JPS6115059B2 - - Google Patents
Info
- Publication number
- JPS6115059B2 JPS6115059B2 JP8527977A JP8527977A JPS6115059B2 JP S6115059 B2 JPS6115059 B2 JP S6115059B2 JP 8527977 A JP8527977 A JP 8527977A JP 8527977 A JP8527977 A JP 8527977A JP S6115059 B2 JPS6115059 B2 JP S6115059B2
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- butenyloxy
- acetone
- ethanol
- group
- 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.)
- Expired
Links
- -1 3-methyl-2-butenyloxy group Chemical group 0.000 claims description 32
- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 claims description 15
- 235000005513 chalcones Nutrition 0.000 claims description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 47
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 46
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 40
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- 239000000203 mixture Substances 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 230000002378 acidificating effect Effects 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- 239000002904 solvent Substances 0.000 description 11
- 238000003756 stirring Methods 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- SULYEHHGGXARJS-UHFFFAOYSA-N 2',4'-dihydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1O SULYEHHGGXARJS-UHFFFAOYSA-N 0.000 description 4
- MXMQIRYBCYFUOK-UHFFFAOYSA-N 2-(3-methylbut-2-enoxy)-1-phenylethanone Chemical compound CC(C)=CCOCC(=O)C1=CC=CC=C1 MXMQIRYBCYFUOK-UHFFFAOYSA-N 0.000 description 4
- TXFPEBPIARQUIG-UHFFFAOYSA-N 4'-hydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1 TXFPEBPIARQUIG-UHFFFAOYSA-N 0.000 description 4
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- CGEOWJVEIAILOR-UHFFFAOYSA-N ethyl 2-(4-formylphenoxy)acetate Chemical compound CCOC(=O)COC1=CC=C(C=O)C=C1 CGEOWJVEIAILOR-UHFFFAOYSA-N 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical compound OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 208000025865 Ulcer Diseases 0.000 description 3
- 210000001015 abdomen Anatomy 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- YVWJJQUUORDFCC-UHFFFAOYSA-N ethyl 2-(2-formylphenoxy)acetate Chemical compound CCOC(=O)COC1=CC=CC=C1C=O YVWJJQUUORDFCC-UHFFFAOYSA-N 0.000 description 3
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 231100000397 ulcer Toxicity 0.000 description 3
- QMYNUASZONCCEI-UHFFFAOYSA-N 2-(3-methylbut-2-enoxy)benzaldehyde Chemical compound CC(C)=CCOC1=CC=CC=C1C=O QMYNUASZONCCEI-UHFFFAOYSA-N 0.000 description 2
- ZWVHTXAYIKBMEE-UHFFFAOYSA-N 2-hydroxyacetophenone Chemical compound OCC(=O)C1=CC=CC=C1 ZWVHTXAYIKBMEE-UHFFFAOYSA-N 0.000 description 2
- ZCAMZJYDORGUOV-UHFFFAOYSA-N 4-(3-methylbut-2-enoxy)benzaldehyde Chemical compound CC(C)=CCOC1=CC=C(C=O)C=C1 ZCAMZJYDORGUOV-UHFFFAOYSA-N 0.000 description 2
- 229940073735 4-hydroxy acetophenone Drugs 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 208000008469 Peptic Ulcer Diseases 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 230000002467 anti-pepsin effect Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- KLAKIAVEMQMVBT-UHFFFAOYSA-N p-hydroxy-phenacyl alcohol Natural products OCC(=O)C1=CC=C(O)C=C1 KLAKIAVEMQMVBT-UHFFFAOYSA-N 0.000 description 2
- 208000011906 peptic ulcer disease Diseases 0.000 description 2
- 210000001187 pylorus Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- LOYZVRIHVZEDMW-UHFFFAOYSA-N 1-bromo-3-methylbut-2-ene Chemical compound CC(C)=CCBr LOYZVRIHVZEDMW-UHFFFAOYSA-N 0.000 description 1
- NGQJIEUOZYTRPF-UHFFFAOYSA-N 3-[2-(3-methylbuta-1,3-dienyl)phenyl]-1-phenylprop-2-en-1-one Chemical compound CC(=C)C=CC1=CC=CC=C1C=CC(=O)C1=CC=CC=C1 NGQJIEUOZYTRPF-UHFFFAOYSA-N 0.000 description 1
- UWDMKTDPDJCJOP-UHFFFAOYSA-N 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-ium-4-carboxylate Chemical compound CC1(C)CC(O)(C(O)=O)CC(C)(C)N1 UWDMKTDPDJCJOP-UHFFFAOYSA-N 0.000 description 1
- CONKBQPVFMXDOV-QHCPKHFHSA-N 6-[(5S)-5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-2-oxo-1,3-oxazolidin-3-yl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C[C@H]1CN(C(O1)=O)C1=CC2=C(NC(O2)=O)C=C1 CONKBQPVFMXDOV-QHCPKHFHSA-N 0.000 description 1
- QVTDXUBBWCTUSI-UHFFFAOYSA-N C(=CCC)OC1=C(C=O)C=CC=C1 Chemical compound C(=CCC)OC1=C(C=O)C=CC=C1 QVTDXUBBWCTUSI-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010042220 Stress ulcer Diseases 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 210000000013 bile duct Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- GCLGEJMYGQKIIW-UHFFFAOYSA-H sodium hexametaphosphate Chemical compound [Na]OP1(=O)OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])O1 GCLGEJMYGQKIIW-UHFFFAOYSA-H 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
Description
本発明は抗消化性潰瘍作用を有する新規なカル
コン化合物に関する。
更に詳しくは、本発明は、
一般式
〔式中、X1は３−メチル−２−ブテニロキシ基ま
たは水素原子を示し、X2、X3およびX4は同一か
または異なつて３−メチル−２−ブテニロキシ
基、カルボキシメトキシ基または水素原子を示
す。
（ただし、X2、X3およびX4のうち、１個はカルボ
キシメトキシ基を示す。その余のX1、X2、X3お
よびX4のうち、１個または２個は３−メチル−
２−ブテニロキシ基を示し、他の２個または１個
は水素原子を示す。またX3およびX4のうち、い
ずれか一方が３−メチル−２−ブテニロキシ基を
示すときは他方は水素原子または３−メチル−２
−ブテニロキシ基を示す。）〕で表わされるカルコ
ン化合物に関するものである。
一般式（）で示される本発明の化合物（以下
化合物（）と略称する。）は例えば次のように
して製造することができる。
即ち、
一般式
〔式中、Y1は前記X1と同義であり、Y2は前記X2と
同義である。ただし、前記X2がカルボキシメト
キシ基を示すときは、Y2は、
一般式
−OCH2COOR （）
（式中、Ｒは水素原子または低級アルキル基を示
す。）で表わされる。〕で表わされる化合物と、
一般式
（式中、Y3は前記X3と同義であり、Y4は前記X4と
同義である。ただし、前記X3またはX4がカルボ
キシメトキシ基を示すときは、それぞれY3また
はY4は、前記一般式（）で表わされる。）で表
わされる化合物とを、メタノール、エタノール、
アセトン、ｎ−ヘキサン、ベンゼンなどの有機溶
媒に溶解させ、水酸化カリウム、水酸化ナトリウ
ム、炭酸ナトリウム、炭酸カリウム、ナトリウム
メチラート、ナトリウムエチラートなどの塩基を
加えて、室温もしくは還流下に反応せしめて化合
物（）を製造する。
上記反応において、一方の出発原料であり、一
般式（）で表わされる化合物は、４−ハイドロ
キシアセトフエノンをメタノール、エタノール、
アセトン、エーテル、ベンゼンなどの有機溶媒に
溶解させ、水酸化カリウム、水酸化ナトリウム、
ナトリウムハイドライド、ナトリウムアルコラー
トなどの塩基を加えて室温でハロゲノ酢酸または
ハロゲノ酢酸低級アルキルエステルと反応させる
ことによつて得られるか、あるいは２・４−ジハ
イドロキシアセトフエノン、２−ハイドロキシア
セトフエノンまたは４−（低級アルコキシカルボ
ニルメトキシ）−２−ハイドロキシアセトフエノ
ンをメタノール、エタノール、アセトン、エーテ
ル、ベンゼンなどの有機溶媒に溶解させ、水酸化
カリウム、水酸化ナトリウム、炭酸カリウム、ナ
トリウムハイドライドなどの塩基を加えて室温で
３−メチル−２−ブテニルハロゲナイドを反応せ
しめることによつて得られる。その製造例を参考
例１〜４に示す。
もう一方の出発原料であり、一般式（）で表
わされる化合物は４−ハイドロキシベンズアルデ
ヒドまたは２−ハイドロキシベンズアルデヒドを
メタノール、エタノール、アセトン、エーテル、
ベンゼンなどの有機溶媒に溶解させ、炭酸カリウ
ム、炭酸ナトリウム、水酸化カリウム、水酸化ナ
トリウム、ナトリウムハイドライド、ナトリウム
アルコラートなどの塩基を加えて室温でハロゲノ
酢酸エチルを反応せしめることによつて得られ
る。
その製造例を参考例５〜６に示す。
参考例 １
４−ハイドロキシアセトフエノン１ｇをアセト
ン10mlに溶解し、無水炭酸カリウム２ｇを加えて
20分間撹拌後、アセトン５mlに溶解したα−ブロ
ム酢酸エチル1.5ｇを滴下し、室温で３時間撹拌
した。固型物を別後、アセトンを留去して４−
（エトキシカルボニルメトキシ）アセトフエノン
1.4ｇを得た。m.p.47〜50℃
参考例 ２
２・４−ジハイドロキシアセトフエノン10ｇを
アセトン200mlに溶解し、水酸化カリウム８ｇを
加え、20分間撹拌後、アセトン20mlに溶解した３
−メチル−２−ブテニルブロマイド25ｇを撹拌下
に滴加し、60℃で３時間撹拌した。固型物を別
し、アセトンを留去して、２・４−ビス−（３−
メチル−２−ブテニロキシ）アセトフエノン17ｇ
を得た。m.p.50〜53℃
参考例 ３
４−（エトキシカルボニルメトキシ）−２−ハイ
ドロキシアセトフエノン1.1ｇをアセトン15mlに
溶解し、水酸化カリウム0.3ｇを加えて20分間撹
拌後、７mlのアセトンに溶解した３−メチル−２
−ブテニルブロマイド1.0ｇを滴下し室温で４時
間撹拌した。固型物を別後、アセトンを留去し
て、油状の４−（エトキシカルボニルメトキシ）−
２−（３−メチル−２−ブテニロキシ）アセトフ
エノン1.2ｇを得た。
b.p.142〜145℃（0.7mmHg）
参考例 ４
２−ハイドロキシアセトフエノン１ｇをアセト
ン10mlに溶解し、無水炭酸カリウム２ｇを加えて
20分間撹拌後７mlのアセトンに溶解した３−メチ
ル−２−ブテニルブロマイド1.3ｇを滴下し、室
温で４時間撹拌した。固型物を別後、アセトン
を留去して油状の２−（３−メチル−２−ブテニ
ロキシ）アセトフエノン1.3ｇを得た。
b.p.145〜148℃（0.7mmHg）
参考例 ５
４−ハイドロキシベンズアルデヒド１ｇをアセ
トン10mlに溶解し、無水炭酸カリウム２ｇを加え
て20分間撹拌後、５mlのアセトンに溶解したα−
ブロム酢酸エチル1.5ｇを滴下し、室温で３時間
撹拌した。固型物を別後アセトンを留去して、
４−（エトキシカルボニルメトキシ）ベンズアル
デヒド1.5ｇを得た。
b.p.141〜148℃（0.6mmHg）
参考例 ６
２−ハイドロキシベンズアルデヒド１ｇをアセ
トン10mlに溶解し、無水炭酸カリウム２ｇを加え
て20分間撹拌後、５mlのアセトンに溶解したα−
ブロム酢酸エチル1.4ｇを滴下し、２時間還流し
た。固型物を別後アセトンを留去して、２−
（エトキシカルボニルメトキシ）ベンズアルデヒ
ド0.7ｇを得た。m.p.34〜36℃
本発明の化合物（）は抗消化性潰瘍作用がす
ぐれており、毒性が低いばかりでなく、カルボキ
シメトキシ基を有するために、この基を有しない
イソプレニルカルコンに比しすぐれた腸管吸収率
を示した。これらのすぐれた作用を明らかにする
ために試験例を次に示す。
試験例 １
ラツト各群10匹を用いて幽門結紮法（腹腔内投
与量50mg/Kg）およびストレス潰瘍法（腹腔内投
与量50mg/Kg）により実験潰瘍抑制率を求め、ま
たラツト各群10匹を用いて酢酸潰瘍法（経口投与
量100mg/Kg）により実験潰瘍治癒率を求め、表１
の結果を得た。
試験例 ２
ラツト各群３匹を予め24時間絶食させた後開腹
し、胃幽門部、胃幽門部から４cmのところの腸管
および胆管の３箇所を結紮して袋部を形成させ
た。この袋部に0.5％CMC水溶液に懸濁させた被
験薬（投与量100mg/Kg）を注入し、仮閉腹してか
ら３時間後に、再び開腹してこの袋部を切り取
り、被験薬の残量を定量し、吸収率を求め、表１
の結果を得た。
また、４−ハイドロキシ−2′・4′−ビス−（３
−メチル−２−ブテニロキシ）カルコン、２−ハ
イドロキシ−2′・4′−ビス−（３−メチル−２−
ブテニロキシ）カルコンおよび4′−ハイドロキシ
−2′・４−ビス−（３−メチル−２−ブテニロキ
シ）カルコンを対照薬として用い、これらについ
ても同様の試験を行なつた。
その吸収率はそれぞれ5.9％、6.5％および6.0％
であつた。
試験例 ３
マウス各群３匹に0.4％CMC溶液に懸濁させた
被験薬を経口投与し、72時間後の死亡率からリツ
チフイールド・ウイルソン法により急性毒性値
（LP50）を求め、表１の結果を得た。
The present invention relates to a novel chalcone compound having anti-peptic ulcer activity. More specifically, the present invention comprises the general formula [In the formula, X 1 represents a 3-methyl-2-butenyloxy group or a hydrogen atom, and X 2 , X 3 and X 4 are the same or different and represent a 3-methyl-2-butenyloxy group, a carboxymethoxy group or a hydrogen atom. shows. (However, one of X 2 , X 3 and X 4 represents a carboxymethoxy group. One or two of the remaining X 1 , X 2 , X 3 and X 4 are 3-methyl-
It represents a 2-butenyloxy group, and the other two or one represent a hydrogen atom. Furthermore, when either one of X 3 and X 4 represents a 3-methyl-2-butenyloxy group, the other represents a hydrogen atom or a 3-methyl-2-butenyloxy group.
- indicates a butenyloxy group. )]. The compound of the present invention represented by the general formula () (hereinafter abbreviated as compound ()) can be produced, for example, as follows. That is, the general formula [In the formula, Y 1 has the same meaning as the above-mentioned X 1 , and Y 2 has the same meaning as the above-mentioned X 2 . However, when X 2 represents a carboxymethoxy group, Y 2 is represented by the general formula -OCH 2 COOR (in the formula, R represents a hydrogen atom or a lower alkyl group). ] and the general formula (In the formula, Y 3 has the same meaning as the above X 3 , and Y 4 has the same meaning as the above X 4. However, when the above X 3 or X 4 represents a carboxymethoxy group, Y 3 or Y 4 respectively , a compound represented by the above general formula ()) is combined with methanol, ethanol,
Dissolve in an organic solvent such as acetone, n-hexane, or benzene, add a base such as potassium hydroxide, sodium hydroxide, sodium carbonate, potassium carbonate, sodium methylate, or sodium ethylate, and react at room temperature or under reflux. to produce compound (). In the above reaction, one of the starting materials, a compound represented by the general formula (), is obtained by converting 4-hydroxyacetophenone into methanol, ethanol,
Dissolve it in an organic solvent such as acetone, ether, benzene, etc., and add potassium hydroxide, sodium hydroxide,
It can be obtained by reacting with halogenoacetic acid or lower alkyl halogenoacetic acid ester at room temperature with the addition of a base such as sodium hydride, sodium alcoholate, or 2,4-dihydroxyacetophenone, 2-hydroxyacetophenone or 4-(Lower alkoxycarbonylmethoxy)-2-hydroxyacetophenone is dissolved in an organic solvent such as methanol, ethanol, acetone, ether, or benzene, and a base such as potassium hydroxide, sodium hydroxide, potassium carbonate, or sodium hydride is added. In addition, it can be obtained by reacting with 3-methyl-2-butenyl halide at room temperature. Production examples thereof are shown in Reference Examples 1 to 4. The other starting material, the compound represented by the general formula (), is 4-hydroxybenzaldehyde or 2-hydroxybenzaldehyde in methanol, ethanol, acetone, ether,
It can be obtained by dissolving it in an organic solvent such as benzene, adding a base such as potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, sodium hydride, sodium alcoholate, etc., and reacting it with ethyl halogenoacetate at room temperature. Production examples thereof are shown in Reference Examples 5 and 6. Reference example 1 Dissolve 1 g of 4-hydroxyacetophenone in 10 ml of acetone and add 2 g of anhydrous potassium carbonate.
After stirring for 20 minutes, 1.5 g of ethyl α-bromoacetate dissolved in 5 ml of acetone was added dropwise, and the mixture was stirred at room temperature for 3 hours. After separating the solids, acetone was distilled off and 4-
(ethoxycarbonylmethoxy)acetophenone
1.4g was obtained. mp47~50℃ Reference Example 2 10g of 2,4-dihydroxyacetophenone was dissolved in 200ml of acetone, 8g of potassium hydroxide was added, and after stirring for 20 minutes, 3 dissolved in 20ml of acetone
25 g of -methyl-2-butenyl bromide was added dropwise with stirring, and the mixture was stirred at 60°C for 3 hours. Separate the solids and distill off the acetone to obtain 2,4-bis-(3-
Methyl-2-butenyloxy)acetophenone 17g
I got it. mp50~53℃ Reference Example 3 1.1 g of 4-(ethoxycarbonylmethoxy)-2-hydroxyacetophenone was dissolved in 15 ml of acetone, 0.3 g of potassium hydroxide was added, and after stirring for 20 minutes, dissolved in 7 ml of acetone. -methyl-2
1.0 g of -butenyl bromide was added dropwise and stirred at room temperature for 4 hours. After separating the solids, acetone was distilled off to obtain oily 4-(ethoxycarbonylmethoxy)-
1.2 g of 2-(3-methyl-2-butenyloxy)acetophenone was obtained. bp142-145℃ (0.7mmHg) Reference example 4 Dissolve 1g of 2-hydroxyacetophenone in 10ml of acetone and add 2g of anhydrous potassium carbonate.
After stirring for 20 minutes, 1.3 g of 3-methyl-2-butenyl bromide dissolved in 7 ml of acetone was added dropwise, and the mixture was stirred at room temperature for 4 hours. After separating the solids, acetone was distilled off to obtain 1.3 g of oily 2-(3-methyl-2-butenyloxy)acetophenone. bp145-148℃ (0.7mmHg) Reference Example 5 1 g of 4-hydroxybenzaldehyde was dissolved in 10 ml of acetone, 2 g of anhydrous potassium carbonate was added, and after stirring for 20 minutes, α- dissolved in 5 ml of acetone was added.
1.5 g of ethyl bromoacetate was added dropwise, and the mixture was stirred at room temperature for 3 hours. After separating the solids, distill off the acetone,
1.5 g of 4-(ethoxycarbonylmethoxy)benzaldehyde was obtained. bp141-148℃ (0.6mmHg) Reference Example 6 Dissolve 1g of 2-hydroxybenzaldehyde in 10ml of acetone, add 2g of anhydrous potassium carbonate, stir for 20 minutes, and then dissolve α-benzaldehyde dissolved in 5ml of acetone.
1.4 g of ethyl bromoacetate was added dropwise, and the mixture was refluxed for 2 hours. After separating the solids, the acetone was distilled off and 2-
0.7 g of (ethoxycarbonylmethoxy)benzaldehyde was obtained. mp34-36℃ The compound () of the present invention not only has excellent anti-peptic ulcer activity and low toxicity, but also has a carboxymethoxy group, so it has a superior intestinal tract effect compared to isoprenyl chalcone, which does not have this group. The absorption rate was shown. Test examples are shown below to demonstrate these excellent effects. Test Example 1 The experimental ulcer suppression rate was determined by the pyloric ligation method (intraperitoneal dose 50 mg/Kg) and the stress ulcer method (intraperitoneal dose 50 mg/Kg) using 10 rats in each group. The experimental ulcer healing rate was determined by the acetic acid ulcer method (oral dose 100 mg/Kg) using Table 1.
The results were obtained. Test Example 2 After fasting 3 rats in each group for 24 hours, the abdomen was opened, and the gastric pylorus, the intestinal tract 4 cm from the gastric pylorus, and the bile duct were ligated to form a pouch. The test drug suspended in 0.5% CMC aqueous solution (dose 100 mg/Kg) was injected into this pouch, and 3 hours after the abdomen was temporarily closed, the abdomen was opened again and the pouch was cut out to remove the remaining test drug. Quantitate the amount and find the absorption rate, Table 1
The results were obtained. In addition, 4-hydroxy-2′・4′-bis-(3
-methyl-2-butenyloxy)chalcone, 2-hydroxy-2',4'-bis-(3-methyl-2-
Similar tests were conducted using 4'-hydroxy-2'-4-bis-(3-methyl-2-butenyloxy) chalcone and 4'-hydroxy-2'-2-butenyloxy) chalcone as control drugs. Its absorption rate is 5.9%, 6.5% and 6.0% respectively
It was hot. Test Example 3 The test drug suspended in 0.4% CMC solution was orally administered to 3 mice in each group, and the acute toxicity value (LP 50 ) was determined by the Richfield-Wilson method from the mortality rate after 72 hours. Table 1 The results were obtained.
【表】【table】
【表】
次に実施例を挙げて本発明を説明する。
実施例 １
４−（３−メチル−２−ブテニロキシ）アセト
フエノン1.3ｇと４−（エトキシカルボニルメトキ
シ）ベンズアルデヒド1.3ｇをエタノール10mlに
溶解させ、20％水酸化カリウム水溶液10mlを加え
て室温で４時間撹拌した。反応混合物に希塩酸を
加えて酸性としたのち、ジクロルメタンで抽出
後、水洗、乾燥し溶媒を留去し、残渣をエタノー
ルで再結晶して４−（カルボキシメトキシ）−4′−
（３−メチル−２−ブテニロキシ）カルコン0.4ｇ
を得た。m.p.154〜157℃（分解）
実施例 ２
４−（３−メチル−２−ブテニロキシ）アセト
フエノン1.3ｇと２−（エトキシカルボニルメトキ
シ）ベンズアルデヒド1.4ｇをエタノール５mlに
溶解させ、20％水酸化カリウム水溶液10mlを加え
て30℃で３時間撹拌した。反応混合物に希塩酸を
加えて酸性としたのち、ジクロルメタンで抽出
後、溶媒を留去し、エタノールで再結晶して、２
−（カルボキシメトキシ）−4′−（３−メチル−２
−ブテニロキシ）カルコン1.6ｇを得た。m.p.147
〜148℃
実施例 ３
４−（エトキシカルボニルメトキシ）アセトフ
エノン2.6ｇと４−（３−メチル−２−ブテニロキ
シ）ベンズアルデヒド2.2ｇをエタノール10mlに
溶解させ、20％水酸化カリウム水溶液20mlを加え
て撹拌下に１時間還流した。反応混合物に希塩酸
を加えて酸性としたのち、ジクロルメタンで抽出
後、溶媒を留去し、エタノールで再結晶して、
4′−（カルボキシメトキシ）−４−（３−メチル−
２−ブテニロキシ）カルゴン0.7ｇを得た。m.
p.144〜147℃
実施例 ４
４−（エトキシカルボニルメトキシ）アセトフ
エノン1.4ｇと２−（３−メチル−２−ブテニロキ
シ）ベンズアルデヒド1.2ｇをエタノール５mlに
溶解させ、20％水酸化カリウム水溶液10mlを加え
て室温で４時間撹拌した。反応混合物に希塩酸を
加えて酸性にすると結晶が析出した。この結晶を
水洗しイソプロピルアルコールで再結晶して、
4′−（カルボキシメトキシ）−２−（３−メチル−
２−ブテニロキシ）カルコン1.7ｇを得た。m.
p.109〜112℃
実施例 ５
２・４−ビス−（３−メチル−２−ブテニロキ
シ）アセトフエノン1.9ｇと４−（エトキシカルボ
ニルメトキシ）ベンズアルデヒド1.4ｇをエタノ
ール７mlに溶解させ、20％水酸化カリウム水溶液
13mlを加えて撹拌下１時間還流した。反応混合物
に希塩酸を加えて酸性としたのち、ジクロルメタ
ンで抽出し、溶媒を留去しエタノールで再結晶し
て、４−（カルボキシメトキシ）−2′・4′−ビス−
（３−メチル−２−ブテニロキシ）カルコン0.6ｇ
を得た。m.p.117〜120℃
実施例 ６
２・４−ビス−（３−メチル−２−ブテニロキ
シ）アセトフエノン1.9ｇと２−（エトキシカルボ
ニルメトキシ）ベンズアルデヒド1.4ｇをエタノ
ール７mlに溶解させ、20％水酸化カリウム水溶液
13mlを加えて室温で５時間撹拌した。反応混合物
に希塩酸を加えて酸性とした後、ジクロルメタン
で抽出し、溶媒を留去し、エタノールで再結晶し
て、２−（カルボキシメトキシ）−2′・4′−ビス−
（３−メチル−２−ブテニロキシ）カルコン1.4ｇ
を得た。m.p.140〜142℃
実施例 ７
４−（エトキシカルボニルメトキシ）アセトフ
エノン1.4ｇと２・４−ビス−（３−メチル−２−
ブテニロキシ）ベンズアルデヒド1.6ｇをエタノ
ール15mlに溶解させ、50％水酸化カリウム水溶液
20mlを加えて、室温で４時間撹拌した。反応混合
物に希塩酸を加えて酸性としたのち、ジクロルメ
タンで抽出後、溶媒を留去し、ｎ−ヘキサン−ア
セトン混液で再結晶して、4′−（カルボキシメト
キシ）−２・４−ビス−（３−メチル−２−ブテニ
ロキシ）カルコン0.8ｇを得た。m.p.147〜150℃
実施例 ８
４−（エトキシカルボニルメトキシ）−２−（３
−メチル−２−ブテニロキシ）アセトフエノン
1.5ｇと４−（３−メチル−２−ブテニロキシ）ベ
ンズアルデヒド１，０ｇをエタノール10mlに溶解
させ、20％水酸化カリウム水溶液20mlを加えて室
温で４時間撹拌した。反応混合物に希塩酸を加え
て酸性としたのち、ジクロルメタンで抽出後、溶
媒を留去し、イソプロピルアルコールで再結晶し
て4′−（カルボキシメトキシ）−2′・４−ビス−
（３−メチル−２−ブテニロキシ）カルコン0.5ｇ
を得た。m.p.146〜149℃
実施例 ９
４−（エトキシカルボニルメトキシ）−２−（３
−メチル−２−ブテニロキシ）アセトフエノン
1.5ｇと２−（３−メチル−２−ブテニロキシ）ベ
ンズアルデヒド1.0ｇをエタノール10mlに溶解さ
せ、20％水酸化カリウム水溶液20mlを加えて室温
で４時間撹拌した。反応混合物に希塩酸を加えて
酸性としたのち、ジクロルメタンで抽出後、溶媒
を留去し、イソプロピルアルコールで再結晶し
て、4′−（カルボキシメトキシ）−２・2′−ビス−
（３−メチル−２−ブテニロキシ）カルコン0.7ｇ
を得た。m.p.150〜152℃
実施例 10
２−（３−メチル−２−ブテニロキシ）アセト
フエノン1.5ｇと４−（エトキシカルボニルメトキ
シ）ベンズアルデヒド1.5ｇをエタノール７mlに
溶解させ、20％水酸化カリウム水溶液15mlを加え
て、室温で５時間撹拌した。反応混合物に希塩酸
を加えて酸性とした後、ジクロルメタンで抽出
し、溶媒を留去し、エタノールで再結晶して、４
−（カルボキシメトキシ）−2′−（３−メチル−２
−ブテニロキシ）カルコン1.0ｇを得た。m.p.144
〜147℃
実施例 11
２−（３−メチル−２−ブテニロキシ）アセト
フエノン1.5ｇと２−（エトキシカルボニルメトキ
シ）ベンジルアルデヒド1.5ｇをエタノール７ml
に溶解させ、20％水酸化カリウム水溶液15mlを加
えて、室温で４時間撹拌した。反応混合物に希塩
酸を加えて酸性とした後、ジクロルメタンで抽出
し、溶媒を留去し、エタノールで再結晶して、２
−（カルボキシメトキシ）−2′−（３−メチル−２
−ブテニロキシ）カルコン1.8ｇを得た。m.p.143
〜146℃
実施例 12
４−（エトキシカルボニルメトキシ）−２−（３
−メチル−２−ブテニロキシ）アセトフエノン
1.5ｇとベンズアルデヒド0.5ｇをエタノール10ml
に溶解させ、50％水酸化カリウム20mlを加えて室
温で４時間撹拌した。反応混合物に希塩酸を加え
て加えて酸性とした後、ジクロルメタンで抽出、
溶媒を留去して、イソプロピルアルコールで再結
晶して、4′−（カルボキシメトキシ）−2′−（３−
メチル−２−ブテニロキシ）カルコン0.4ｇを得
た。m.p.141〜143℃。[Table] Next, the present invention will be explained with reference to Examples. Example 1 1.3 g of 4-(3-methyl-2-butenyloxy)acetophenone and 1.3 g of 4-(ethoxycarbonylmethoxy)benzaldehyde were dissolved in 10 ml of ethanol, 10 ml of 20% aqueous potassium hydroxide solution was added, and the mixture was stirred at room temperature for 4 hours. did. The reaction mixture was made acidic by adding dilute hydrochloric acid, extracted with dichloromethane, washed with water, dried, the solvent was distilled off, and the residue was recrystallized with ethanol to give 4-(carboxymethoxy)-4'-
(3-methyl-2-butenyloxy) chalcone 0.4g
I got it. mp154-157℃ (decomposition) Example 2 1.3 g of 4-(3-methyl-2-butenyloxy)acetophenone and 1.4 g of 2-(ethoxycarbonylmethoxy)benzaldehyde were dissolved in 5 ml of ethanol, and 10 ml of a 20% aqueous potassium hydroxide solution was added. In addition, the mixture was stirred at 30°C for 3 hours. The reaction mixture was made acidic by adding diluted hydrochloric acid, extracted with dichloromethane, the solvent was distilled off, and recrystallized with ethanol.
-(carboxymethoxy)-4'-(3-methyl-2
-Butenyloxy)chalcone 1.6g was obtained. mp147
~148℃ Example 3 2.6 g of 4-(ethoxycarbonylmethoxy)acetophenone and 2.2 g of 4-(3-methyl-2-butenyloxy)benzaldehyde were dissolved in 10 ml of ethanol, and 20 ml of 20% aqueous potassium hydroxide solution was added thereto with stirring. The mixture was refluxed for 1 hour. The reaction mixture was made acidic by adding dilute hydrochloric acid, extracted with dichloromethane, the solvent was distilled off, and recrystallized with ethanol.
4'-(carboxymethoxy)-4-(3-methyl-
0.7 g of 2-butenyloxy) calgon was obtained. m.
p.144-147℃ Example 4 1.4 g of 4-(ethoxycarbonylmethoxy)acetophenone and 1.2 g of 2-(3-methyl-2-butenyloxy)benzaldehyde were dissolved in 5 ml of ethanol, and 10 ml of 20% potassium hydroxide aqueous solution was added. The mixture was stirred at room temperature for 4 hours. When the reaction mixture was made acidic by adding dilute hydrochloric acid, crystals were precipitated. The crystals were washed with water and recrystallized with isopropyl alcohol.
4'-(carboxymethoxy)-2-(3-methyl-
1.7 g of 2-butenyloxy) chalcone was obtained. m.
p.109-112℃ Example 5 Dissolve 1.9 g of 2,4-bis-(3-methyl-2-butenyloxy)acetophenone and 1.4 g of 4-(ethoxycarbonylmethoxy)benzaldehyde in 7 ml of ethanol, and dissolve 20% potassium hydroxide. aqueous solution
13 ml of the mixture was added and the mixture was refluxed for 1 hour while stirring. The reaction mixture was made acidic by adding dilute hydrochloric acid, extracted with dichloromethane, the solvent was distilled off, and recrystallized from ethanol to give 4-(carboxymethoxy)-2',4'-bis-
(3-methyl-2-butenyloxy) chalcone 0.6g
I got it. mp117~120℃ Example 6 Dissolve 1.9 g of 2,4-bis-(3-methyl-2-butenyloxy)acetophenone and 1.4 g of 2-(ethoxycarbonylmethoxy)benzaldehyde in 7 ml of ethanol, and add 20% aqueous potassium hydroxide solution.
13 ml was added and stirred at room temperature for 5 hours. The reaction mixture was made acidic by adding dilute hydrochloric acid, extracted with dichloromethane, the solvent was distilled off, and recrystallized from ethanol to give 2-(carboxymethoxy)-2',4'-bis-
(3-methyl-2-butenyloxy)chalcone 1.4g
I got it. mp140-142℃ Example 7 1.4 g of 4-(ethoxycarbonylmethoxy)acetophenone and 2,4-bis-(3-methyl-2-
Dissolve 1.6 g of (butenyloxy)benzaldehyde in 15 ml of ethanol and add 50% potassium hydroxide aqueous solution.
20 ml was added and stirred at room temperature for 4 hours. The reaction mixture was made acidic by adding diluted hydrochloric acid, extracted with dichloromethane, the solvent was distilled off, and recrystallized from a mixture of n-hexane and acetone to give 4'-(carboxymethoxy)-2,4-bis-( 0.8 g of 3-methyl-2-butenyloxy) chalcone was obtained. mp147-150℃ Example 8 4-(ethoxycarbonylmethoxy)-2-(3
-methyl-2-butenyloxy)acetophenone
1.5 g and 1.0 g of 4-(3-methyl-2-butenyloxy)benzaldehyde were dissolved in 10 ml of ethanol, 20 ml of a 20% aqueous potassium hydroxide solution was added, and the mixture was stirred at room temperature for 4 hours. The reaction mixture was made acidic by adding dilute hydrochloric acid, extracted with dichloromethane, the solvent was distilled off, and recrystallized from isopropyl alcohol to give 4'-(carboxymethoxy)-2',4-bis-
(3-methyl-2-butenyloxy) chalcone 0.5g
I got it. mp146-149℃ Example 9 4-(ethoxycarbonylmethoxy)-2-(3
-methyl-2-butenyloxy)acetophenone
1.5 g and 1.0 g of 2-(3-methyl-2-butenyloxy)benzaldehyde were dissolved in 10 ml of ethanol, 20 ml of a 20% aqueous potassium hydroxide solution was added, and the mixture was stirred at room temperature for 4 hours. The reaction mixture was made acidic by adding dilute hydrochloric acid, extracted with dichloromethane, the solvent was distilled off, and recrystallized from isopropyl alcohol to give 4'-(carboxymethoxy)-2.2'-bis-
(3-methyl-2-butenyloxy) chalcone 0.7g
I got it. mp150-152℃ Example 10 1.5 g of 2-(3-methyl-2-butenyloxy)acetophenone and 1.5 g of 4-(ethoxycarbonylmethoxy)benzaldehyde were dissolved in 7 ml of ethanol, and 15 ml of 20% potassium hydroxide aqueous solution was added. Stirred at room temperature for 5 hours. The reaction mixture was made acidic by adding dilute hydrochloric acid, extracted with dichloromethane, the solvent was distilled off, and recrystallized with ethanol.
-(carboxymethoxy)-2'-(3-methyl-2
-butenyloxy) chalcone (1.0 g) was obtained. mp144
~147℃ Example 11 1.5 g of 2-(3-methyl-2-butenyloxy)acetophenone and 1.5 g of 2-(ethoxycarbonylmethoxy)benzylaldehyde were added to 7 ml of ethanol.
15 ml of 20% aqueous potassium hydroxide solution was added, and the mixture was stirred at room temperature for 4 hours. The reaction mixture was made acidic by adding dilute hydrochloric acid, extracted with dichloromethane, the solvent was distilled off, and recrystallized with ethanol.
-(carboxymethoxy)-2'-(3-methyl-2
-Butenyloxy) chalcone (1.8 g) was obtained. mp143
~146℃ Example 12 4-(ethoxycarbonylmethoxy)-2-(3
-methyl-2-butenyloxy)acetophenone
1.5g and 0.5g of benzaldehyde in 10ml of ethanol
20 ml of 50% potassium hydroxide was added, and the mixture was stirred at room temperature for 4 hours. After adding dilute hydrochloric acid to the reaction mixture to make it acidic, extract with dichloromethane,
The solvent was distilled off and recrystallized from isopropyl alcohol to give 4'-(carboxymethoxy)-2'-(3-
0.4 g of methyl-2-butenyloxy) chalcone was obtained. mp141~143℃.
Claims (1)
たは水素原子を示し、X2、X3およびX4は同一か
または異なつて３−メチル−２−ブテニロキシ
基、カルボキシメトキシ基または水素原子を示
す。 （ただし、X2、X3およびX4のうち、１個はカルボ
キシメトキシ基を示す。その余のX1、X2、X3お
よびX4のうち、１個または２個は３−メチル−
２−ブテニロキシ基を示し、他の２個または１個
は水素原子を示す。またX3およびX4のうち、い
ずれか一方が３−メチル−２−ブテニロキシ基を
示すときは他方は水素原子または３−メチル−２
−ブテニロキシ基を示す。）〕で表わされるカルコ
ン化合物。[Claims] 1. General formula [In the formula, X 1 represents a 3-methyl-2-butenyloxy group or a hydrogen atom, and X 2 , X 3 and X 4 are the same or different and represent a 3-methyl-2-butenyloxy group, a carboxymethoxy group or a hydrogen atom. shows. (However, one of X 2 , X 3 and X 4 represents a carboxymethoxy group. One or two of the remaining X 1 , X 2 , X 3 and X 4 are 3-methyl-
It represents a 2-butenyloxy group, and the other two or one represent a hydrogen atom. Furthermore, when either one of X 3 and X 4 represents a 3-methyl-2-butenyloxy group, the other represents a hydrogen atom or a 3-methyl-2-butenyloxy group.
- indicates a butenyloxy group. )] is a chalcone compound.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8527977A JPS5419948A (en) | 1977-07-16 | 1977-07-16 | Chalcone compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8527977A JPS5419948A (en) | 1977-07-16 | 1977-07-16 | Chalcone compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5419948A JPS5419948A (en) | 1979-02-15 |
| JPS6115059B2 true JPS6115059B2 (en) | 1986-04-22 |
Family
ID=13854116
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8527977A Granted JPS5419948A (en) | 1977-07-16 | 1977-07-16 | Chalcone compounds |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5419948A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0545406Y2 (en) * | 1987-05-14 | 1993-11-19 |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8426424D0 (en) * | 1984-10-19 | 1984-11-28 | Biorex Laboratories Ltd | Chalcone derivatives |
-
1977
- 1977-07-16 JP JP8527977A patent/JPS5419948A/en active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0545406Y2 (en) * | 1987-05-14 | 1993-11-19 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5419948A (en) | 1979-02-15 |
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