloride 4-Amino-3-pyridinol (2.5 g) was added to 1-pyrrolidinylformamide dimethyl acetal (20 ml), and the mixture was stirred at room temperature for a half hour and concentrated under high vacuum at 40-50°C. The oily residue was triturated twice from diethyl ether and recrystallized from ethyl acetate/diethyl ether to yield 2.76 g of solid. The solid was dissolved in a mixture of ethyl acetate (90 ml) and methanol (10 ml), the mixture was filtered to remove insolubles, and ethereal hydrogen chloride (50 ml) was added to the solution, whereupon 3.62 g of solid was obtained. This was recrystallized from methanol/diethyl ether and dried under high vacuum overnight to yield 2.16 g of product, m.p. 190°C (dec.). ANALYSIS: Calculated for C₁₀H₁₅Cl₂N₃O: 45.47%C 5.72%H 15.91%N Found: 45.05%C 5.88%H 15.73%N EXAMPLE 5 4-[[(1-Piperidinyl)methylene]amino]-3-pyridinol 4-Amino-3-pyridinol (3.3 g) was added to 1-piperidinylformamide dimethyl acetal (50 ml) and the mixture was stirred at 100°C until it became homogeneous (approximately one minute). The reaction mixture was cooled, and placed in an ice bath for a half hour. The crystallized product was filtered, washed well with diethyl ether, and air dried to yield 4.64 g of product. This was recrystallized from ethyl acetate and dried under high vacuum and refluxing ethanol overnight to yield 3.39 g of fluffy needles, m.p. 171-172.5°C. ANALYSIS: Calculated for C₁₁H₁₅N₃O: 64.37%C 7.37%H 20.47%N Found: 64.21%C 7.33%H 20.30%N EXAMPLE 6 4-[[(Hexahydro-1H-azepin-1-yl)methylene]amino]-3 - pyr idinol 4-Amino-3-pyridinol (6.0 g) was added to N-(hexahydro-1H-azepin-1-yl)-formamide dimethyl acetal (60 ml) and the mixture was stirred at room temperature for a half hour, placed in a 60°C oil bath and concentrated under high vacuum. The resulting oil was boiled in diethyl ether/pentane (1:1) (300 ml), and the solution was decanted, leaving behind a dark red residue. The solution was concentrated to 100 ml and cooled in an ice bath, and after addition of a few seed crystals, it was placed in a refrigerator overnight to yield 2.66 g of crystalline solid, m.p. 117-118°C. ANALYSIS: Calculated for C₁₂H₁₇N₃O: 65.73%C 7.81%H 19.16%N Found: 65.66%C 7.56%H 18.98%N EXAMPLE 7 4-[[(4-Morpholinyl)methylene]amino]-3-pyridinol 4-Amino-3-pyridinol (3.5 g) was added to 4-morpholinyl-formamide dimethyl acetal (50 ml) and the mixture was stirred at 100°C until it became homogeneous (approximately 3 minutes). The reaction mixture was cooled and placed in an ice bath for a half hour. The crystallized product was filtered, washed well with diethyl ether, and air dried to yield 5.14 g of product. This was recrystallized from methanol and dried under high vacuum and refluxing ethanol overnight to yield 3.89 g of crystals, m.p. 192-193°C. ANALYSIS: Calculated for C₁₀H₁₃N₃O₂: 57.96%C 6.32%H 20.28%N Found: 57.96%C 6.25%H 20.28%N EXAMPLE 8 4-[[(N-methyl-N-butylamino)methylene]amino]-3-pyridinol A mixture of 4-[[(dimethylamino)methylene]amino]-3-pyridinol (7.50 g), N-methylbutylamine (8.10 g), ammonium sulfate (0.600 g), and anhydrous toluene (25 mL) was heated at reflux under nitrogen for 2.25 hours. The solution was concentrated under reduced pressure and the crude product chromatographed on silica gel (10% methanol in dichloromethane) to afford 6.04 g of solid. Recrystallization from ethyl acetate/hexanes afforded 3.90 g of a crystalline material, m.p. 83-85°C. ANALYSIS: Calculated for C₁₁H₁₇N₃O: 63.74%C 8.27%H 20.27%N Found: 63.80%C 8.40%H 20.25%N EXAMPLE 9 4-[[(N-cyclohexyl-N-methylamino)methylene]amino]-3-pyridinol A mixture of 4-[[(dimethylamino)methylene]amino]-3-pyridinol (5.00 g), N-methylcyclohexylamine (5.20 g), and anhydrous toluene (50 mL) was heated at reflux under nitrogen for 17 hours. The solution was concentrated under reduced pressure and the crude product chromatographed on silica gel (10% methanol in dichloromethane) to afford 5.92 g of solid. Recrystallization from ethyl acetate/hexanes afforded 4.90 g of crystalline material, m.p. 127-129°C. ANALYSIS: Calculated for C₁₃H₁₉N₃O: 66.92%C 8.21%H 18.01%N Found: 66.69%C 7.91%H 17.89%N EXAMPLE 10 4-[[(4-Thiomorpholinyl)methylene]amino]-3-pyridinol A mixture prepared from 4-[[(dimethylamino)methylene]amino]-3-pyridinol (5.14 g), thiomorpholine (10.5 ml, distilled from CaH₂) and dry toluene (120 ml) was refluxed overnight. The reaction mixture was concentrated, triturated with diethyl ether, adhered to silica (methanol), flash chromatographed (10% methanol/ethyl acetate), and triturated with diethyl ether to yield 6.06 g of product. A 3.5 g sample was recrystallized from methanol, and dried under high vacuum and refluxing isopropanol to yield 2.13 g of crystals, m.p. 197-198.5°C. ANALYSIS: Calculated for C₁₀H₁₃N₃OS: 53.79%C 5.87%H 18.82%N Found: 53.75%C 5.84%H 18.69%N EXAMPLE 11 4-[[(Dimethylamino)methylene]amino]-3-pyridinyl methylcarbamate To a hot suspension of 4-[[(dimethylamino)methylene]amino]-3-pyridinol (7.0 g) in dry tetrahydrofuran (THF) were added sodium hydride (168 mg) and methyl isocyanate (2.6 ml). The reaction mixture was stirred at room temperature overnight, cooled in an ice-methanol bath and filtered. The solid was washed with diethyl ether and distributed between methylene chloride (250 ml) and saturated ammonium chloride (30 ml) and, extracted twice more with methylene chloride (200 ml). The solution was dried (MgSO₄) and concentrated and the solid was recrystallized from ethyl acetate and dried under high vacuum and refluxing ethanol to yield 6.18 g of crystals, m.p. 137-139°C. ANALYSIS: Calculated for C₁₀H₁₄N₄O₂: 54.04%C 6.35%H 25.21%N Found: 53.90%C 6.21%H 25.10%N EXAMPLE 12 4-[[(Dimethylamino)methylene]amino]-3-pyridinyl ethylcarbamate To a warm solution of 4-[[(dimethylamino)methylene]amino]-3-pyridinol (7.12 g) in dry tetrahydrofuran (150 mL) were added sodium hydride (173 mg) and ethyl isocyanate (3.59 mL). The reaction mixture was stirred at room temperature overnight, cooled in an ice bath and filtered, and the solid was washed with diethyl ether. The solid was distributed between methylene chloride (250 mL) and saturated ammonium chloride (30 mL) and extracted twice more with methylene chloride (100 mL). The solution was dried (MgSO₄) and concentrated, and the solid was recrystallized from ethyl acetate to yield 5.7 g of needles, m.p. 138°C (dec.). ANALYSIS: Calculated for C₁₁H₁₆N₄O₂: 55.92%C 6.83%H 23.71%N Found: 55.93%C 6.95%H 23.74%N EXAMPLE 13 4-[[(Dimethylamino)methylene]amino]-3-pyridinyl N,N-dimethylcarbamate 4-[[(Dimethylamino)methylene]amino]-3-pyridinol (1.65 g) was refluxed for 1 hour in 20 ml of benzene containing 1.10 g of Et₃N and 1.10 g of N,N-dimethylcarbamyl chloride. At the end of this time, the reaction mixture was applied directly to a silica column and eluted with 5% Et₃N/ethyl acetate. Concentration of the product-containing fractions gave 2.05 g of chromatographically pure product which was distilled in a bulb to bulb apparatus (oven temperature = 175°C) to give analytically pure material, m.p. 64-66°C. ANALYSIS: Calculated for C₁₁H₁₆N₄O₂: 55.91%C 6.83%H 23.71%N Found: 55.63%C 6.76%H 23.51%N EXAMPLE 14 4-[[(Dimethylamino)methylene]amino]-3-pyridinyl phenylcarbamate To a warm solution of 4-[[(dimethylamino)methylene]amino]-3-pyridinol (3.0 g) in dry tetrahydrofuran (60 mL) was added phenyl isocyanate (2.05 mL). The reaction mixture was stirred at room temperature for 1.5 hours and filtered. The solid was washed with dry diethyl ether, air dried, and dried under high vacuum and refluxing ethanol for 4 hours to yield 4.19 g of solid, m.p. 151°C. ANALYSIS: Calculated for C₁₅H₁₆N₄O₂: 63.37%C 5.67%H 19.71%N Found: 63.13%C 5.79%H 19.60%N EXAMPLE 15 4-[[(Dimethylamino)methylene]amino] - 3 - pyrid inyl piperidin-1-carboxylate A mixture prepared from 4-[[(dimethylamino)methylene]amino]-3-pyridinol (5.2 g), triethylamine (4.8 mL), piperidine carbonyl chloride (4.89 mL) and benzene (173 mL) was refluxed for a half hour, cooled, poured directly onto a silica column and eluted with 5% Et₃N/ethyl acetate to yield 7.55 g of product. Recrystallization from ethyl acetate and drying under high vacuum for 2 hours yielded 5.5 g of crystals, m.p. 90-91°C. ANALYSIS: Calculated for C₁₄H₂₀N₄O₂: 60.85%C 7.30%H 20.27%N Found: 60.78%C 7.45%H 20.17%N EXAMPLE 16 4-[[(Diethylamino)methylene]amino]-3-pyridinyl N,N-dimethyl carbamate To a solution prepared from 4-[[(diethylamino)methylene]amino]-3-pyridinol (3.12 g), triethylamine (3.34 g) and tetrahydrofuran (50 mL) was added N,N-dimethylcarbamyl chloride (2.28 g) under nitrogen. The resulting mixture was stirred at ambient temperature for 6 hours, diluted with ether (50 mL) and filtered. The filtrate was concentrated under reduced pressure and the residue chromatographed on silica gel (elution with 10% methanol in dichloromethane) to give 3.00 g of solid. Recrystallization from ether/hexanes afforded 1.57 g of crystalline solid, m.p. 73-74°C. ANALYSIS: Calculated for C₁₃H₂₀N₄O₂: 59.07%C 7.63%H 21.20%N Found: 59.06%C 7.82%H 21.16%N EXAMPLE 17 4-[[(Dipropylamino)methylene]amino]-3-pyridinyl N,N-dimethylcarbamate A mixture prepared from 4-[[(dipropylamino)methylene]amino-3-pyridinol (3.22 g), triethylamine (3.15 g), dimethylcarbamyl chloride (2.01 mL) and tetrahydrofuran (100 mL) was refluxed for 1 hour, cooled, poured directly onto a silica column and eluted successively with ethyl acetate and 5% Et₃N/ethyl acetate. The eluate was concentrated and the solid was recrystallized from diethyl ether to yield 2.99 g of product, m.p. 84-85°C. ANALYSIS: Calculated for C₁₅H₂₄N₄O₂: 61.62%C 8.27%H 19.16%N Found: 61.74%C 8.33%H 19.23%N EXAMPLE 18 4-[[(1-Pyrrolidinyl)methylene]amino]-3-pyridinyl N,N-dimethylcarbamate A mixture prepared from 4-[[(1-pyrrolidinyl)methylene]amino]-3-pyridinol (3.79 g), triethylamine (4.29 mL), dimethylcarbamyl chloride (2.74 mL) and tetrahydrofuran (130 mL) was refluxed for 1 hour, cooled, poured directly onto a silica column and eluted successively with ethyl acetate and 5% Et₃N/ethyl acetate. Recrystallization from ethyl acetate and drying under high vacuum and refluxing acetone for 4 hours yielded 3.55 g of crystals, m.p. 99-100°C. ANALYSIS: Calculated for C₁₃H₁₈N₄O₂: 59.53%C 6.92%H 21.36%N Found: 59.70%C 6.99%H 21.26%N EXAMPLE 19 4-[[(1-Piperidinyl)methylene]amino]-3-pyridinyl N,N-dimethylcarbamate A mixture prepared from 4-[[(1-piperidinyl)methylene]amino]-3-pyridinol (3.5 g), triethylamine (3.69 mL), dimethylcarbamyl chloride (2.3 mL) and tetrahydrofuran (130 mL) was refluxed for 2 hours, filtered, poured directly onto a silica column and eluted successively with ethyl acetate and 5% Et₃N/ethyl acetate to yield 4.49 g of product. Recrystallization from ethyl acetate and drying under high vacuum yielded 3.94 g of crystals, m.p. 88-89°C. ANALYSIS: Calculated for C₁₄H₂₀N₄O₂: 60.85%C 7.30%H 20.27%N Found: 60.90%C 7.44%H 20.13%N EXAMPLE 20 4-[[(Hexahydro-azepin-1-yl)methylene]amino]-3-pyridinyl N,N-dimethylcarbamate A mixture prepared from 4-[[(hexahydro-azepin-1-yl)methylene]amino]-3-pyridinol (2.9 g), triethylamine (2.86 ml), dimethylcarbamyl chloride (1.83 ml) and tetrahydrofuran (85 ml) was refluxed for 1 hour, cooled, poured directly onto a silica column and eluted successively with ethyl acetate and 5% Et₃N/ethyl acetate. The eluate was concentrated and dried under high vacuum to obtain 3.88 g of oil. The oil solidified in a refrigerator over the weekend, and was triturated with cold pentane to yield 3.31 g of solid, m.p. 68-70°C. ANALYSIS: Calculated for C₁₅H₂₂N₄O₂: 62.05%C 7.64%H 19.30%N Found: 61.86%C 7.55%H 19.20%N EXAMPLE 21 4-[[(4-Morpholinyl)methylene]amino]-3-pyridinyl N,N-dimethylcarbamate A mixture prepared from 4-[[(4-morpholinyl)methylene]amino]-3-pyridinol (3.04 g), triethylamine (3.19 mL), dimethylcarbamyl chloride (2.04 mL) and tetrahydrofuran (121 mL) was refluxed for 1 hour, cooled, poured directly onto a silica column and eluted successively with ethyl acetate and 5% Et₃N/ethyl acetate. Recrystallization from ethyl acetate (50 mL) and drying under high vacuum and refluxing acetone overnight yielded 3.04 g of fluffy needles, m.p. 127-129°C. ANALYSIS: Calculated for C₁₃H₁₈N₄O₃: 56.10%C 6.52%H 20.13%N Found: 56.10%C 6.84%H 20.16%N EXAMPLE 22 4- [[(Dimethylamino)methylene]amino]-3-pyridinyl N,N-diethylcarbamate 4-Amino-3-pyridinol N,N-diethylcarbamate (5.80 g) was refluxed for 30 minutes in 50 mL of N,N-dimethylformamide dimethyl acetal. At the end of this time the reaction mixture was concentrated under reduced pressure and the residue was purified by flash chromatography (5% Et₃N/ethyl acetate) to give, after concentration of the product-containing fractions, 4.63 g of chromatographically pure product. An analytically pure material was obtained by recrystallizatin from Et₂O, m.p. 67-69°C. ANALYSIS: Calculated for C₁₃H₂₀N₄O₂: 59.07%C 7.62%H 21.20%N Found: 59.27%C 7.50%H 21.25%N EXAMPLE 23 4-[[(Dihexylamino)methylene]amino]-3-pyridinyl N,N-dimethyl carbamate maleate To a stirred mixture of 4-[[(dihexylamino)methylene]amino]-3-pyridinol (3.30 g) and triethylamine (2.3 ml) in 75 ml dry Et₂O was added dimethyl carbamyl chloride (1.2 ml). The mixture was stirred at room temperature for 18 hours, after which no starting material remained as seen by TLC (silica, 10:90 CH₃OH:CH₂Cl₂). The mixture was diluted with Et₂O, filtered, and the filtrate concentrated in vacuo and chromatographed on silica using EtOAc eluent. The fractions containing desired product were combined and concentrated to an oil. The maleate salt was prepared in isopropanol, concentrated to dryness, and recrystallized from CH₂Cl₂/Et₂O/hexane to provide 2.43 g of the product as a white solid, m.p. 123-125°C. ANALYSIS: Calculated for C₂₅H₄₀N₄O₆: 60.96%C 8.18%H 11.37%N Found: 60.84%C 8.23%H 11.36%N EXAMPLE 24 4-[[(Diisopropylamino)methylene]amino]-3-pyridinyl N,N-dimethyl carbamate To a stirred mixture of 4-[[(diisopropylamino)methylene]amino]-3-pyridinol (1.06 g) and triethylamine (1.0 ml) in 25 ml dry Et₂O was added dimethyl carbamyl chloride (0.53 ml). The mixture was stirred at room temperature for 2 hours, after which no starting material remained as seen by TLC (silica, 10:90 CH₃OH:CH₂Cl₂). The mixture was diluted with 25 ml Et₂O, filtered, washed with Et₂O, and the filtrate concentrated in vacuo and chromatography on silica using EtOAc eluent. The fractions containing desired product were combined and concentrated to provide 500 mg of pure product. Another run was carried out in the same manner as above using 740 mg of starting material. The products from both runs were combined. Recrystallization attempts failed, and the product was dried in vacuo to provide 790 mg of a white solid, m.p. 76-79°C. ANALYSIS: Calculated for C₁₅H₂₄N₄O₂: 61.62%C 8.27%H 19.16%N Found: 61.63%C 8.27%H 18.82%N EXAMPLE 25 4-[[(N-methyl-N-butylamino)methylene]amino]-3-pyridinyl-N,N-dimethyl carbamate maleate To a stirred solution of 4-[[(N-methyl-N-butylamino)methylene]amino]-3-pyridinol (2.88 g), triethylamine (2.11 g), and tetrahydrofuran (40 mL) under nitrogen was added N,N-dimethylcarbamyl chloride (1.99 g). The reaction mixture was stirred at ambient temperature for 17 hours, diluted with ether (25 mL), and filtered. The filtrate was concentrated under reduced pressure and the residue chromatographed on silica gel (elution with 10% methanol in dichloromethane) to give 2.41 g of an amber liquid. The liquid was dissolved in isopropanol (25 ml) and a solution of maleic acid (1.00 g) in isopropanol (15 mL) was added. The resulting solution was concentrated under reduced pressure to give a beige solid. Recrystallization from dichloromethane/ethyl acetate afforded 1.37 g (25.0%) of a white powder, m.p. 130-133°C. ANALYSIS: Calculated for C₁₈H₂₆N₄O₆: 54.81%C 6.64%H 14.20%N Found: 54.87%C 6.60%H 13.97%N EXAMPLE 26 4-[[(N-methyl-N-cyclohexylamino)methylene]amino]-3-pyridinyl N,N-dimethyl carbamate maleate To a solution of 4-[[(N-methyl-N-cyclohexylamino)methylene]amino]-3-pyridinol (2.33 g), triethylamine (1.74 g) and tetrahydrofuran (30 mL) under nitrogen was added N,N-dimethylcarbamyl chloride (1.40 g). The reaction mixture was stirred at ambient temperature for 24 hours, diluted with ether (20 mL) and filtered. The filtrate was concentrated under reduced pressure and the residue chromatographed on silica gel (elution with 10% methanol in dichloromethane) to give 2.25 g of an amber liquid. The liquid was dissolved in isopropanol (20 ml) and a solution of maleic acid (0.866 g) in isopropanol (15 mL) was added. The resulting solution was concentrated under reduced pressure to give a beige solid. Recrystallization from dichloromethane/ethyl acetate afforded 2.37 g of a white crystalline solid, m.p. 157-159°C. ANALYSIS: Calculated for C₂₀H₂₈N₄O₆: 57.13%C 6.71%H 13.32%N Found: 57.40%C 6.75%H 13.34%N EXAMPLE 27 4-[[(N-Benzyl-N-methylamino)methylene]amino]-3-pyridinyl N,N-dimethylcarbamate sesquifumarate 4-[[(Dimethylamino)methylene]amino]-3-pyridinol (3.0 g) was refluxed in N-benzyl-N-methylamine (6.12 ml) and dry toluene (60 ml) overnight. The reaction mixture was concentrated, adhered to silica (MeOH), flash chromatographed (10% MeOH/EtOAc) and concentrated to give 4.4 g of 4-[[(N-benzyl-N-methylamino)methylene]amino]-3-pyridinol. 3.93 g of the pyridinol was refluxed with triethylamine (3.52 ml), dimethylcarbamyl chloride (2.25 ml) and THF (100 ml) for one hour. The reaction mixture was poured directly onto a silica column and eluted successively with EtOAc and 5% Et₃N/EtOAc, and the eluate was concentrated to obtain 4.36 g of an oil. The oil (4.02 g) was dissolved in 25 ml of boiling ethyl acetate, and a solution of fumaric acid (1.64 g) in 20 ml of methanol was added, followed by the addition of 5 ml of pentane. 2.99 g of the sesquifumarate was collected as a white solid, m.p. 146-147°C. ANALYSIS: Calculated for C₁₇H₂₀N₄O₂·C₆H₆O₆: 56.78%C 5.39%H 11.52%N Found: 56.80%C 5.44%H 11.18%N EXAMPLE 28 4-[[(4-Thiomorpholinyl)methylene]amino]-3-pyridinyl N,N-dimethylcarbamate A mixture of 4-[[(4-thiomorpholinyl)methylene]amino]-3-pyridinol (3.28 g), triethylamine (3.17 ml) and dimethylcarbamyl chloride (2.03 ml) in THF (100 ml) was refluxed for 1.25 hours, cooled, poured directly onto a silica column and eluted successively with EtOAC and 5% Et₃N/EtOAc. The eluate was concentrated and triturated with diethyl ether. Recrystallization from ethyl acetate and drying under high vacuum and refluxing ethanol overnight yielded 2.92 g of white needles, m.p. 155.5-156°C. ANALYSIS: Calculated for C₁₃H₁₈N₄O₂S: 53.04%C 6.16%H 19.03%N Found: 52.93%C 6.21%H 18.84%N

Claims: Claims for the following Contracting States : DE, GB, FR, IT, NL, SE, LI, CH, BE, AT, LU, DK A compound of the formula I where R₁ is (C₁-C₆)alkyl and R₂ is (C₁-C₆)alkyl, cyclo(C₃-C₇)alkyl or aryl(C₁-C₆)alkyl; wherein the term aryl is a phenyl group substituted with 0, 1 or 2 substituents which are each independently (C₁-C₆)alkyl, (C₁-C₆)alkoxy, halogen or trifluoromethyl; or alternatively the group as a whole is and R₃ is hydrogen, wherein R₆ is hydrogen, (C₁-C₆)alkyl or phenyl, and R₇ is hydrogen or (C₁-C₆)alkyl, or a pharmaceutically acceptable acid addition salt thereof. A compound as defined in claim 1, where R₁ and R₂ or the group as a whole is as defined in claim 1, R₃ is hydrogen, where R₆ is (C₁-C₆)alkyl or phenyl and R₇ is hydrogen or (C₁-C₆)alkyl. A compound as defined in claim 2, where R₁ and R₂ are independently (C₁-C₆)alkyl, or the group as a whole is R₃ is hydrogen or where R₆ is (C₁-C₆)alkyl and R₇ is hydrogen or (C₁-C₆)alkyl. A compound as defined in claim 3, where R₁ and R₂ are independently (C₁-C₆)alkyl, and R₃ is where R₆ is hydrogen or (C₁-C₆)alkyl and R₇ is (C₁-C₆)alkyl. The compound as defined in claim 1, which is 4 [[(dimethylamino)methylene]amino]-3-pyridinyl-N,N-diethylcarbamate or a pharmaceutically acceptable acid addition salt thereof. The compound as defined in claim 1, which is 4[[(dimethylamino)methylene]amino]-3-pyridinyl ethylcarbamate, or a pharmaceutically acceptable acid addition salt thereof. A pharmaceutical composition which comprises a compound as defined in any one of the preceding claims as the active ingredient and a suitable carrier therefor. Use of a compound as defined in any one of the preceding claims for the preparation of a medicament having memory dysfunction alleviating activity. A process for the preparation of a compound as defined in claim 1, which comprises a) reacting a compound of the formula with a compound of the formula IIa or IIb where R₁ and R₂ are as defined and represents a group of the formulae to form a compound of the formula I, where R₃ is hydrogen and R₁ and R₂ or the group as a whole is as defined above, or b) optionally reacting a compound of the formula I, where R₃ is hydrogen and R₁ and R₂ are methyl, with an amine of the formula IVa or IVb where R₁ and R₂ are as defined above, but are not both methyl, and is as defined above, to form a compound of the formula I, where R₃ is hydrogen, and R₁ and R₂ are as defined above, but are not both methyl, or the group where is as defined above, c) optionally reacting a compound of the formula I, where R₃ is hydrogen and R₁ and R₂ are as defined or the group as a whole is as defined above, with an isocyanate of the formula O=C=N-R₇ where R₇ is as defined, to form a compound of the formula I, where R₁ and R₂ are as defined or the group as a whole is and R₃ is d) optionally reacting a compound of the formula I, where R₃ is hydrogen and R₁ and R₂ are as defined or the group as a whole is as defined above, with a compound of the formula VIa or VIb where R₆ and R₇ are as defined, but R₆ is not hydrogen and is to form a compound of the formula I, where R₃ is where R₆ and R₇ are as defined, but R₆ is not hydrogen, or where is as defined, and R₁ and R₂ are as defined or the group as a whole is as defined above, e) optionally reacting a compound of the formula Xc where R₆' and R₇' are independently (C₂-C₆)alkyl, with a compound of the formula where R₁ and R₂ and are as defined above, to form a compound of the formula I where R₃ is the group where R₆' and R₇' are each independently a (C₂-C₆)alkyl and R₁ and R₂ are as defined or the group as a whole is as defined above. Claims for the following Contracting States : ES, GR A process for the preparation of a compound of the formula I where R₁ is (C₁-C₆)alkyl and R₂ is (C₁-C₆)alkyl, cyclo(C₃-C₇)alkyl or aryl(C₁-C₆)alkyl; wherein the term aryl is a phenyl group substituted with 0, 1 or 2 substituents which are each independently (C₁-C₆)alkyl, (C₁-C₆)alkoxy, halogen or trifluoromethyl; or alternatively the group as a whole is and R₃ is hydrogen, wherein R₆ is hydrogen, (C₁-C₆)alkyl or phenyl, and R₇ is hydrogen or (C₁-C₆)alkyl, or a pharmaceutically acceptable acid addition salt thereof, which comprises a) reacting a compound of the formula with a compound of the formula IIa or IIb where R₄ and R₅ are as defined and represents a group of the formulae to form a compound of the formula I, where R₃ is hydrogen and R₁ and R₂ or the group as a whole is as defined above, or b) optionally reacting a compound of the formula I, where R₃ is hydrogen and R₁ and R₂ are methyl, with an amine of the formula IVa or IVb where R₁ and R₂ are as defined above, but are not both methyl, and is as defined above, to form a compound of the formula I, where R₃ is hydrogen, and R₁ and R₂ are as defined above, but are not both methyl, or the group where is as defined above, c) optionally reacting a compound of the formula I, where R₃ is hydrogen and R₁ and R₂ are as defined or the group as a whole is as defined above, with an isocyanate of the formula O=C=N-R₇ where R₇ is as defined, to form a compound of the formula I, where R₁ and R₂ are as defined or the group as a whole is and R₃ is d) optionally reacting a compound of the formula I, where R₃ is hydrogen and R₁ and R₂ are as defined or the group as a whole is as defined above, with a compound of the formula VIa or VIb where R₆ and R₇ are as defined, but R₆ is not hydrogen and is to form a compound of the formula I, where R₃ is where R₆ and R₇ are as defined, but R₆ is not hydrogen; or where is as defined and R₁ and R₂ are as defined or the group as a whole is as defined above, e) optionally reacting a compound of the formula Xc where R₆' and R₇' are independently (C₂-C₆)alkyl, with a compound of the formula where R₁ and R₂ and are as defined above, to form a compound of the formula I where R₃ is the group where R₆' and R₇' are each independently a (C₂-C₆)alkyl and R₁ and R₂ are as defined or the group as a whole is as defined above. A process as defined in claim 1, where R₁ and R₂ or the group as a whole is as defined in claim 1, R₃ is hydrogen, where R₆ is (C₁-C₆)alkyl or phenyl and R₇ is hydrogen or (C₁-C₆)alkyl. A process as defined in claim 2, where R₁ and R₂ are independently (C₁-C₆)alkyl, or the group as a whole is R₃ is hydrogen or where R₆ is (C₁-C₆)alkyl and R₇ is hydrogen or (C₁-C₆)alkyl. A process as defined in claim 3, where R₁ and R₂ are independently (C₁-C₆)alkyl, and R₃ is where R₆ is hydrogen or (C₁-C₆)alkyl and R₇ is (C₁-C₆)alkyl. The process as defined in claim 1, wherein 4[[(dimethylamino)methylene]amino]-3-pyridinyl-N,N-diethylcarbamate or a pharmaceutically acceptable acid addition salt thereof is prepared. The process as defined in claim 1, wherein is 4[[(dimethylamino)methylene]amino]-3-pyridinyl ethylcarbamate, or a pharmaceutically acceptable acid addition salt thereof is prepared. Use of a compound as defined in any one of the preceding claims for the preparation of a medicament having memory dysfunction alleviating activity.

Inventors: HRIB NICHOLAS JOSEPH, JURCAK JOHN GERARD, KAPPLES KEVIN JAMES, SHUTSKE GREGORY MICHAEL, TOMER JOHN DICK, HRIB, NICHOLAS JOSEPH, JURCAK, JOHN JOHN, KAPPLES, KEVIN JAMES, SHUTSKE, GREGORY MICHAEL, TOMER, JOHN DICK
Applicants: HOECHST ROUSSEL PHARMA, HOECHST-ROUSSEL PHARMACEUTICALS INCORPORATED
Application year: 1991
Main classification: C07D213
IPC codes: A61K31, A61P25, C07D213