JPH07121898B2 - Azulene derivative, antilipemic agent and method for producing the same - Google Patents
Azulene derivative, antilipemic agent and method for producing the sameInfo
- Publication number
- JPH07121898B2 JPH07121898B2 JP15024688A JP15024688A JPH07121898B2 JP H07121898 B2 JPH07121898 B2 JP H07121898B2 JP 15024688 A JP15024688 A JP 15024688A JP 15024688 A JP15024688 A JP 15024688A JP H07121898 B2 JPH07121898 B2 JP H07121898B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- general formula
- carbonyl
- glycinamide
- 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 - Lifetime
Links
- 239000003524 antilipemic agent Substances 0.000 title claims description 8
- HPJYKMSFRBJOSW-JHSUYXJUSA-N Damsin Chemical compound C[C@H]1CC[C@H]2C(=C)C(=O)O[C@H]2[C@]2(C)C(=O)CC[C@@H]12 HPJYKMSFRBJOSW-JHSUYXJUSA-N 0.000 title claims description 6
- 238000004519 manufacturing process Methods 0.000 title claims 2
- 150000001875 compounds Chemical class 0.000 claims description 30
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910021529 ammonia Inorganic materials 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 1
- BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 description 25
- -1 azulen-1-carbonyl Chemical group 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 229940125904 compound 1 Drugs 0.000 description 3
- 229940125782 compound 2 Drugs 0.000 description 3
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- VLNZUSMTOFYNPS-UHFFFAOYSA-N diethylphosphorylformonitrile Chemical compound CCP(=O)(CC)C#N VLNZUSMTOFYNPS-UHFFFAOYSA-N 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 230000002688 persistence Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- HGLFWLLFPGIKOT-UHFFFAOYSA-N azulene-1-carboxylic acid Chemical compound C1=CC=CC=C2C(C(=O)O)=CC=C21 HGLFWLLFPGIKOT-UHFFFAOYSA-N 0.000 description 1
- 150000001545 azulenes Chemical class 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- QQVDYSUDFZZPSU-UHFFFAOYSA-M chloromethylidene(dimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)=CCl QQVDYSUDFZZPSU-UHFFFAOYSA-M 0.000 description 1
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 1
- 229960001214 clofibrate Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】 産業上の利用分野 本発明は、新規アズレン誘導体、及びその製法並びに該
新規化合物の抗脂血剤としての応用に関する。TECHNICAL FIELD The present invention relates to a novel azulene derivative, a process for producing the same, and an application of the novel compound as an antilipemic agent.
従来技術及び問題点 アズレン誘導体のエステルが、抗脂血剤として有用であ
ることを開示した文献としては、特開昭60−156611など
が知られている。しかしながら、これらは薬効の持続性
や肝臓への影響などの点で必ずしも満足すべきものでな
く、より優れた且つ安全性の高い抗脂血剤が望まれてい
る。2. Description of the Related Art JP-A-60-156611 is known as a document disclosing that an ester of an azulene derivative is useful as an antilipemic agent. However, these are not always satisfactory in terms of the persistence of drug effect and the effect on the liver, and a superior and highly safe antilipemic agent is desired.
発明の構成 このような事情に対処して、本発明者は、より優れたア
ズレン誘導体を探求していた際、側鎖にグリシンアミド
を有する一連のアズレン誘導体が、薬効の持続性に優
れ、且つ、安全性の点でも従来の化合物に比べて優れて
いる事実に到達したものである。Constitution of the invention In response to such a situation, the present inventor was searching for a more excellent azulene derivative, and a series of azulene derivatives having a glycine amide in the side chain thereof were excellent in persistence of medicinal effect, and However, it has reached the fact that it is superior to conventional compounds in terms of safety.
本発明に係る化合物は、一般式（Ｉ）： （但し、式中、R1及びR2は、夫々、水素又は低級アルキ
ル基を表す。） で示されるアズレン誘導体である。The compound according to the present invention has the general formula (I): (However, in the formula, R 1 and R 2 each represent hydrogen or a lower alkyl group.).
上記一般式（Ｉ）で表わされる化合物のいくつかは次に
例示する。Some of the compounds represented by the above general formula (I) are exemplified below.
（１）Ｎ−（アズレン−１−カルボニル）グリシンアミ
ド（化合物１） （２）Ｎ−（３−メチルアズレン−１−カルボニル）グ
リシンアミド（化合物２） （３）Ｎ−（３−エチルアズレン−１−カルボニル）グ
リシンアミド（化合物３） （４）Ｎ−（７−イソプロピルアズレン−１−カルボニ
ル）グリシンアミド（化合物４） （５）Ｎ−（６−イソプロピルアズレン−１−カルボニ
ル）グリシンアミド（化合物５） （６）Ｎ−（３−エチル−７−イソプロピルアズレン−
１−カルボニル）グリシンアミド（化合物６） （７）Ｎ−（３−エチル−６−イソプロピルアズレン−
１−カルボニル）グリシンアミド（化合物７） 上記（１）、（２）、…（７）の化合物は、化合物１、
化合物２、…化合物７として引用される。(1) N- (azulen-1-carbonyl) glycinamide (compound 1) (2) N- (3-methylazulen-1-carbonyl) glycinamide (compound 2) (3) N- (3-ethylazulene- 1-carbonyl) glycinamide (compound 3) (4) N- (7-isopropylazulen-1-carbonyl) glycinamide (compound 4) (5) N- (6-isopropylazulen-1-carbonyl) glycinamide (compound 5) (6) N- (3-ethyl-7-isopropylazulene-
1-carbonyl) glycinamide (compound 6) (7) N- (3-ethyl-6-isopropylazulene-
1-Carbonyl) glycinamide (Compound 7) The compounds of (1), (2), ... (7) are compound 1,
Compound 2, ... Cited as Compound 7.
一般式Ｉで示される本願化合物は、 一般式II: （但し、式中、R1及びR2は、夫々、水素又は低級アルキ
ル基を表す。） で示されるアズレン−１−カルボン酸と、 一般式III: H2NCH2COOR3…（III） （但し、式中、R3は低級アルキル基を表わす。）で示さ
れるグリシンエステル類を、縮合剤の存在下で反応さ
せ、 一般式（IV）： （但し、式中、R1及びR2は、夫々、水素又は低級アルキ
ル基を、R3は低級アルキル基を表す。）で示される化合
物としたのち、アンモニアと反応させ、一般式（Ｉ）： （但し、式中、R1及びR2は、夫々、水素又は低級アルキ
ル基を表す。） で示されるアズレン誘導体を得ることが出来る。The compound of the present invention represented by the general formula I is represented by the general formula II: (However, in the formula, R 1 and R 2 each represent hydrogen or a lower alkyl group.) And an azulene-1-carboxylic acid represented by the general formula III: H 2 NCH 2 COOR 3 (III) ( However, in the formula, R 3 represents a lower alkyl group.), A glycine ester represented by the formula (IV): (However, in the formula, R 1 and R 2 are each a hydrogen atom or a lower alkyl group, and R 3 is a lower alkyl group.) After reacting with ammonia, the compound represented by the general formula (I) : (However, in the formula, R 1 and R 2 each represent hydrogen or a lower alkyl group.).
一般式（II）と一般式（III）の反応に用いる縮合剤と
しては、ジシクロヘキシルカルボジイミド、ジエチルホ
スホリルシアナイド或いはジフェニルホスホリルアジ
ド、或いはジメチルホルムアミドとオキシ塩化燐より作
ったビルスマイヤー試薬等が用いられる。ジエチルホス
ホリルシアナイド或いはジフェニルホスホリルアジドの
場合は、当量のトリエチルアミンの様な、アミンの存在
下に行なうことが良い。溶媒としてはジメチルホルムア
ミド或いはテトラヒドロフラン等が挙げられる。得られ
た一般式（IV）の化合物はアルコール中でアンモニアで
反応することにより、一般式（Ｉ）の化合物を得る。As the condensing agent used in the reaction between the general formulas (II) and (III), dicyclohexylcarbodiimide, diethylphosphoryl cyanide or diphenylphosphoryl azide, or Vilsmeier reagent prepared from dimethylformamide and phosphorus oxychloride can be used. In the case of diethylphosphoryl cyanide or diphenylphosphoryl azide, it may be carried out in the presence of an equivalent amount of amine such as triethylamine. Examples of the solvent include dimethylformamide, tetrahydrofuran and the like. The obtained compound of general formula (IV) is reacted with ammonia in alcohol to obtain the compound of general formula (I).
このようにして得られた本願化合物は、優れた低コレス
テロール作用を示し、抗脂血剤として有用である。The compound of the present invention thus obtained exhibits an excellent low cholesterol action and is useful as an antilipemic agent.
本願化合物は抗脂血剤として、経口、非経口いずれの経
路においても投与でき、成人１日当り30mg〜200mgの範
囲で用いることにより、所期の効果が得られるものと期
待される。The compound of the present invention can be administered as an antilipemic agent by either oral or parenteral routes, and it is expected that the desired effect can be obtained by using it in the range of 30 mg to 200 mg per day for an adult.
［薬理試験例１］ 本化合物の低コレステロール作用について、薬学雑誌
（92巻 1972年 879〜885p.）に記載されている天正明
等の方法によりテストした結果を表１に示す。これは体
重100gのウィスター系雄性ラットを用いて、１群を10匹
とし、本化合物を投与した群及び対照群とに分け、本化
合物を１％カルボキシメチルセルロースに懸濁して経口
投与したものである。[Pharmacological Test Example 1] Table 1 shows the results of the low cholesterol action of the present compound tested by the method of Tensho Akira et al. Described in Pharmaceutical Journal (Vol. 92, 1972, 879-885 p.). This is a group of 10 Wistar male rats weighing 100 g, which were divided into a group to which this compound was administered and a control group, and this compound was orally administered by suspending it in 1% carboxymethylcellulose. .
［薬理試験例２］ 本願化合物の肝機能への副作用を検定するため、ウィス
ター系雄性ラットに本願化合物を経口投与し、標準薬と
しては、抗脂血剤として現在臨床で用いられているクロ
フィブレートを用い、肝重量の増加率を体重に対する百
分率（％）で表わした。結果を表２に示す。 [Pharmacological Test Example 2] In order to test the side effect of the compound of the present invention on liver function, the compound of the present invention is orally administered to male Wistar rats, and as the standard drug, clofib, which is currently clinically used as an antilipemic agent, is administered. The rate of increase in liver weight was expressed as a percentage (%) with respect to body weight using the rate. The results are shown in Table 2.
上表から明らかなように、クロフィブレート投与群で
は、肝重量の増加が認められるが、本願化合物投与群で
は、肝重量の増加は殆ど認められない。 As is clear from the above table, the liver weight increases in the clofibrate administration group, but the liver weight hardly increases in the compound administration group of the present invention.
［製剤例１］ 顆粒剤 化合物６ 50mg 乳糖 40mg コーンスターチ 57mg メチルセルロース 3mg 合 計 150mg 上記組成の混合物を常法により顆粒剤とする。[Formulation Example 1] Granules Compound 6 50 mg Lactose 40 mg Corn starch 57 mg Methyl cellulose 3 mg Total 150 mg The mixture having the above composition is made into granules by a conventional method.
［製剤例２］ 錠剤 化合物６ 30mg 乳糖 30mg コーンスターチ 45mg メチルセルロース 3mg ステアリン酸マグネシウム 2mg 合 計 110mg 上記組成の混合物を常法により錠剤とする。[Formulation Example 2] Tablet Compound 6 30 mg Lactose 30 mg Corn starch 45 mg Methyl cellulose 3 mg Magnesium stearate 2 mg Total 110 mg A mixture of the above composition is made into tablets by a conventional method.
［実施例１］ Ｎ−（アズレン−１−カルボニル）グリシンアミド（化
合物１） （１）Ｎ−（アズレン−１−カルボニル）グリシンメチ
ルエステル アズレン1.0gとグリシンメチルエステル・塩酸塩0.88g
をジメチルホルムアミド20mlに加え、０℃にてジフェニ
ルホスホリルアジド1.5mlとトリエチルアミン2.1mlを加
えたのち、室温で４時間撹拌後、氷水にあけ、酢酸エチ
ルエステルで抽出する。酢酸エチル抽出液を水洗、脱水
後、乾燥（Na2SO4）して溶媒を留去する。残留物をシリ
カゲルを用いてカラムクロマトグラフィーを行なう（溶
出液：エーテル）。目的物1.2gを得る。[Example 1] N- (azulen-1-carbonyl) glycinamide (Compound 1) (1) N- (azulen-1-carbonyl) glycine methyl ester Azulene 1.0 g and glycine methyl ester / hydrochloride 0.88 g
Was added to 20 ml of dimethylformamide, 1.5 ml of diphenylphosphoryl azide and 2.1 ml of triethylamine were added at 0 ° C., the mixture was stirred at room temperature for 4 hours, poured into ice water, and extracted with ethyl acetate. The ethyl acetate extract is washed with water, dehydrated and dried (Na 2 SO 4 ) to remove the solvent. The residue is subjected to column chromatography using silica gel (eluent: ether). Obtain 1.2 g of the desired product.
M.S.（m/e）243（M+）,155（B.P.） （２）Ｎ−（アズレン−１−カルボニル）グリシンアミ
ド （１）で得た化合物1.2gに10％アルコール性アンモニア
液10mlを加え一夜放置する。反応液を減圧濃縮し、生じ
た結晶をエーテルで洗浄する。目的物0.79gを得る。MS (m / e) 243 (M + ), 155 (BP) (2) N- (azulen-1-carbonyl) glycinamide (1) To 1.2 g of the compound obtained in 10% alcoholic ammonia solution (10 ml) was added overnight. put. The reaction solution is concentrated under reduced pressure and the resulting crystals are washed with ether. Obtain 0.79 g of the desired product.
M.S.（m/e）228（M+）,155（B.P.） I.R.（cm-1）3310,3140,1689,1608,1548,1416,1398,128
7,1254,771,663 融点 82〜84℃ ［実施例１］と同様にして以下の化合物を得た。MS (m / e) 228 (M + ), 155 (BP) IR (cm -1 ) 3310,3140,1689,1608,1548,1416,1398,128
7,1254,771,663 Melting point 82-84 ° C. The following compound was obtained in the same manner as in [Example 1].
［実施例２］ Ｎ−（３−メチルアズレン−１−カルボニル）グリシン
アミド（化合物２） M.S.（m/e）243（M+＋１）,198,142（B.P.）,116,89 I.R.（cm-1）3364,1692,1671,1536,1440,1362,1242,768 融点 72〜73℃ ［実施例３］ Ｎ−（３−エチルアズレン−１−カルボニル）グリシン
アミド（化合物３） M.S.（m/e）256（M+）,242,183（B.P.）,138,109. I.R.（cm-1）3418,1692,1656,1614,1536,1503,1443,137
4,1224 融点 76〜78℃ ［実施例４］ Ｎ−（７−イソプロピルアズレン−１−カルボニル）グ
リシンアミド（化合物４） M.S.（m/e）271（M+＋１）,226,197（B.P.）,152,109 I.R.（cm-1）3358,1677,1620,1581,1530,1455,1266,102
9,804 融点 98〜100℃ ［実施例５］ Ｎ−（６−イソプロピルアズレン−１−カルボニル）グ
リシンアミド（化合物５） M.S.（m/e）271（M+＋１）,257,183（B.P.）,140,115,8
4 I.R.（cm-1）3418,1680,1620,1581,1548,1446,1227,103
5,843 融点 118〜120℃ ［実施例６］ Ｎ−（３−エチル−７−イソプロピルアズレン−１−カ
ルボニル）グリシンアミド（化合物６） M.S.（m/e）313（M+−１）,298,283（B.P.）,225,196,1
65,139,115,76 I.R.（cm-1）3328,1674,1614,1536,1461,1428,1383,131
7,1275,1248,780 融点 192〜194℃ ［実施例７］ Ｎ−（３−エチル−６−イソプロピルアズレン−１−カ
ルボニル）グリシンアミド（化合物７） M.S.（m/e）313（M+−１）,298（B.P.）,283,225,196,1
65,141,115,91 I.R.（cm-1）3328,1668,1620,1584,1515,1428,1269,105
0,850 融点 98〜99℃[Example 2] N- (3-methylazulene-1-carbonyl) glycinamide (Compound 2) MS (m / e) 243 (M + +1), 198,142 (BP), 116,89 IR (cm -1 ) 3364,1692,1671,1536,1440,1362,1242,768 Melting point 72-73 ° C [Example 3] N- (3-ethylazulene-1-carbonyl) glycinamide (Compound 3) MS (m / e) 256 (M + ), 242,183 (BP), 138,109.IR (cm -1 ) 3418,1692,1656,1614,1536,1503,1443,137
4,1224 Melting point 76-78 ° C [Example 4] N- (7-isopropylazulene-1-carbonyl) glycinamide (Compound 4) MS (m / e) 271 (M + +1), 226,197 (BP), 152,109 IR (cm -1 ) 3358,1677,1620,1581,1530,1455,1266,102
9,804 Melting point 98-100 ° C. [Example 5] N- (6-isopropylazulene-1-carbonyl) glycinamide (Compound 5) MS (m / e) 271 (M + +1), 257,183 (BP), 140,115,8
4 IR (cm -1 ) 3418,1680,1620,1581,1548,1446,1227,103
5,843 melting point 118 to 120 ° C. [Example 6] N- (3-ethyl-7-isopropylazulene-1-carbonyl) glycinamide (Compound 6) MS (m / e) 313 (M + -1), 298,283 (BP ), 225,196,1
65,139,115,76 IR (cm -1 ) 3328,1674,1614,1536,1461,1428,1383,131
7,1275,1248,780 Melting point 192-194 ° C. [Example 7] N- (3-ethyl-6-isopropylazulen-1-carbonyl) glycinamide (Compound 7) MS (m / e) 313 (M + − 1), 298 (BP), 283,225,196,1
65,141,115,91 IR (cm -1 ) 3328,1668,1620,1584,1515,1428,1269,105
0,850 Melting point 98-99 ℃
Claims (3)
ル基を表す。） で示されるアズレン誘導体。1. A general formula: (However, in the formula, R 1 and R 2 each represent hydrogen or a lower alkyl group.)
体を有効成分として含有する抗脂血剤。2. An antilipemic agent containing the azulene derivative according to claim 1 as an active ingredient.
基を表す。以下この項において同じ。）で示される化合
物と、一般式： NH2CH2COOR3 （但し、式中、R3は低級アルキル基を表わす。以下この
項において同じ。） で示される化合物とを、縮合剤の存在下において、反応
させることによって得られる一般式： で示される化合物を、アンモニアと反応させることを特
徴とする、 一般式： で示されるアズレン誘導体の製造方法。3. A general formula: (In the formula, R 1 and R 2 each represent hydrogen or a lower alkyl group. The same applies in the following in this section.) And a compound represented by the general formula: NH 2 CH 2 COOR 3 (in the formula, , R 3 represents a lower alkyl group, and the same applies hereinafter in this section) in the presence of a condensing agent, to obtain a general formula: A compound represented by the formula: is reacted with ammonia; A method for producing an azulene derivative represented by.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15024688A JPH07121898B2 (en) | 1988-06-20 | 1988-06-20 | Azulene derivative, antilipemic agent and method for producing the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15024688A JPH07121898B2 (en) | 1988-06-20 | 1988-06-20 | Azulene derivative, antilipemic agent and method for producing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH023643A JPH023643A (en) | 1990-01-09 |
| JPH07121898B2 true JPH07121898B2 (en) | 1995-12-25 |
Family
ID=15492754
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15024688A Expired - Lifetime JPH07121898B2 (en) | 1988-06-20 | 1988-06-20 | Azulene derivative, antilipemic agent and method for producing the same |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH07121898B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH10182546A (en) * | 1996-12-25 | 1998-07-07 | Kotobuki Seiyaku Kk | Azulene derivative, method for producing the same, and drug containing the same |
-
1988
- 1988-06-20 JP JP15024688A patent/JPH07121898B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH023643A (en) | 1990-01-09 |
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