JPS60130572A - 5-(p-nitrophenyl)tetrazole derivative - Google Patents

5-(p-nitrophenyl)tetrazole derivative

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Publication number
JPS60130572A
JPS60130572A JP23724783A JP23724783A JPS60130572A JP S60130572 A JPS60130572 A JP S60130572A JP 23724783 A JP23724783 A JP 23724783A JP 23724783 A JP23724783 A JP 23724783A JP S60130572 A JPS60130572 A JP S60130572A
Authority
JP
Japan
Prior art keywords
nitrophenyl
solvent
compound
tetrazole
formula
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.)
Pending
Application number
JP23724783A
Other languages
Japanese (ja)
Inventor
Eiichi Kano
加納 永一
Masayo Furukawa
古川 雅代
Yoshito Nozaki
義人 野崎
Takashi Harimoto
孝史 播本
Masataka Fukumura
福村 正孝
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sumitomo Chemical Co Ltd
Original Assignee
Sumitomo Chemical Co Ltd
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Filing date
Publication date
Application filed by Sumitomo Chemical Co Ltd filed Critical Sumitomo Chemical Co Ltd
Priority to JP23724783A priority Critical patent/JPS60130572A/en
Publication of JPS60130572A publication Critical patent/JPS60130572A/en
Pending legal-status Critical Current

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Abstract

NEW MATERIAL:The 5-(p-nitrophenyl)tetrazole derivative of formula (R is lower alkyl substituted with a substituent group selected from carboxyl, hydroxyl and lower alkoxy). EXAMPLE:2-[5-(p-Nitrophenyl)tetrazol-2-yl]acetic acid. USE:It has strong radiation sensitizing effect and is useful as a drug. It has no side effect such as central toxicity. PREPARATION:The compound of formula can be produced by reacting the compound of formula RX (X is halogen or its equivalent reactive group) with 5-(p- nitrophenyl)tetrazole in a solvent such as methanol in the presence of an acid acceptor base. The base is e.g. sodium hydroxide, and the reaction is carried out under ice-cooling - at the boiling point of the solvent.

Description

【発明の詳細な説明】 本発明は新規な5−(p−ニトロフェニル)テトラゾー
ル誘導体に関する。
DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel 5-(p-nitrophenyl)tetrazole derivatives.

本発明の新規な5−(p−二トロフェニル)テトラゾー
ル誘導体は一般式(I) 凡 〔式中孔1は、カルボキシ、ヒドロキシおよび低級アル
コキシ基から選ばれる置換基で置換された低級アルキル
基を意味する。〕 で表わされる。
The novel 5-(p-nitrophenyl)tetrazole derivatives of the present invention are represented by the general formula (I) [Formula hole 1 is a lower alkyl group substituted with a substituent selected from carboxy, hydroxy and lower alkoxy groups] means. ] It is expressed as .

ここで、低級アルコキシ基まtごは置換された低級アル
キル基におけるアルキル基部分としては、例えばメチル
、エチル、n−プロピル、イソプロピル、n−ブチルな
どの炭gei〜4のアルキル基をあげることができる。
Here, examples of the alkyl group moiety in the lower alkyl group substituted with a lower alkoxy group include alkyl groups having a carbon atom such as methyl, ethyl, n-propyl, isopropyl, and n-butyl. can.

置換された低級アルキル基とは、−置換もしくは二置換
であるかまたはそれ以上の置換基を有してもよく、多置
換である場合にはその置換基は同種または異種であり得
ろう また、aで示される基がカルボキシル基を有する場合に
は、本発明化合物は、その塩を包含する。
The substituted lower alkyl group may be -substituted or disubstituted, or may have more substituents, and in the case of polysubstitution, the substituents may be the same or different. When the group represented by a has a carboxyl group, the compounds of the present invention include salts thereof.

一般に、低酸素環境下にある腫瘍細胞は、同細胞が正酸
素(好気的)環境下にある場合に比して放射線感受性が
低下する。腫瘤型腫瘍がある程度の腫瘤径に達すると、
その中心部はいわゆる中心壊死に陥り、腫瘤の最外縁部
は酸素分圧と栄養補給が血行により良好に保たれ、腫瘍
細胞は旺盛に増殖している。中心部と最外縁部との中間
部には低酸素下に生存している細胞がある。斯かる中間
部細胞は低酸素環境下にあるため、最外縁部細胞に比べ
て放射線抵抗性であり、従って放射線治療後腫瘍再発の
原因となるので、この中間部低酸素腫瘍細胞の放射線感
受性を増強することが強く望まれている。
In general, tumor cells in a hypoxic environment are less sensitive to radiation than when the same cells are in a normoxic (aerobic) environment. When a mass-type tumor reaches a certain diameter,
The center of the tumor has fallen into so-called central necrosis, and the outermost edge of the tumor has good oxygen partial pressure and nutritional support due to blood circulation, and tumor cells are actively proliferating. In the middle between the center and the outermost edge there are cells that survive under hypoxia. Because these intermediate cells are under a hypoxic environment, they are more radioresistant than the outermost cells, and therefore cause tumor recurrence after radiotherapy. There is a strong desire to strengthen this.

このような作用を有する代表的な薬剤として、ミソニダ
ゾールのような2−ニトロイミダゾール誘導体が知らレ
テイる( J、O,Asquith 。
2-nitroimidazole derivatives such as misonidazole are known as representative drugs having such effects (J. O. Asquith).

M、Watts 、 etal、 Rodiat、 R
es、、 60 、108−118 (1974))が
、現在のところその放射線増感効果は充分なものとはい
えない。
M., Watts, etal., Rodiat, R.
es, 60, 108-118 (1974)), but at present its radiosensitizing effect cannot be said to be sufficient.

本発明によって得られる化合物は強い放射線増感作用を
有し、又、ニトロイミダゾール誘導体の持つ中枢毒性等
の副作用の低減が期待される。
The compound obtained by the present invention has a strong radiosensitizing effect, and is also expected to reduce side effects such as central toxicity of nitroimidazole derivatives.

一般式(I)で表わされる化合物は一般式(n)RX 
(ml 〔式中Rは前記に同じであり、Xはハロゲン原子猿たは
その反応性均等基を意味する。〕で表わされる化合物を
5−(p−二トロフェニル)テトラソール(m)と反応
させることにより合成される。
The compound represented by the general formula (I) has the general formula (n)RX
(ml [In the formula, R is the same as above, and X means a halogen atom or a reactive equivalent group thereof.] 5-(p-nitrophenyl)tetrasol (m) Synthesized by reaction.

ここでいうハロゲン原子とは例えば塩素原子、臭素原子
などであり、また反応性均等基とはこれらの置換基と同
じ反応性を示すものを言い、例エバメタンスルホニルオ
キシ&、p7トルエンスルホニルオキシ基等である。
The halogen atom here is, for example, a chlorine atom, a bromine atom, etc., and the reactive equivalent group is one that shows the same reactivity as these substituents, such as evamethanesulfonyloxy &, p7 toluenesulfonyloxy group. etc.

出発原料となる化合物(劃は文献公知の化合物であり、
p−ニトロベンゾニトリルとアジドとの反応によって合
成することができる(W、G。
The starting material is a compound known in the literature.
It can be synthesized by the reaction of p-nitrobenzonitrile and azide (W, G).

Finnegan、R,A、 Henry and R
,Lofquist、 J、Am。
Finnegan, R.A., Henry and R.
, Lofquist, J. Am.

Ohem、soc、、 80 、8908 、 (19
58))。
Ohem, soc,, 80, 8908, (19
58)).

化合物(nI)と化合物(rl)との反応は一般に溶媒
中、脱酸剤塩基の存在下に行なわれる。この様な溶媒と
してはメタノール、エタノール、イソプロパツール等の
アルコール溶媒、ジメチルホルムアミド等の非プロトン
性極性溶媒、テトラヒドロフラン、ジオキサン等のエー
テル系溶媒が挙げられる。又、本反応に用いられる塩基
としては水酸化ナトリウム、水酸化カリウム、無水炭酸
ナトリウム、無水炭酸カリウムのような無機塩基、又は
トリエチルアミン、N−メチルモルホリン、ピリジンの
ような有機塩基が挙げられる。反応温度は特に限定され
るものではないが、一般に水冷下乃至溶媒の沸点下に行
なわれる。
The reaction between compound (nI) and compound (rl) is generally carried out in a solvent in the presence of a deoxidizing base. Examples of such solvents include alcohol solvents such as methanol, ethanol and isopropanol, aprotic polar solvents such as dimethylformamide, and ether solvents such as tetrahydrofuran and dioxane. Examples of the base used in this reaction include inorganic bases such as sodium hydroxide, potassium hydroxide, anhydrous sodium carbonate, and anhydrous potassium carbonate, and organic bases such as triethylamine, N-methylmorpholine, and pyridine. Although the reaction temperature is not particularly limited, it is generally carried out under water cooling or below the boiling point of the solvent.

一般式(I)に於て、Bで示される基が窒素原子のβ位
にヒドロキシ基を有する基である本発明化合物を製造す
る場合には、原料化合物として相当するエポキシ誘導体
を用いて化合物(m)と反応させることによっても合成
することがでなわれる。この様な溶媒としてはメタノー
ル、エタノール、イソプロパツール等のアルコール溶媒
、ジメチルホルムアミド等の非プロトン性極性溶媒、ク
ロロホルム、ジクロルメタン等のハロゲン化炭化水素溶
媒、テトラヒドロフラン、ジオキサン等のエーテル系溶
媒が挙げられる。
In general formula (I), when producing the compound of the present invention in which the group represented by B is a group having a hydroxy group at the β-position of the nitrogen atom, the compound ( It can also be synthesized by reacting with m). Examples of such solvents include alcohol solvents such as methanol, ethanol, and isopropanol, aprotic polar solvents such as dimethylformamide, halogenated hydrocarbon solvents such as chloroform and dichloromethane, and ether solvents such as tetrahydrofuran and dioxane. .

又、本反応に用いられる塩基としては水酸化ナトリウム
、水酸化カリウム、無水炭酸ナトリウム、無水炭酸カリ
ウムのような無機塩基、又はトリエチルアミン、N−メ
チルモルホリン、ピリジンのような有機塩基が挙げられ
る。反応温度は特lこ限定されるものではないが、一般
に水冷下乃至溶媒の沸点下に行なわれる。
Examples of the base used in this reaction include inorganic bases such as sodium hydroxide, potassium hydroxide, anhydrous sodium carbonate, and anhydrous potassium carbonate, and organic bases such as triethylamine, N-methylmorpholine, and pyridine. Although the reaction temperature is not particularly limited, it is generally carried out under water cooling or below the boiling point of the solvent.

一般式(1)に於て凡て示される基が窒素原子のβ位お
よびγ位にヒドロキシ基を有する基である本発明化合物
を製造する場合には、化合物(m)とエビハロヒドリ誘
導体から構成される装置化合物(I)とエビハロヒドリ
ン誘導体との反応は一般に溶媒中、塩基の存在下に行わ
れ、溶媒としてはメタノール、エタノール、イソプロパ
ツール等のアルコール溶媒、ジメチルポルムアミド等の
非プロトン性極性溶媒、テトラヒドロフラン、ジオキサ
ン等のエーテル系溶媒が挙げられる。
When producing the compound of the present invention in which all the groups shown in general formula (1) are groups having hydroxy groups at the β and γ positions of the nitrogen atom, the compound consisting of the compound (m) and the shrimp halohydride derivative The reaction between compound (I) and the shrimp halohydrin derivative is generally carried out in a solvent in the presence of a base, and the solvent may be an alcoholic solvent such as methanol, ethanol, isopropanol, or an aprotic polar solvent such as dimethylpolamide. , tetrahydrofuran, dioxane, and other ether solvents.

又、本反応に用いられる塩基としては無水炭酸ナトリウ
ム、無水炭酸カリウムのような無機塩基、又はトリエチ
ルアミン、N−メチルモルホリンのような有機塩基が挙
げられる。反応温度は特に限定されるものではないが一
般に水冷下乃至溶媒の沸点下に行われる。
Examples of the base used in this reaction include inorganic bases such as anhydrous sodium carbonate and anhydrous potassium carbonate, and organic bases such as triethylamine and N-methylmorpholine. Although the reaction temperature is not particularly limited, it is generally carried out under water cooling or below the boiling point of the solvent.

また、1.2−エポキシ−8−(5−(p−ニトロフェ
ニル)テトラゾリル)プロパン誘導体の開環反応は一般
に溶媒中、酸触媒存在下で加水分解をすることにより行
われる。
Further, the ring-opening reaction of the 1,2-epoxy-8-(5-(p-nitrophenyl)tetrazolyl)propane derivative is generally carried out by hydrolysis in a solvent in the presence of an acid catalyst.

このような溶媒としては水あるいは水と有機溶媒との混
合溶媒が用いられ、有機溶媒としては例えばメタノール
、エタノール等のアルコール溶媒、ジメチルホルムアミ
ド、ジメチルスルホキシド等の非プロトン性極性溶媒、
アセトンなどが挙げられる。
As such a solvent, water or a mixed solvent of water and an organic solvent is used, and examples of the organic solvent include alcohol solvents such as methanol and ethanol, aprotic polar solvents such as dimethylformamide and dimethyl sulfoxide,
Examples include acetone.

また酸触媒としては塩酸、硫酸等の無機酸、トリフルオ
ロ酢酸、トリニトロベンゼンスルホン酸等の有機酸が挙
げられる。
Examples of acid catalysts include inorganic acids such as hydrochloric acid and sulfuric acid, and organic acids such as trifluoroacetic acid and trinitrobenzenesulfonic acid.

反応温度は特に限定されるものではないが一般に、水冷
下乃至溶媒の沸点下に行われる。
Although the reaction temperature is not particularly limited, it is generally carried out under water cooling or below the boiling point of the solvent.

一般式(f)で表わされる5−(p−ニトロフェニル)
テトラゾール誘導体には置換基孔がテトラゾール環の1
位に結合した化合物と2位に結合した化合物が存在する
。本発明は、これら2つの位置異性体を包含するが、カ
ラムクロマトグラフィー、再結晶などの方法により必要
に応じて2つの異性体を分離することができる。
5-(p-nitrophenyl) represented by general formula (f)
In the tetrazole derivative, the substituent hole is located at one of the tetrazole rings.
There are compounds bonded to the 2-position and compounds bonded to the 2-position. Although the present invention includes these two positional isomers, the two isomers can be separated as necessary by methods such as column chromatography and recrystallization.

さらに、一般式(1)において几で示される基がカルボ
キシル基を有する場合には、必要に応じて当該化合物を
塩として取得することができる。そのような塩としては
、例えばナトリウム、カリウム、カルシウム、マグネシ
ウム塩などの無機塩基との塩および医薬として許容し得
るアミン類との塩などをあげることができる。
Furthermore, when the group represented by 几 in general formula (1) has a carboxyl group, the compound can be obtained as a salt if necessary. Examples of such salts include salts with inorganic bases such as sodium, potassium, calcium, and magnesium salts, and salts with pharmaceutically acceptable amines.

本発明によって提供される化合−は、経口又は非経口投
与に適した有機又は無機の不活性な担体物質並びに補助
物質と混合して、固体又は液体の形で投与することがで
きるう本発明化合物の増感剤としての投与凰は、用法、
患者の年令、性別その他の条件、疾患の程度により適宜
選択されるが、通常有効成分の量は1日当たり、体重1
Kg当たり約0.1〜100qとするのが良い。
The compounds provided by the present invention can be administered in solid or liquid form in admixture with organic or inorganic inert carrier substances and auxiliary substances suitable for oral or parenteral administration. Administration as a sensitizer, usage,
Although the amount of the active ingredient is selected as appropriate depending on the patient's age, gender and other conditions, and the severity of the disease, the amount of the active ingredient is usually given per body weight per day.
It is good to set it as about 0.1-100q per kg.

以下の実施例は本発明により提供される化合物の製造法
を例示するものである。
The following examples illustrate methods for making the compounds provided by this invention.

〔実施例1) 2−〔5−(P−ニトロフェニル)テト
ラゾール−2−イル〕 酢酸およびそのナトリウム塩 5−(p−ニトロフェニル)テトラゾール5.7011
をエタノール100 ml に溶解させ、水酸化カリウ
ム1.68Fとエチル 2−ブロモアセテート8−88
 mL を加えて、15時間加熱還流し1こ。室温に戻
した後、反応液より溶媒を減圧留去し、残渣をクロロホ
ルムを溶出液とするシリカゲルカラムクロマトグラフィ
ーにより分離、精製し、エチル 2−〔5−(p−ニド
拍フェニル)テトラゾール−2−イル〕アセテート8.
829を得た。
[Example 1] 2-[5-(P-nitrophenyl)tetrazol-2-yl] Acetic acid and its sodium salt 5-(p-nitrophenyl)tetrazole 5.7011
was dissolved in 100 ml of ethanol, potassium hydroxide 1.68F and ethyl 2-bromoacetate 8-88
Add 1 mL of the mixture and heat under reflux for 15 hours. After returning to room temperature, the solvent was distilled off from the reaction solution under reduced pressure, and the residue was separated and purified by silica gel column chromatography using chloroform as an eluent. -yl] acetate 8.
I got 829.

融点104〜105℃ NMR(ODOzs) δ(p、p、m、)曾 1.81(8H1L(J=7Hz )) 、4.27(
2B、+(J=7’Hz ) )5.49(2H,s)
 8.82(4H,s)このようにして得られたエチル
 2−〔5−(p−ニトロフェニル)テトラゾール−2
−イル〕アセテ−1−1,88Nをメタノール80 m
A に溶解させ、水酸化ナトリウム0.241を加えて
40〜50°Cで1時間攪拌した。
Melting point 104-105℃ NMR (ODOzs) δ (p, p, m,) 1.81 (8H1L (J = 7Hz)), 4.27 (
2B, +(J=7'Hz) )5.49(2H,s)
8.82 (4H,s) Ethyl 2-[5-(p-nitrophenyl)tetrazole-2 thus obtained
-yl] acetate-1-1,88N in methanol 80 m
The mixture was dissolved in A and 0.241 of sodium hydroxide was added, and the mixture was stirred at 40 to 50°C for 1 hour.

析出した結晶を戸数、乾燥して、掲題化合物を1.01
g得た。
The precipitated crystals were dried several times, and the title compound was 1.01%
I got g.

融点297°〜308℃ このものを蒸留水に溶解させ濃塩酸でpH1〜2とした
後、析出した結晶を枦取、乾燥することにより、2−(
5−(p−ニトロフェニル)テトラゾール−2−イル〕
酢酸をo、sog得た。
Melting point: 297° to 308°C After dissolving this in distilled water and adjusting the pH to 1 to 2 with concentrated hydrochloric acid, the precipitated crystals were collected and dried to obtain 2-(
5-(p-nitrophenyl)tetrazol-2-yl]
O, sog of acetic acid was obtained.

融点187〜iss℃ NMR(d6−DM80)δ(p、p、m、)6.78
(2H,s) 8.84(4H1s)〔実施例21 a
−〔5−(p−二トロフェニル)テトラゾール−2−イ
ル〕 −1−メトキシプロパノ−2− オール 5−(p−ニトロフェニル)テトラゾール8.82f/
をエタノール50 mL に溶解させ、無水炭酸カリウ
ム0.281と、1.2−エポキシ−3−メトキシプロ
パン2.61fを加え、2時間加熱還流した。室温に戻
した後、不溶物を枦去、溶媒を減圧留去し、残渣をクロ
ロホルム−メタノール(98/2=v/V)を溶出液と
するシリカゲルカラムクロマトグラフィーにより精製し
て掲題化合物2.’15f/を得た。
Melting point 187~iss°C NMR (d6-DM80) δ (p, p, m,) 6.78
(2H,s) 8.84 (4H1s) [Example 21 a
-[5-(p-nitrophenyl)tetrazol-2-yl] -1-methoxypropanol-2-ol 5-(p-nitrophenyl)tetrazole 8.82f/
was dissolved in 50 mL of ethanol, 0.281 g of anhydrous potassium carbonate and 2.61 f of 1,2-epoxy-3-methoxypropane were added, and the mixture was heated under reflux for 2 hours. After returning the temperature to room temperature, insoluble matter was removed, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography using chloroform-methanol (98/2=v/V) as an eluent to obtain the title compound 2. 'I got 15f/.

融点80〜81℃ NMR(ODOza) J(p、1)、m、)8、47
(8H,s)、8.57(2H,d(J=5Hz))。
Melting point 80-81°C NMR (ODOza) J (p, 1), m, ) 8, 47
(8H, s), 8.57 (2H, d (J=5Hz)).

4、21〜4.77(LH、m ) 。4, 21-4.77 (LH, m).

4、86 (2H,d(J=5Hz)) 、 8.81
(4H,s)〔実施例8)2−〔5−(p−二トロフェ
ニル)テトラゾール−2−イル〕 エタノール 5−(p−ニトロフェニル)テトラゾール0、951を
エタノール15 ml に溶解させ、水酸化カリウム0
.28 IIを加えて1時間加熱還流後、2−ブロモエ
タノール0.854 m4を滴下し更に9時間加熱還流
した。室温に戻した後、不溶物を沖去、溶媒を減圧留去
し、98− 残渣ヲクロロホルムーメタノ ル(/2−v/V)を溶
出液とするシリカゲルカラムクロマトグラフィーにより
精製して1局題化合物0、84 IIを得たう 融点125〜126°C NMR(d6−DM80) J(P −P −m、 )
8.85〜4.15(2H,m)。
4,86 (2H, d(J=5Hz)), 8.81
(4H,s) [Example 8] 2-[5-(p-nitrophenyl)tetrazol-2-yl] Ethanol 5-(p-nitrophenyl)tetrazole 0.951 was dissolved in 15 ml of ethanol, and water Potassium oxide 0
.. After adding 28 II and heating under reflux for 1 hour, 0.854 m4 of 2-bromoethanol was added dropwise and the mixture was further heated under reflux for 9 hours. After returning to room temperature, insoluble materials were removed, the solvent was distilled off under reduced pressure, and the 98-residue was purified by silica gel column chromatography using chloroform-methanol (/2-v/V) as an eluent. The title compound 0,84 II was obtained, melting point 125-126°C NMR (d6-DM80) J(P-P-m, )
8.85-4.15 (2H, m).

4.56〜4.91(2H,m)。4.56-4.91 (2H, m).

5.69(1H,s )、8.80(4H,8)〔実施
例41 8−〔5’−(P−テトロフェニル)テトラゾ
ール−2−イル〕 プロパン−1−オール 5−(p−ニトロフェニル)テトラゾール8.809を
エタノール50 mL に溶解させ水酸化カリウム1.
45Nを加えて75°Cまで加熱後、8−クロロプロパ
ツール2.2’7fおよびヨウ化ナトリウム8.61を
加え26時間同温度で攪拌した。室温に戻した後不溶物
を枦去、溶媒を減圧留去し残渣をクロロホルム−メタノ
ール(98/2=V/v)を溶出液とするシリカゲルカ
ラムクロマトグラフィーにより精製して掲題化合物1.
65Fを得た。
5.69 (1H,s), 8.80 (4H,8) [Example 41 8-[5'-(P-tetrophenyl)tetrazol-2-yl] Propan-1-ol 5-(p-nitro Dissolve 8.809 phenyl)tetrazole in 50 mL of ethanol and add 1.809 g of potassium hydroxide.
After adding 45N and heating to 75°C, 2.2'7f of 8-chloropropanol and 8.61ml of sodium iodide were added and stirred at the same temperature for 26 hours. After returning the temperature to room temperature, insoluble matter was removed, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography using chloroform-methanol (98/2=V/v) as an eluent to obtain the title compound 1.
Obtained 65F.

融点77.5〜78.5℃ NMR(d6−DM80) a(1)、Il、m、)1
.98〜2.42 (2H、m ) 8.52 (2H、t (J=6H7,))4.05(
1H,11) 4.79 (2ff 、 t (J=7.5H7) )
8.25(4H,s ) 〔実施例5’) −8−15−(1)−二トロフェニル
)テトラゾール−2−イル) プロパン−1,2−ジオール 5−(p−二トロフェニル)テトラゾール8.0f、無
水炭酸カリウム180qをエピクロルヒドリン60 m
l、 に加えて80分間加熱還流1ノだ。室温に戻した
後不溶物を枦去、溶媒を減圧留去し残渣をクロロホルム
−メタノール(98/2=V/v)を溶出液とするシリ
カゲルカラムクロマトグラフィーにより精製して1.2
−エポキシ−8−(5−(p−二トロフェニル)テトラ
ゾール−2−イル)プロパン 2.2gを得た。
Melting point 77.5-78.5°C NMR (d6-DM80) a(1), Il, m, )1
.. 98~2.42 (2H, m) 8.52 (2H, t (J=6H7,)) 4.05 (
1H, 11) 4.79 (2ff, t (J=7.5H7))
8.25(4H,s) [Example 5') -8-15-(1)-nitrophenyl)tetrazol-2-yl) propane-1,2-diol 5-(p-nitrophenyl)tetrazole 8.0f, 180q of anhydrous potassium carbonate and 60 m of epichlorohydrin
1, and then heat under reflux for 80 minutes. After returning to room temperature, insoluble matter was removed, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography using chloroform-methanol (98/2 = V/v) as an eluent.
-Epoxy-8-(5-(p-nitrophenyl)tetrazol-2-yl)propane 2.2g was obtained.

このようにして得られた1、2−エポキシ−8−(5−
(p−二トロフェニル)テトラゾール−2−イルンプロ
パン246岬に6規定価酸10 ml を加え60〜6
5℃にて8時間攪拌した。氷冷した後アンモニア水にテ
中和後酢酸エチルにて抽出し、溶媒を減圧留去し残渣を
クロロホルム−メタノール(9515)を溶出液とする
シリカゲルカラムクロマトグラフィーにより精製して掲
題化合物129岬を得た。
The 1,2-epoxy-8-(5-
Add 10 ml of 6N acid to 246 capes of (p-nitrophenyl)tetrazol-2-yrunpropane and mix 60-6
The mixture was stirred at 5°C for 8 hours. After cooling on ice, the mixture was neutralized with aqueous ammonia, extracted with ethyl acetate, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography using chloroform-methanol (9515) as an eluent to obtain the title compound 129 Misaki. Obtained.

融点108〜109℃ NMR(d6−DMSO) J(p、p、+n、)18
7〜8.57 (2H,ml) 3.98〜4.25(1H,m)
Melting point 108-109°C NMR (d6-DMSO) J (p, p, +n,) 18
7-8.57 (2H, ml) 3.98-4.25 (1H, m)

Claims (1)

【特許請求の範囲】 一般式 〔式中孔は、カルボキシ、ヒドロキシおよび低級アルコ
キシ基から選ばれる置換基で置換された低級アルキル基
を表わす。〕 で示される5−(p−ニトロフェニル)テトラゾール誘
導体。
[Claims] General formula [The middle hole in the formula represents a lower alkyl group substituted with a substituent selected from carboxy, hydroxy and lower alkoxy groups. ] A 5-(p-nitrophenyl)tetrazole derivative represented by the following.
JP23724783A 1983-12-15 1983-12-15 5-(p-nitrophenyl)tetrazole derivative Pending JPS60130572A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP23724783A JPS60130572A (en) 1983-12-15 1983-12-15 5-(p-nitrophenyl)tetrazole derivative

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP23724783A JPS60130572A (en) 1983-12-15 1983-12-15 5-(p-nitrophenyl)tetrazole derivative

Publications (1)

Publication Number Publication Date
JPS60130572A true JPS60130572A (en) 1985-07-12

Family

ID=17012576

Family Applications (1)

Application Number Title Priority Date Filing Date
JP23724783A Pending JPS60130572A (en) 1983-12-15 1983-12-15 5-(p-nitrophenyl)tetrazole derivative

Country Status (1)

Country Link
JP (1) JPS60130572A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994013675A1 (en) * 1992-12-14 1994-06-23 Yamanouchi Pharmaceutical Co., Ltd. Novel process for producing pyrazolotriazole derivative

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS4898029A (en) * 1972-02-28 1973-12-13
US3790588A (en) * 1969-10-24 1974-02-05 Gulf Research Development Co Method of manufacturing dialkylamino-1,3,4-oxadiazoles and 1,3,4-thiadiazoles
US3865570A (en) * 1972-02-28 1975-02-11 Ici Ltd Plant growth stunting process
JPS57159711A (en) * 1981-03-28 1982-10-01 Oorudo Kiiheizu:Kk Low oxygen cell sensitizer for radiation
JPS57206021A (en) * 1981-05-04 1982-12-17 Optical Coating Laboratory Inc Method and device for forming and utilizing active molecular beam

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3790588A (en) * 1969-10-24 1974-02-05 Gulf Research Development Co Method of manufacturing dialkylamino-1,3,4-oxadiazoles and 1,3,4-thiadiazoles
JPS4898029A (en) * 1972-02-28 1973-12-13
US3865570A (en) * 1972-02-28 1975-02-11 Ici Ltd Plant growth stunting process
JPS57159711A (en) * 1981-03-28 1982-10-01 Oorudo Kiiheizu:Kk Low oxygen cell sensitizer for radiation
JPS57206021A (en) * 1981-05-04 1982-12-17 Optical Coating Laboratory Inc Method and device for forming and utilizing active molecular beam

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994013675A1 (en) * 1992-12-14 1994-06-23 Yamanouchi Pharmaceutical Co., Ltd. Novel process for producing pyrazolotriazole derivative

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