JPH0621073B2 - Central depressant - Google Patents
Central depressantInfo
- Publication number
- JPH0621073B2 JPH0621073B2 JP61049250A JP4925086A JPH0621073B2 JP H0621073 B2 JPH0621073 B2 JP H0621073B2 JP 61049250 A JP61049250 A JP 61049250A JP 4925086 A JP4925086 A JP 4925086A JP H0621073 B2 JPH0621073 B2 JP H0621073B2
- Authority
- JP
- Japan
- Prior art keywords
- uridine
- mmol
- central
- action
- sleep
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Description
【発明の詳細な説明】 〔産業上の利用分野〕 本発明は新規な医薬、更に詳細にはウリジン誘導体を含
有する中枢抑制剤に関する。DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a novel drug, and more particularly to a central inhibitor containing a uridine derivative.
近年、種々のストレスから睡眠持続障害、不眠症等の患
者が増加しつつあり、大きな社会問題となつている。そ
して、これらの疾患と中枢神経系の関係についての研究
が盛んに行なわれている。In recent years, the number of patients with sleep disorders, insomnia and the like has been increasing due to various stresses, which has become a major social problem. And research on the relationship between these diseases and the central nervous system is actively conducted.
最近、Y.Komodaら、K.Hondaら、およびS.Inoueらは、そ
れぞれ睡眠喪失ラツト脳幹から得られたウリジンが睡眠
促進物質の一つであることを報告した〔Biomed.Res.,
４，２２３（１９８３）；Neurosci.Res.,１，２４３
（1984）；Proc.Natl.Acad.Sci.U.S.A.,８１，６２４０
（１９８４）；Neuroscience Letters，４９，２０７
（１９８４）〕。また、WenzelおよびKeplingerは、ウ
ラシルがマウスのヘキソバルビタール睡眠時間を延長す
ることを報告している〔J.Am.Pharm.Assoc.４４，５６
（１９５５）；同４４，５５０（１９５５）〕。さら
に、Robertsはウリジンに抗けいれん作用があることを
報告している〔Brain Res.,５５，２９１（１９７
３）〕。Recently, Y. Komoda et al., K. Honda et al., And S. Inoue et al. Reported that uridine obtained from the sleep-deprived rat brain stem was one of the sleep promoting substances [Biomed. Res.
4 , 223 (1983); Neurosci.Res., 1 , 243.
(1984); Proc. Natl. Acad. Sci. USA, 81 , 6240.
(1984); Neuroscience Letters, 49 , 207.
(1984)]. Wenzel and Keplinger also reported that uracil prolongs hexobarbital sleep time in mice [J. Am. Pharm. Assoc. 44 , 56.
(1955); the 44, 550 (1955)]. Furthermore, Roberts reported that uridine has an anticonvulsant action [Brain Res., 55 , 291 (197).
3)].
しかしながら、これらの物質の作用は十分とはいえず、
優れた中枢抑制剤、特に睡眠促進剤の開発が望まれてい
た。However, the action of these substances is not sufficient,
It has been desired to develop excellent central depressants, especially sleep stimulants.
斯かる実情に鑑み、本発明者らは鋭意研究した結果、特
定のウリジン誘導体が優れた睡眠促進作用を有すること
を見い出し、本発明を完成した。In view of such circumstances, as a result of intensive studies, the present inventors have found that a specific uridine derivative has an excellent sleep promoting action, and completed the present invention.
すなわち、本発明は次の一般式(Ｉ) （式中、R1は水素原子、ハロゲン原子または低級アルキ
ル基を、R2は水素原子または低級アルキル基を、R3、R4
およびR5はそれぞれ水素原子または低級アルキル基を示
す） で表わされるウリジン誘導体を含有することを特徴とす
る中枢抑制剤を提供するものである。That is, the present invention has the following general formula (I) (In the formula, R 1 represents a hydrogen atom, a halogen atom or a lower alkyl group, R 2 represents a hydrogen atom or a lower alkyl group, R 3 , R 4
And R 5 each represent a hydrogen atom or a lower alkyl group), which is a uridine derivative.
本発明の中枢制剤の有効成分である一般式(Ｉ)のウリジ
ン誘導体は、例えば下記反応式に従つて製造される。The uridine derivative of the general formula (I), which is an active ingredient of the central control agent of the present invention, is produced, for example, according to the following reaction formula.
（式中、Ｘはハロゲン原子を示し、R1〜R5は前記と同
じ） すなわち、Ｎ−無置換ウリジン誘導体(II)に、ベンジル
ハライド誘導体(III)を反応させることにより、ウリジ
ン誘導体(Ｉ)が製造される。 (In the formula, X represents a halogen atom, and R 1 to R 5 are the same as above.) That is, by reacting the N-unsubstituted uridine derivative (II) with the benzyl halide derivative (III), the uridine derivative (I ) Is manufactured.
Ｎ−無置換ウリジン誘導体(II)としては、ウリジン、
２′，３′，５′−トリ−Ｏ−メチルウリジン、２′，
３′，５′−トリ−Ｏ−エチルウリジン、２′，３′，
５′−トリ−Ｏ−プロピルウリジン等が挙げられるが、
就中ウリジンまたは２′，３′，５′−トリ−Ｏ−メチ
ルウリジンが好ましい。Examples of the N-unsubstituted uridine derivative (II) include uridine,
2 ', 3', 5'-tri-O-methyluridine, 2 ',
3 ', 5'-tri-O-ethyluridine, 2', 3 ',
5'-tri-O-propyluridine and the like can be mentioned,
Uridine or 2 ', 3', 5'-tri-O-methyluridine is especially preferred.
ベンジルハライド誘導体(III)としては、ベンジルブロ
マイド、α−ブロム−ｏ−キシレン、α−ブロム−ｐ−
キシレン、ｏ−エチルベンジルブロマイド、ｏ−プロピ
ルベンジルブロマイド、ｐ−クロロベンジルブロマイ
ド、ｏ−クロロベンジルブロマイド、ｐ−ブロムベンジ
ルアイオダイド、α−フエニルエチルブロマイド等が挙
げられる。Examples of the benzyl halide derivative (III) include benzyl bromide, α-bromo-o-xylene, α-bromo-p-
Xylene, o-ethylbenzyl bromide, o-propylbenzyl bromide, p-chlorobenzyl bromide, o-chlorobenzyl bromide, p-bromobenzyl iodide, α-phenylethyl bromide and the like can be mentioned.
反応は、無水炭酸カリウム、無水炭酸ナトリウム等の塩
基の存在下、ジメチルホルムアミド（ＤＭＦ）、アセト
ン等の不活性溶媒中、５〜１５０℃の温度で１〜５０時
間行うことが好ましい。The reaction is preferably carried out in the presence of a base such as anhydrous potassium carbonate or anhydrous sodium carbonate in an inert solvent such as dimethylformamide (DMF) or acetone at a temperature of 5 to 150 ° C. for 1 to 50 hours.
斯くして得られたウリジン誘導体(Ｉ)の中枢抑制作用並
びに安全性について試験した結果を以下に示す。The results of a test for the central inhibitory action and safety of the uridine derivative (I) thus obtained are shown below.
＜中枢抑制作用＞ (1)脳室内投与による催眠作用 方法 １群２〜８匹のｄｄＮ系雄性マウス（体重２５±３ｇ）
を用い、脳室内（i.c.v.）に被検物質を３％ツイーン８
０生理食塩水に懸濁して投与した。そして、正向反射消
失からその回復までの時間（睡眠時間）を測定した。<Central depressant action> (1) Hypnotic action by intracerebroventricular administration Method 2 to 8 male ddN mice (body weight 25 ± 3 g)
3% Tween 8 in the ventricle (icv) of
It was suspended in 0 physiological saline for administration. Then, the time from the disappearance of the righting reflex to its recovery (sleeping time) was measured.
結果 結果を第１表、第１〜３図に示す。なお、化合物１〜４
は、後記実施例１〜４で得た化合物にそれぞれ対応す
る。Results The results are shown in Table 1 and FIGS. Compounds 1 to 4
Correspond to the compounds obtained in Examples 1 to 4 below, respectively.
第１表および第１〜３図より、ウリジン誘導体(Ｉ)は優
れた催眠作用を示すことがわかる。 From Table 1 and FIGS. 1 to 3, it can be seen that the uridine derivative (I) exhibits excellent hypnotic action.
(2)静脈内投与による催眠作用 方法 被検物質を静脈内投与する以外は、前記(1)の方法と同
様にして試験した。(2) Hypnotic Action by Intravenous Administration Method The test was conducted in the same manner as in the above (1) except that the test substance was administered intravenously.
結果 結果を第２表に示す。Results The results are shown in Table 2.
(3)ペントバルビタール睡眠に対する作用 方法 前記(1)と同様の動物を用いて行つた。被検物質を３％
ツイーン８０生理食塩水に懸濁して投与した。その１５
分後にペントバルビタールナトリウム４０mg／Kgを腹腔
内投与し、ペントバルビタール睡眠時間に与える影響を
検討した。 (3) Action on Pentobarbital Sleep Method The same animal as in (1) above was used. 3% test substance
It was suspended in Tween 80 physiological saline and administered. Part 15
After 40 minutes, pentobarbital sodium 40 mg / Kg was intraperitoneally administered to examine the effect on pentobarbital sleep time.
結果 結果を第３表に示す。Results The results are shown in Table 3.
第３表より、本発明のウリジン誘導体(Ｉ)は、睡眠促進
物質の一つとして知られているウリジン等よりも強力な
催眠効果を有する。 From Table 3, the uridine derivative (I) of the present invention has a stronger hypnotic effect than uridine which is known as one of sleep promoting substances.
＜急性毒性＞ 前記(1)と同様の動物を使用して、急性毒性試験をした
結果を第４表に示す。<Acute toxicity> Table 4 shows the results of an acute toxicity test using the same animals as in (1) above.
ウリジン誘導体(Ｉ)は、経口、非経口の何れの方法によ
つても投与することができ、本発明の中枢抑制剤は、こ
れに応じた各種剤型、例えば散剤、錠剤、カプセル剤、
顆粒剤、細粒剤等の経口投与用剤型；静脈注射剤、脳側
室内注射剤等の非経口投与用剤型とすることができる。 The uridine derivative (I) can be administered either orally or parenterally, and the central depressant of the present invention can be administered in various dosage forms such as powders, tablets, capsules,
Oral dosage forms such as granules and fine granules; parenteral dosage forms such as intravenous injections and intraventricular injections can be used.
上記製剤化は、自体公知の方法によつてなし得る。すな
わち、ウリジン誘導体(Ｉ)をデンプン、乳糖、マンニト
ール等の賦形剤；カルボキシメチルセルロースナトリウ
ム、ヒドロキシプロピルセルロース等の結合剤；結晶セ
ルロース、カルボキシメチルセルロースカルシウム等の
崩壊剤；タルク、ステアリン酸マグネシウム等の滑沢
剤；軽質無水ケイ酸等の流動性向上剤等を適宜組み合せ
て処方することにより散剤、錠剤、カプセル剤、顆粒剤
等を製造することができる。The above-mentioned formulation can be carried out by a method known per se. That is, the uridine derivative (I) is used as an excipient such as starch, lactose, and mannitol; a binder such as sodium carboxymethyl cellulose and hydroxypropyl cellulose; a disintegrant such as crystalline cellulose and carboxymethyl cellulose calcium; a lubricant such as talc and magnesium stearate. Lubricants: Powders, tablets, capsules, granules and the like can be produced by appropriately combining and formulating fluidity improvers such as light anhydrous silicic acid.
また、ウリジン誘導体(Ｉ)を注射剤とするには、生理食
塩水、水等の他に界面活性剤を利用して溶解あるいは懸
濁せしめることにより製造することができる。Further, the uridine derivative (I) can be prepared as an injection by dissolving or suspending it using a surfactant in addition to physiological saline, water and the like.
本発明の中枢抑制剤の投与量は、その疾患等により異な
るが、向精神、抗不安、抗てんかん、筋弛緩作用等を期
待する場合、成人に対しては、ウリジン誘導体(Ｉ)とし
て経口投与により１回当り２５〜５０mg／６０Kgが好ま
しい。また、睡眠持続障害や重症の不眠症患者に対して
は５０〜６０mg／６０Kgまで使用できる。更に、特殊な
精神科領域などにおいて強制的に睡眠を持続させる必要
がある場合には、脳側室内へ１．２〜２．０mg／Kg注入
することができる。The dose of the central depressant of the present invention varies depending on the disease and the like, but when antipsychotic, anxiolytic, antiepileptic, muscle relaxant action and the like are expected, it is orally administered to adults as a uridine derivative (I). Therefore, it is preferably 25 to 50 mg / 60 kg per dose. In addition, up to 50-60 mg / 60 kg can be used for patients with sleep disorders and severe insomnia. Furthermore, when it is necessary to forcibly maintain sleep in a special psychiatric region or the like, 1.2 to 2.0 mg / Kg can be injected into the cerebral side chamber.
本発明の中枢抑制剤は、優れた催眠作用を有し、睡眠持
続障害、不眠症等の他、種々の中枢興奮状態に起因する
疾患、例えば、不安、てんかん、筋緊張等の治療薬とし
て有用である。The central depressant of the present invention has an excellent hypnotic effect, and is useful as a therapeutic drug for sleep disorders, insomnia, and other diseases caused by various central excitatory states, such as anxiety, epilepsy, and muscle tone. Is.
次に実施例を挙げて本発明を説明する。 Next, the present invention will be described with reference to examples.
実施例１ N3−ベンジルウリジン（化合物１）： ウリジン４．３９５ｇ（１８mmol）と無水炭酸カリウム
４．２３３ｇ（３０．６mmol）を１２mlのジメチルホル
ムアミド（ＤＭＦ）と１２mlのアセトンに溶解し、臭化
ベンジル３．２１ml（２７mmol）を加え６０℃で６時間
撹拌した。反応液をＴＬＣで展開し、反応生成物を確認
した後、減圧蒸留にて溶媒を除去した。シリカゲル２０
０ｇを溶出溶媒（クロロホルム：メタノール＝９：１）
に懸濁させ、内径３．２cmのカラムに充てんし、カラム
クロマトグラフイーを行い、４．３２ｇの白色結晶を得
た。さらに水から再結晶し精製した。収量３．８３５
ｇ、収率６４％。生成物は機器分析によつて、N3−ベン
ジルウリジンであることを確認した。融点179.5〜1810
℃ 実施例２ N3−ｏ−キシリルウリジン（化合物２）： ウリジン９７７mg（４mmol）と無水炭酸カリウム９４０
mg（６．８mmol）を４mlのジメチルホルムアミドと４ml
のアセトンに溶解し、α−ブロム−ｏ−キシレン０．８
１ml（６．０mmol）を加え６０℃で２時間撹拌した。反
応液をTLCで展開し、反応生成物を確認した後、減圧蒸
留にて溶媒を除去した。Example 1 N 3 -benzyluridine (Compound 1): 4.395 g (18 mmol) of uridine and 4.233 g (30.6 mmol) of anhydrous potassium carbonate were dissolved in 12 ml of dimethylformamide (DMF) and 12 ml of acetone and brominated. 3.21 ml (27 mmol) of benzyl was added and the mixture was stirred at 60 ° C. for 6 hours. After the reaction solution was developed by TLC to confirm the reaction product, the solvent was removed by vacuum distillation. Silica gel 20
0 g of elution solvent (chloroform: methanol = 9: 1)
The mixture was suspended in a column, the column was filled with a column having an inner diameter of 3.2 cm, and column chromatography was performed to obtain 4.32 g of white crystals. Further, it was recrystallized from water and purified. Yield 3.835
g, 64% yield. The product was confirmed to be N 3 -benzyluridine by instrumental analysis. Melting point 179.5-1810
℃ EXAMPLE 2 N 3-o-xylyl uridine (Compound 2): uridine 977 mg (4 mmol) and anhydrous potassium carbonate 940
mg (6.8 mmol) with 4 ml of dimethylformamide and 4 ml
Dissolved in acetone to give α-bromo-o-xylene 0.8
1 ml (6.0 mmol) was added and the mixture was stirred at 60 ° C. for 2 hours. The reaction solution was developed by TLC, and after confirming the reaction product, the solvent was removed by distillation under reduced pressure.
シリカゲル１５０ｇをカラムに充てんし、溶出溶媒クロ
ロホルム：酢酸エチル：メタノール（５：４：１）を用
いてカラムクロマトグラフイーを行い１．０８ｇの白色
結晶を得た。さらにメタノール、水で再結晶化して精製
した。mp１６９．５−１７０．５℃収量８５８mg（６２
％）。機器分析データは下記に示す。The column was filled with 150 g of silica gel and subjected to column chromatography using an elution solvent of chloroform: ethyl acetate: methanol (5: 4: 1) to obtain 1.08 g of white crystals. Further, it was recrystallized with methanol and water for purification. mp 169.5-170.5 ° C Yield 858 mg (62
%). Instrumental analysis data is shown below.
元素分析（C17H20N2O6として） 1H-NMR（in DMSO-d6）δ： 2.28(3H,s,CH3),3.38-3.54(2H,m,5′-CH2-),3.60-3.96
(3H,m,2′-H,3′-H,4′-H),4.78(2H,s,-CH2-N),5.56-5.
64(2H,m,5-H,1′-H),6.48-7.00(4H,m,-C6H4),7.76(1H,
d,J＝8Hz,6-H)。Elemental analysis (as C 17 H 20 N 2 O 6 ) 1 H-NMR (in DMSO-d 6 ) δ: 2.28 (3H, s, CH 3 ), 3.38-3.54 (2H, m, 5′-CH 2- ), 3.60-3.96
(3H, m, 2′-H, 3′-H, 4′-H), 4.78 (2H, s, -CH 2 -N), 5.56-5.
64 (2H, m, 5-H, 1'-H), 6.48-7.00 (4H, m, -C 6 H 4 ), 7.76 (1H,
d, J = 8Hz, 6-H).
実施例３ N3−α−フエニルエチルウリジン（化合物３）： ウリジン１．４６５ｇ（６．０mmol）と無水炭酸カリウ
ム１．０８０ｇ（７．８mmol）をジメチルホルムアミド
１４mlに溶かしα−フエニルエチルブロマイド１．０８
０ml（７．８mmol）を加え８０℃で３６時間還流撹拌し
た。反応液をＴＬＣで展開し、反応生成物を確認した
後、減圧蒸留にて溶媒を除去した。Example 3 N 3 -α-phenylethyluridine (Compound 3): 1.465 g (6.0 mmol) of uridine and 1.080 g (7.8 mmol) of anhydrous potassium carbonate were dissolved in 14 ml of dimethylformamide to prepare α-phenylethyl bromide. 1.08
0 ml (7.8 mmol) was added and the mixture was stirred under reflux at 80 ° C. for 36 hours. After the reaction solution was developed by TLC to confirm the reaction product, the solvent was removed by vacuum distillation.
シリカゲル１５０ｇをカラムに充てんし、溶出溶媒クロ
ロホルム：酢酸エチル：メタノール（５：４：１）でカ
ラムクロマトグラフイーを行い、７０７mgの油状物質を
得た。少量のメタノールと酢酸エチルエステルと石油エ
ーテルの混合溶媒で再結晶化し、４６５mgの白色結晶を
精製した。mp１６０−１６３℃収量４６５mg（２２
％）。機器分析データは下記に示す。The column was filled with 150 g of silica gel and subjected to column chromatography with an eluting solvent chloroform: ethyl acetate: methanol (5: 4: 1) to obtain 707 mg of an oily substance. Recrystallization was performed with a small amount of a mixed solvent of methanol, ethyl acetate and petroleum ether, and 465 mg of white crystals were purified. mp 160-163 ° C Yield 465 mg (22
%). Instrumental analysis data is shown below.
元素分析（C17H20N2O6として） 1H-NMR(in DMSO-d6)δ： 1.70(3H,d,J＝6Hz,-CH3),3.38-3.58(2H,m,5′-CH2-),3.
62-3.96(3H,m,2′-H,3′-H,4′-H),5.44-5.60(2H,m,5-
H, 5.84-5.92(1H,d,J＝6Hz,1′-H),6.92-7.12(5H,m,-C
6H5),7.62-7.66(1H,d,J＝8Hz,6-H)。Elemental analysis (as C 17 H 20 N 2 O 6 ) 1 H-NMR (in DMSO-d 6 ) δ: 1.70 (3H, d, J = 6Hz, -CH 3 ), 3.38-3.58 (2H, m, 5′-CH 2- ), 3.
62-3.96 (3H, m, 2'-H, 3'-H, 4'-H), 5.44-5.60 (2H, m, 5-
H, 5.84-5.92 (1H, d, J = 6Hz, 1'-H), 6.92-7.12 (5H, m, -C
6 H 5 ), 7.62-7.66 (1H, d, J = 8Hz, 6-H).
実施例４ N3−ベンジル−２′，３′，５′−トリ−Ｏ−メチルウ
リジン（化合物４）： (i)シチジン４．８６ｇ（２０mmol）を１．５ＮＫＯＨ
２００mlに溶かし激しく撹拌した。次に１０Ｎ ＫＯＨ
１０mlを加えた後、直ちにジメチル硫酸５mlを加えた。
この操作を１５分間隔で１０回くり返し、さらに一晩撹
拌した。反応液をクロロホルム１００ml×１０で抽出し
エバポレートした。次に２．５ＭNaHSO3２５mlを加え、
さらに１００℃で５時間加熱した。反応液を室温に戻
し、１Ｎ ＮａＯＨ75mlを加え、さらに１５分後には１
Ｍ BaCl2７５mlを加えた。白濁した反応液をろ過し、
少量の水で洗つた。水層を塩酸で酸性にしてクロロホル
ム２００mlで抽出、芒硝を加え一晩放置しておいた。反
応液をエバポレートしたところ１．３４５ｇの油状物を
得た。1H−ＮＭＲで解析したところ、２′，３′，５′
−トリ−Ｏ−メチルウリジンであることが確認された。Example 4 N 3 - benzyl-2 ', 3', 5'-tri -O- methyluridine (Compound 4): (i) 1.5NKOH cytidine 4.86 g (20 mmol)
It was dissolved in 200 ml and stirred vigorously. Next, 10N KOH
Immediately after adding 10 ml, 5 ml of dimethyl sulfate was added.
This operation was repeated 10 times at intervals of 15 minutes and further stirred overnight. The reaction mixture was extracted with 100 ml of chloroform and evaporated. Then add 25 ml of 2.5M NaHSO 3
Furthermore, it heated at 100 degreeC for 5 hours. The reaction solution was returned to room temperature, 75 ml of 1N NaOH was added, and after 15 minutes, 1
75 ml of M BaCl 2 was added. The cloudy reaction solution is filtered,
It was washed with a small amount of water. The aqueous layer was acidified with hydrochloric acid and extracted with 200 ml of chloroform. Glauber's salt was added and the mixture was allowed to stand overnight. When the reaction solution was evaporated, 1.345 g of oily matter was obtained. When analyzed by 1 H-NMR, 2 ', 3', 5 '
-Tri-O-methyluridine was confirmed.
(ii) (i)で得た２′，３′，５′−トリ−Ｏ−メチルウ
リジン８１２mg（２．８mmol）と無水炭酸カリウム６５
８mg（４．８mmol）をアセトン８mlに溶かしベンジルブ
ロマイド０．５ml（４．２mmol）を加え、６０℃で７時
間還流撹拌し、冷後反応溶媒をエバポレートした。シリ
カゲル８０ｇを用いたカラムクロマトグラフイー（溶出
溶媒＝クロロホルム）より、９１２mgの油状物質を得
た。収率８５％。機器分析データは下記に示す。(ii) 812 mg (2.8 mmol) of 2 ', 3', 5'-tri-O-methyluridine obtained in (i) and anhydrous potassium carbonate 65
8 mg (4.8 mmol) was dissolved in 8 ml of acetone, 0.5 ml (4.2 mmol) of benzyl bromide was added, the mixture was stirred under reflux at 60 ° C. for 7 hours, and after cooling, the reaction solvent was evaporated. By column chromatography using 80 g of silica gel (eluting solvent = chloroform), 912 mg of an oily substance was obtained. Yield 85%. Instrumental analysis data is shown below.
ＩＲ（Liquid film）より、−ＯＨ（３６００cm-1）、
−CONH−（３２００cm-1）の吸収が消失していた。1 Ｈ−ＮＭＲ(ｉｎ ＣＤＣｌ3）δ： 3.10(3H,s,-O-CH3),3.16(3H,s,-O-CH3),3.32(3H,s,-O-C
H3),3.38-3.90(5H,m,5′-H2,2′-H,3′-H),4.70(2H,s,-
CH2-N),5.30(1H,d,J＝8Hz,5-H),5.50(1H,s,1′-H),6.64
-6.94(5H,m,-C6H5),7.30(1H,d,J＝8Hz,6-H)。From IR (Liquid film), -OH (3600 cm -1 ),
The absorption of -CONH- (3200 cm -1 ) had disappeared. 1 H-NMR (in CDCl 3 ) δ: 3.10 (3H, s, -O-CH 3 ), 3.16 (3H, s, -O-CH 3 ), 3.32 (3H, s, -OC
H 3 ), 3.38-3.90 (5H, m, 5′-H 2 , 2′-H, 3′-H), 4.70 (2H, s,-
CH 2 -N), 5.30 (1H, d, J = 8Hz, 5-H), 5.50 (1H, s, 1'-H), 6.64
-6.94 (5H, m, -C 6 H 5 ), 7.30 (1H, d, J = 8Hz, 6-H).
実施例５ ｐ−クロロベンジルブロマイドを用いて、実施例１と同
様の操作にて、N3−ｐ−クロロベンジルウリジンを得
た。Example 5 By using p-chlorobenzyl bromide and in the same manner as in Example 1, N 3 -p-chlorobenzyluridine was obtained.
第１〜３図は、化合物１〜３のマウス脳室内投与におけ
る催睡作用（睡眠時間）と投与量との関係をそれぞれ示
す図面である。1 to 3 are drawings showing the relationship between the hypnotic action (sleeping time) and the dose of Compounds 1 to 3 intracerebroventricular administration.
フロントページの続き (72)発明者 イン カン ホー アメリカ合衆国 39211 ミシシツピ，ジ ヤクソン，メドウ オークス ヒル パー ク デーアール 5050 (56)参考文献 特開 昭60−136515（ＪＰ，Ａ)Front Page Continuation (72) Inventor Inkan Ho United States 39211 Mississippi, Jackson, Meadow Oaks Hill Park D 5050 (56) References JP-A-60-136515 (JP, A)
Claims (2)
ル基を、R2は水素原子または低級アルキル基を、R3、R4
およびR5はそれぞれ水素原子または低級アルキル基を示
す） で表わされるウリジン誘導体を含有することを特徴とす
る中枢抑制剤。1. General formula (I) (In the formula, R 1 represents a hydrogen atom, a halogen atom or a lower alkyl group, R 2 represents a hydrogen atom or a lower alkyl group, R 3 , R 4
And R 5 each represent a hydrogen atom or a lower alkyl group).
許請求の範囲第１項記載の中枢抑制剤。2. The central depressant according to claim 1, wherein the main action of central depressant is a sleep promoting action.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61049250A JPH0621073B2 (en) | 1986-03-06 | 1986-03-06 | Central depressant |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61049250A JPH0621073B2 (en) | 1986-03-06 | 1986-03-06 | Central depressant |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62207218A JPS62207218A (en) | 1987-09-11 |
| JPH0621073B2 true JPH0621073B2 (en) | 1994-03-23 |
Family
ID=12825598
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61049250A Expired - Lifetime JPH0621073B2 (en) | 1986-03-06 | 1986-03-06 | Central depressant |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0621073B2 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2073464A1 (en) * | 1990-01-13 | 1991-07-14 | Masahiro Imaizumi | Anxiolytic drugs |
| CA2850367C (en) | 2011-09-30 | 2021-06-01 | Tufts University | Uridine diphosphate derivatives, compositions and methods for treating neurodegenerative disorders |
| JP6523958B2 (en) | 2012-09-28 | 2019-06-05 | タフツ・ユニバーシティ | Uridine diphosphate derivatives, prodrugs, compositions and their use |
| US10138265B2 (en) | 2013-03-13 | 2018-11-27 | Tufts University | Uridine nucleoside derivatives, compositions and methods of use |
| WO2014160502A1 (en) | 2013-03-13 | 2014-10-02 | Tufts University | Uridine nucleoside derivatives, compositions and methods of use |
-
1986
- 1986-03-06 JP JP61049250A patent/JPH0621073B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPS62207218A (en) | 1987-09-11 |
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