TW487710B - Substituted 1,2,4-triazolo[3,4- a]pyridazine - Google Patents

Abstract

A substituted triazolopyridazine derivative, its use in therapy, compositions containing it and processes for its manufacture are disclosed. 3-(5-Methylixoxazol-3-yl)-6-(1-methyl-1,2,3-triazol-4-yl)methyloxy-1,2,4-triazolo[3,4-a]phthalazine. A pharmaceutical composition for use in treating a dementing illness comprising the compound as described in claim 1 and a pharmaceutically acceptable carrier.

Description

487710 A7 B7 V. Description of the invention (1) The present invention relates to a substituted triazolium-dachin derivative, its therapeutic use I, a composition containing the same, and a preparation method thereof. We have now found that agents that achieve cognitive enhancement are feasible and can be used with benzodiazepine receptors or diametrically opposite agonists to have fewer previously described spasmodics The danger of effect. The preferred inverse agonist is the opposite agonist to the α5 receptor and is relatively inactive at the α1, α2, and α3 receptor binding sites. European patent applications 0085840 and 〇1; 34946 describe a related series of 1,2,4-triazolium [3,4-a] 2,3-phthalocyanine derivatives, which have an anxiolytic activity. However, there are no descriptions or suggestions for the compounds of the present invention or the compounds disclosed in the application with any enhanced properties of tolerance. The present invention provides a compound, which is: 3- (5-methyliso4-4--3-yl) -6- (1-methyl-1,2,3-trisene-4-yl) methyloxy Base-1,2,3 -San Junyi [3,4-a]. Shows cognitive enhancement as reported by McNamara and Skelton in Psychobiology, 21 · 101-108. (Please read the precautions on the back before you fill out this page to test compounds in the Morris water maze. The functional potency of different receptor subtypes can be disclosed in World Patent-A-9 6 2 5 9 4 8 Therefore, 'for example' the compounds of the present invention can be used in a variety of central nervous system diseases. This disease includes delusions, dementia and forgetfulness and other cognitive diseases. Examples of delusions are delusions caused by substance poisoning or substance withdrawal, caused by a variety of The delusions caused by the cause * N0s (not detailed). Examples of dementia are: Alzheimer's (A1 zhe 丨 ^ er 's) type of dementia that started early-4 i, Paper scale towel | _ 纟: M (~ ^ Λ4 specifications (--- 487710 A7 B7 V. Description of the invention (2 It can be without concurrent disease or delusion, fantasy or depression = Zheimer's type thin Stay, which can be without concomitant disease or delusion, fantasy; = mood; Dementia caused by head injury &dementia; Leanness caused by Parkinson's disease; Dementia caused by Huntington's (H = ngton, s) disease; Sickness by Beck's disease ; Catty; into "dementia; Creutzfeld_

Jakob), caused by dementia; perpetuated by material slander or by multiple :: 1 :, dementia; and NOS dementia. An example of amnesia is permanent amnesia that is induced by features or material slander or is it deleted? A hydrazine ... compound comprising a compound of the present invention and a pharmaceutically acceptable carrier is preferably a unit dosage form, such as a lozenge, a powder, a granule, a sterile parenteral solution or a suspension type F aerosol or Liquid sprays, drops, ampoules, percutaneous injection equipment or suppositories; it is administered orally, parenterally, intranasally, = anally, or by inhalation or insufflation. In the preparation of solids such as bonding agents, the main active ingredients are mixed with a pharmaceutical carrier, and the tableted ingredients such as corn powder, lactose, sucrose, and sucrose I talc, Stearic acid, magnesium stearate, glutarol, or gum = active agent, such as sorbitol monooleate, polyethylene glycol, and diluents on it, such as water, to form a composition comprising the present invention Compound or compound; a pre-formulation composition that may accept a homogeneous mixture of cultural salts. When referring to these 2 previous formula compositions as homogeneous, it means that the active ingredients are evenly distributed :: cloth so that the composition can be easily subdivided into equal effective unit doses, including two (2) (Please fill in this page again)

-5- A7 B7 V. Description of the invention (3 lozenges, pills and capsules. Therefore, the solid front left M-shirt is subdivided into the above composition into the above: bit, type 2 which contains 0 "to about 500 mg of the present invention Active ingredients. Codex I early-stage agent type 1 contains i to 1000 mg, such as 1, 2, 5 'i 0, 25, 50, or 1000 mg of active ingredient. It is novel or combined in a novel way. Group, substance, or pill to produce a dosage form that has the benefit of prolonged action. For example, a 'dose or pill can contain internal and external drug components, while the latter is a film type on top of the former. These two components can Used to prevent disintegration in the stomach and allow the internal components to enter the duodenum dull or delay the release of the enteric layer. A variety of substances can be used for this enteric layer or coating. For example, a mixture of shellac, cetyl alcohol, and cellulose acetate. Liquid forms in which the novel composition of the present invention is administered orally or by injection include aqueous solutions, suitably flavored, water or oil suspensions, and flavored emulsions such as Of cottonseed oil, sesame oil, coconut oil or peanut oil Edible oils and similar pharmaceutical vehicles. Suitable dispersions or tinctures for use in aqueous suspensions include synthetic and natural gums such as tragacanth, acacia gum, alginate, I-glucose, sodium methylcellulose , Methylcellulose, polyvinylpyrrolidone or gelatin. The present invention further provides the use of a compound of the present invention for the manufacture of enhanced tolerance, preferably in humans suffering from amnesia such as Alzheimer's disease A suitable dose for enhancing cognition is about 0.00 to 2.5 mg / kg per day, preferably about 0.01 to 100 g / kg per day, and especially about 0.01 to 5 g / kg per day. The compound can be ingested J to 4 times a day-6- see the grid (210X297 ^^ · I-- (read the precautions on the back before filling in this page) Order # 经 消 部 中心 楛 尊 ^ 巧 工 消贽 Cooperative private printing of the Ministry of Economy ’s final standards and only eliminates the printing of cooperatives and invention descriptions. However, in some cases, 7i ^ doses outside these ranges can be used. The invention of the chemical compound phase is based on, for example, the pestle and mortar or industrial phase. The temple foot is graduated to 1 to 10 microns, and the size of 罘 g is less than 5 microns. The compound can be known in the art, or, for example, in the Wu Guo patent- Α- 5 1 4 5 6 s 4 unveiled the first, and _ #j,. Thing < method, which includes methylation

], Lithium methyl disilazide and 3- (5-methyl its u Q fluorenyl isoformazole-3_yl) -6_ (Hl, 2,3_diazolium_5_yl) methyloxyphthalide Tillage response. The diazolidine [3,4, reaction is generally carried out in a solvent such as DMF, usually at a temperature lower than that of the reaction and then warmed to about room temperature, and is generally carried out under an atmosphere such as nitrogen. The reaction mixture is usually allowed to stand for 4-12 hours. The desired product is generally purified from other reaction products using conventional separation techniques, such as preparative HPLC. The compounds according to the present invention are effective in inhibiting the binding of [3H] -flumazenil to the benzodiazepine binding site of the human GABAa receptor containing α5 subunits stably expressed in Ltk cells. The compound of the accompanying example was tested by the above-mentioned analytical method, and it was found that [3H] R〇 1 5-1 78 8 was replaced by 1 値 ^ 1 〇 Ο η Μ or less of the human face GABAa receptor. Compounds of the present invention have been shown to enhance cognition in rat labyrinths (Morris, Learning and Stimulation, 1981, IX 23 9ff). Going further—Details of the method for enhancing cognition of the present invention can be found in ^^ patent 丄 ΑγΜ2 ^ ±. It has been stated that at the lowest effective dose of 0.3 mg / kg, the compound is known to occupy 40% of the receptor. It is also stated at a dose of 3 g / kg. This paper is in the standard of Sichuan Chuanzhong® Valve. (RNS) Λ4 size (210X 297 cm) ^^^ Tight clothing 1T (Please read the precautions on the back before filling this page} 487710 A7 B7 V. Description of the invention ( 5) The compound of the present invention can be produced as shown in the following example. The precise details of the reaction conditions and the significant improvement of the reaction steps are within the ability of those skilled in the art. (Please read the notes on the back before filling this page) Intermediate 1 6-Chloro- 3_ (5 · methylisosakishoki) -Sanjun 弁 [3-4_called gTaipa a) 1_Chloro-4-hydrazinophthalein 1,4-dichloro Phthalide (20.0 g, 0.100 mol) was added to a boiling solution of hydrazine monohydrate (3 7.3 ml, 0.765 mol) in ethanol (500 ml), and the mixture was heated at reflux for 0.5 hours. . The mixture was cooled to room temperature and the solid was collected by filtration and washed with ether. This was dissolved in n-butanol and ammonia (specific gravity 0.9 1) and heated until the solids were dissolved. The organic layer was separated, the residue was azeotroped (X 2) with toluene and evaporated in the thallium to produce the title hydrazine (11.5 g, 59%), 4 NMR (25 0 MHz, d ~ DMSO) 57.84 -8.04 (3H? M, Ar-H), 8.20 (1H, m, Ar-H); MS (ES +) m / e 194 [MH] +. b) 6-methylisoxazol-3-carboxylic acid is the central sample of the Ministry of Economic Affairs, and only _τ 消 贽 合 竹 社 印 $ Acetoacetone (10 g, 88 mmol) and nitric acid (specific gravity 1.4 2) / water (2: 3) (50 ml) was carefully added to reflux in a nitrogen stream and boiled for 1 hour. The solution was cooled to room temperature and aged overnight. The resulting solid was collected by filtration, washed with cooling water (2 X 7 ml) and hexane, and dried in the air to produce the title acid (4.4 g, 40%), 4 NMR (CDC13) S2.50 (3H5 d, J 2 0.8 Hz, Me), 6.41 (1Η, d, J = 0.8Hz, Ar-H) 0 c) 6-chloro-3-(5-methylisohumidazole-3 -yl) -12,4- Triazolium (3, j-al 8 Taipjing-8- paper scales) Chengzhou Middle Valve Family Standard ((, NS) A4WL grid (210/297 cm)) Central Standard of Ministry of Education ^ y AA7, B7 printed by the cooperative. V. Description of the invention (6) 'At 0 ° C, nitrogen, 5_methylisopurazol_3 • carboxylic acid (524 g' 41.3¾ mole), bis (2 —Oxyl-3-4 alkyl) phosphinylphosphonium chloride (10.5 g, 41.2 mmol) and triethylamine (115 ml, 82.5 mmol) were added to methylene chloride (1 liter) ^ Chloro-4-hydrazinophthalocyanine (8. 00 g '4 1 · 2 mmol) in a stirred suspension. The mixture was stirred at 0 for 2 hours and overnight at room temperature. The solvent was evaporated in the air, leaving a residue The product was ground with water and then the solid was taken out, washed with hexane and dried in the air to produce hydrazine (11 g), MS (ES +) m / e 3 04 [MH] +. A solution of ketohydrazine (11 g) and triethylamine hydrochloride (2.2 g, 20% by weight) in xylene (500 ml) was heated at reflux for 3 hours. The mixture was cooled to room temperature. Warmly read the effervescent agent in the stand. The residue was dissolved in dichloromethane, washed with water (X 2), dried (Mg SO 4) and evaporated in the air. The solid was recrystallized (dichloromethane / hexane). Alkane) to give the title compound (6.8 g, 58%), 1HNMR (3 60 megahertz, 00113) 52.59 (311, 3, 1 ^), 6.90 (111, 3, 8H)? 7.95 (1H ? m? Ar-H) 5 8.0 7 (1 H? m? Ar-H)? 8.34 (1Η, m, Ar-H), 8.78 (1H, s, Ar-H); MS (ES +) m / e 28 6 [MH] +. Reference example 1 on U .. Pyridine and Methoxy-124_triazolium f3,4-algjc produced by formazan, cultivated at room temperature under nitrogen, sodium hydride (244 mg of a 60/60 dispersion in oil '6.10 mol) was added with 2-pyridylmethanol (4 70 mg, 4.27 mmol) in dmP (60 ml). In the solution), the mixture was stirred for 0.2 5 hours. After that, the intermediate j (j 160 mg, 4.0 mmol) was used. -9-Paper ruler / iUW] Min valve home standard ((, NS) 8 4 specifications (210X 297 Gongchu) -------- install ------ order ----- (Please read the precautions on the back before filling (This page) 487710 A7 B7 V. Description of the invention (7) ~ · Add and stir the mixture for 2 hours. The solvent was removed in the air and the residue was dissolved in dichloromethane, washed with water (χ 2), dried (MgS0j and evaporated in the air. Flash chromatography was performed on a silica gel at 3 0 / 〇 Formic acid / dichloromethane was dissociated, followed by recrystallization (dichloromethane / hexane) to give the title product (64 mg, 44%), melting point 23 4-23 6. C, 1HNMR (3 60 megahertz 'CDC13) S2.59 (3H, d, J = 0.8 Hz, Me), 5.77 (2H, s, CH2), 6.82 (1Η, d, J = 0.8HZ, A ·· Η), 7.30 ( 1Η, m, Ar-H), 7.74-7.8 5 (3 H, m, Ar-H), 7.95 (1Η, m, Ar_H), 8.33 (lH, d, J = 7.8HZ, Ai * -H ), 8.64-8.72 (2H, m, Ar-H); MS (ES +) m / e 3 5 9 [MH] +; Analytical measurement 値 C, 62.93; H, 3.56; N, 22.94. C19H14N6〇2 0.0 5 (CH2Cl2) Theoretical ， c, 63.10; H, 3.9 2; N, 2 3 · 17%. Refer to Example 2 for a group) Methyl gas, a methylisopurinium 33_ group) "3,4 -algJc The title compound was prepared from the intermediates i and 2-bromopyridine-6-methanol (tetrahedron 1 996, 50, 2 5 3 7) by the method of Reference Example 1. The product was isolated by adding water to the reaction mixture and filtering off the obtained Shen Dianwu from 4. Isolated with ethyl acetate on silica gel by flash chromatography and recrystallized (ethyl acetate-methanol) to give the title phthalocyanine, melting point 247.5 -249 ° C; 4 NMR (360 megahertz, CDCl3) S2 61 ( 3H, d, J = 〇7Hz, M magic, 5 73 (2H, s, Ch2), 6.82 (1H, d, J = 0.7HZ, Ar-H), (1 H, d, J-7 · 8 H z, A r-H), 7 · 6 3 (1 H, t, J = 7 · 7 H z, -10-rNS) (2i〇xi ^ y ----: 丨-: ----- ---, 玎 ----- Refer to (阅读 Please read the notes on the back before filling in this page) Printed by the Central Standards Bureau of the Ministry of Economic Affairs, only a consumer cooperative 487710 A7 _______B7 V. Description of the invention (8) A Η), 7.76 (1Η, d, J = 7.4Hz, Ar-H), 7.84 (1Η, t, J = 8.4ttz, Ar-H), 7.98 (1H, t, J = 8.4Hz5 Ar-H) , 8.31 (1Η, d, J = 8.5Hz, Ar-H), 8.70 (1H, d, Ar-H); MS (ES +) m / e 43 7 [MH] +, · Measured and measured 値 c , 52.27; H, 2.85; N, 19.14. C19H13N6O2Br. 0.1 (H2O) Theory 値 C, 51.98; H, 3.03; N, 18.60%. -3- (5-azole-3-yl) -1.2,4 -Triazole 弁 π, 4-1 Phthalogon dissolves sodium hydroxide (067 g, 17 mmol) in water (7.5 ml) Add to a stirred solution of dioxin (3 7.5 ml) intermediate (丨. G, 3.5 mmol) and heat the mixture at reflux for 4 hours. Evaporate the solvent in the air to leave the residue It is distributed between water and diethyl ether. The water layer is separated, washed with ether (X 1) and acidified with 2N hydrochloric acid to reach pH 2. The solid produced by Shen Dian in the solution is filtered, and the solution is filtered with dichloride Carbohydrate extraction (X 3). Dry (M g S Ο 4) combined extracts were evaporated in the air and combined with precipitates to yield the title product (0.45 g, 48%), 4 NMR (250 megahertz) d, DMSO) 52.58 (3H, d, J = 0.7HZ, Me), 7.07 (lH, d, J = 0.9Hz, Ar-H), 7.94 (1 (, m, Ar-H), 8. 〇8 (lH, m, At-H), 8.24 (1H, d, J = 7.4HZ, Ar-H), 8.54 (1H, d, J = 7.4Hz, Ar-H), 13.32 ( 1Η, br s, NH); MS (ES +) m / e 268 [MH] +. Reference Example 3 Isoxazole-3 -yl) -6 (1 Η -1,2,3 triazole #-5-I 、 甲 __ -11-Wood paper scale Shizhou Chinese storehouse standard (^ s 7m «L ^ (210X 297 ^ f) '"τ; ^ I ------, 1τ ----- (Please read the notes on the back before filling this page) 487710 Α7 Β7 V. Description of the invention (9-based A-based 1,2,4- pingshang 幷 "3,4-alBj: Geng a) 5 · Methyl-1 v 丨 2 · Di. (Dimethyxyl) ethoxy " [A certain _i, 2,3_triamidine in -78 C 'under nitrogen' Zhi n-butyl I (6.8 ml of a 1. 6 Μ solution in hexane, 1 0.9 mol) 〇 · 0 8 hours dropwise to 1- [2- (trimethyl-silyl) ethoxy] methyl contained in THF (30 ml) · 152,3 -Sanjun and (J. Heterocycl Chem ·, 1992 29 1 203) (2.077 g, 10.42 mmol). The gluten solution was warmed to -6 0 C 'over 067 hours, and then cooled to -7 8 to d MF (0 9 ml, 1 1.6 mmol). Warm the mixture to room temperature and stir for an additional 6.5 hours. Add saturated chloride solution (50 ¾ liters) and extract with diethyl ether (3 X 80 ¾ liters) . The combined ether extracts were dried (MgS04), dried in the air, and the residue was chromatographed on Shixi gel. It was dissolved in 30% ethyl acetate / hexane to produce the title Sanjun (1.713 g, 72%) ), IH NMR (3 60 megahertz) CDCl3) 50.01 (9H, s, M ^ Si), 0.92-0 · 99 (2Ηm, CH2), 3.64-3 · 69 (2Η, m, CH2) , 6.0 · 5 (2Η, s, CH2), 8.31 (1H, s, Ar-H), 1 ·· 2 (1Η, s5 CH0). B) Silyl) Ethyl 1-methyl榡 ^^ θ, τ. Printed by the Consumer Cooperatives (Read the precautions on the reverse side and then fill out this page). 1,2,3-triazolium chloride at 0 ° C, nitrogen, sodium tetrahydroborate ( (0284 g, 7.51 millimoles) was added and stirred; the aforementioned triazolium (1.704 g, 7.4 95 pens) in methanol (8 ml) was dropped. The mixture was stirred at 0 for 5 hours and then at room temperature for 0.5 hours. Water was added to the mixture and distributed between dichloromethane and saturated brine. The aqueous layer was separated and taken up again with dichloromethane. Gan-12- wood-paper / M Ml towels 彳 彳: county Γ ^ Τμ specifications (210x ^ 75 ^ 487710 A7 B7) Ministry of Economic Affairs Ministry of Standards and Technology Bureau only two consumer cooperation private seals 5. Description of invention (10) The combined organic layers were dried (MgS04) and evaporated in the air, and the residue was purified on silica gel! Chromatography and dissociation with 70% ethyl acetate gave the title product (13 4 g, 78%), 4 NMR (3 60 megahertz, CDCl3) 5000 (9H, s, Me3Sl), 0.90.95 (2Η, m, Ch2), 3.58_3.63 (2H, 'm, CH2), 4.84 (2H, s , CH2), 5 8 0 (2H, s, CIi2) 7.68 (1Η, s, Ar-H). 'Methyl isofluorene: azole-3 diyl) -6 · υ2_ (trimethylsulfonium I碁 1 methyl-1,2,3 -trimodal 幷 -5 methyloxy 某-丄 幷 "3,4-al phthalocyanine title compound is prepared from intermediate 1 and the aforementioned alcohol following the procedures described in Example 10, 3 60 Megahertz (3 60 Megahertz, CDc130O.00 (911 s, Me3S!), 0.8 8 -0.93 (2Η, m, CH2), 2 63 (3 H, $

Me), 3.61-3 · 66 (2Η, m5 CH2), 5.92 (2H, s, CH2), 5.97 (2H, s, CH2), 6.89 (1H, s, Ar-H), 7.86 (1H

m, Ar-H), 8.02 (1H, t, J = 7.7Hz, A1H), 8.18 (1H, s, Ar-H), 8.23 (1H, d, J = 8.0Hz, Ar-H), 8.76 (1H d, J = 8.0Hz, Ar-H); MS (ES +) m / e 479 [MH] +. d) 3 -yl) -6-ΠΗ-1,2,3 -triazole 幷 -5_ Meishang, 4-triazole # 『3 · 4 · αΐΒ 耕 Gengze 逑 product, ethanol (10 ml) and 2N HC1 ( 20 ml) of the mixture was heated at 50 C for 15.2 for 5 hours. The solution was basified with saturated sodium carbonate solution to ρ Η 1 2 and the solvent was evaporated in 眞 2. The residue was azeotroped (X 2) with ethyl and alcohol and chromatographed on a silica gel. The residue was dissolved in 0-4% methanol / dichloromethane (gradient dissolution).

Generated the title product, 1H NMR (400 megahertz, CDC13) S -13- wood paper size returned __ ♦ installed — (read the precautions on the back before filling in this page) -ding, = mouthΦ 487710 A7 B7 Classics: ^ Central Sample ^-Bureau only 3 汸 ^, Heshan, printing system 5. Invention Description (11)

2.65 (3H, s, Me), 5.73 (2Η, s, CH2), 7.02 (1Η, s Ar-H), 1 7.87 (1H, t5 J = 7.8Hz, Ar-H), 7.99 -8.〇3 (2H m, 2 Ar-H), 8.24 (1H, d, J = 8.2HZ Ar H) 8.72 (1H, d, J = 7.9Hz, Ar-H); MS (ES +) m / e 349 [MH] +. Example 1 Methylisozazolmethyloxy, 1,2,4 _ 2 rabbits go to 丄 i, 4 _ a] g Tai Geng, 3 _ (5 azole di ^ 2 6- (2-methyl- 丄 ^ 1 ^ 唆 幷 -4-yl) methyl ^ £ ^ 1 ^ 4 and "3,4-a 1 phthalocyanine and 3 彳 5-methylisohumidazole-3 3 -triammonyl-1 _ ^ _ 4 -_ ag Taigen Under -31 C, nitrogen, drop hexamethyldisilazide (163 liters of a 1M solution in THF, ι63 mmol) into the solution prepared as in Reference Example 3 3- (5-methylisopurazol-3-yl) (1H-1,2,3-triazolidine-5-yl) methyloxy-1,2 in DMF (50 ml;) , 4-triazolo [3,4-a] phthalocyanine (2 4 1 mg, 0.6 2 6 mmol) was stirred in the solution, and the mixture was heated at -3 ° C for 1.5 hours, added dropwise Methyl iodide (0.1 ml, 6 mil) and the reaction mixture was warmed to room temperature overnight. Water was added and the solvent was evaporated in the air. The residue was distributed between dichloromethane and water. The aqueous phase was separated and re-extracted with dichloromethane (X1). The combined organic extracts were washed with brine (X0, dried (MgSCU) and evaporated in the air. The residue was chromatographed on a silica gel. 0-5% methanol / dichloro Alkane dissolution (gradient dissolution), followed by preparative HPLC (YMC Sil column, 250 X 20 mm) with 5% methanol / 1 _ zeolite: fe, the trisomer isomers were separated: ---- ^ -^-41 ^^ ------ 1T (Please read the notes on the back before filling out this page) ______ Wood paper scale IKEA standard -14- ((, NS) Λ4 size (210X 297) (Centi) 487710 A7 B7 Jingdi " Zhong Jue " This bureau only consumes β ^ Figure V. Description of the invention (12) Take small polar isomers (HPLC solvent system): 3-(5-ψ-isoisoxazole -3-yl 1: _6 -_ (1_1 _ ^ _ ^: 1,2,3-triazolidine-4-yl) methyloxy_1,2,4_tri ^ iLLUiiAlJiA 4 nmr (4〇o hundred 10,000 Hz, cdci3) s 2.59 (3Η, s, Me), 4.21 (3H, s, Me), 5.73 (2η, s, CH2), 6.89 (1Η, s, Ar-H), 7 · 79 (1Η, m, Ar_H), 7 · 9 4 (1 H, m, Ar-H), 8 · 1 0 (1 H, s, Ar-H), 8 · 2 2 (1 H d, J = 8.0Hz, Ar-H), 8.67 (1Η, d, J = 8.〇Hz, Ar-H); MS (ES +) m / e 3 6 3 [MH] + 0 intermediate polarity Isomers: 3- (5 · Methylisozaki Jun_3_ 棊 -method_j ^ 2,3 -tristetra-4-enyl) methyloxy-1,2,4 -trimethylol—幷 『3,4-a 1 酉Taikoujing 4 NMR (400 megahertz, CDC13) S 2.60 (3H, S, Me), 4.09 (3Η, s, Me), 5.78 (2Η, s, CH2), 6.90 (1H, d , J = 0.8Hz, Ar-H), 7.80 (1Η, m, Ar-H), 7.94 (1η, m, Ar-H), 8.25 (1Η, d, J = 8.0Hz, Ar-H), 8.65 (1H, d, J = 8.0 Hz, Ar-H), 8.73 (1Η, s5 Ar-H); MS (ES +) m / e 3 6 3 [MH] + 〇Max Polar isomers (HPLC solvent): 3-(5 diisocyanate _ 3 _ group _)-6_ (1-methyl-1,2,3 -triazolidine-5-yl) methyl Ioxy _ i, 2,4 -Sansheng 幷 "3,4-al g Taiken NMR (400 megahertz, CDC13) 5 2.56 (3H, s, Me), 4.19 (3 Η, s, Me), 5.76 (2h, s, CH2), 6.82 (1H, s, Ar-H), 7.80 (1H, m, Ar-H), 7.96 (1Η, m, Ar-H), 8.04 (1Η, s5) Ar-H), 8.12 (1H d, Bu 8.8Hz, Ar-H), 8.67 (1Η, d, J = 8: 0Hz, Ar-H); MS (ES +) m / e 3 63 [MH ] + o -15- IfUL degree of this paper is suitable for Chinese Valves in China. (cNS) M size (2l0x 297mm) I installed 丨 — (Please read the precautions on the back before filling this page) Order #

Claims (1)

Patent No. 87173320 Chinese Patent Application Amendment (June 90) 4 丨 莰 Announcement 487710 6. Scope of Patent Application—. · .R “------------- 1 · A 3- (5 -Shenyl X Purazol-3 -yl) -6- (1-Methyl-1,2,3-trisialyl-4-yl) methyloxy-1,2,4-mesatriazolo [3,4-a] phthalocyanine. 2. — used for A pharmaceutical composition for treating dementia and amnesia, comprising a compound according to item 1 of the patent application scope and a pharmaceutically acceptable carrier. 3. A compound according to item 1 of the patent application scope, which is used to manufacture a medicament for enhancing cognitive ability 4. A method for manufacturing a compound according to item 1 of the scope of patent application, which comprises a methylating agent such as lithium hexamethyldisilazide and 3_ (5_methylisoxazol-3-yltriazole _5_yl) methyloxy hydrazene [3,4 _a] is _ reacted in an organic solvent at a temperature of -40 ° C to 50 ° C and in an inert gas. (Please read the note on the back first Please fill in this page again) The paper printed by the Central Consumers' Association of the Ministry of Economic Affairs's Consumer Cooperatives applies the Chinese National Standard (CNS) A4 specification (210X 297 mm)