KR950013576B1 - Pyranoindoles acetic aluminium compound and process for preparing the same - Google Patents
Pyranoindoles acetic aluminium compound and process for preparing the same Download PDFInfo
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본 발명은 소염진통작용을 갖는 피라노인돌 아세트산 알루미늄화합물 및 그의 제조법에 관한 것으로, 더욱 상세하게는 1,8-디에칠-1,3,4,9-테트라하이드로피라노[3,4,b]인돌-1-아세트산의 알루미늄염인 하기 일반식(Ⅰ)로 표시되는 피라노인돌 아세트산 알루미늄화합물 및 그의 제조법에 관한 것이다.The present invention relates to a pyranoindole aluminum acetate compound having an anti-inflammatory analgesic action and a preparation method thereof, and more particularly to 1,8-diethyl-1,3,4,9-tetrahydropyrano [3,4, b ] Pyranoindole aluminum acetate compound represented by the following general formula (I) which is an aluminum salt of indole-1-acetic acid, and its manufacturing method.
상기 식에서 n은 각각 1-3이 정수이다.Wherein n is an integer of 1-3, respectively.
모핵으로 피라노인돌 아세트산 구조를 갖는 화합물은 소염진통작용을 갖으며, 그 대표적인 화합물은 1,8-디에칠-1,3,4,9-테트라하이드로피라노[3,4,b]인돌-1-아세트산으로 명명되는 에토돌산(또는 에토돌락)으로 알려져 있으며, 미국특허 제 3843681호, 제 3939178호 등에 그의 제법이 소개되어 있다. 그의 소염작용 및 진통작용에 의한 류마치스성관절염등에 대한 효과는 쟈콥등에 의해 Curr. Ther. Res. 37, 1124(1985)에 상세히 알려져 있다. 그러나 에토돌산은 유리산 형태이어서 위장관 출혈이 유발될 수 있어 장기간 투여시는 제산제와의 병용투여가 권장되며, 또한 혈소판기능을 억제하는 등의 부작용이 있으며, 1일 1200mg씩 1주간 복용 및 1일 600mg 이상씩 장기간 복용시에는 안정성이 문제시 되고 있다.Compounds having a pyranoindole acetic acid structure as the parent nucleus have anti-inflammatory analgesic action, and a typical compound thereof is 1,8-diethyl-1,3,4,9-tetrahydropyrano [3,4, b] indole- Known as etodolic acid (or etodolak), designated 1-acetic acid, its preparation is introduced in U.S. Patent Nos. 3843681, 3939178 and the like. Its effect on anti-inflammatory and analgesic effects on rheumatoid arthritis is described by Jacob et al. In Curr. Ther. Res. 37, 1124 (1985). However, etodolic acid is a free acid form, which can cause gastrointestinal bleeding. Therefore, it is recommended to co-administer with antacids for long-term administration, and also has side effects such as inhibiting platelet function. Long-term use of more than 600mg stability is a problem.
따라서, 소염 및 진통작용은 대등하나 제산제의 병용투여없이도 위장관의 자극을 없애고 장기간연용 또는 대량 복용에 접하도록 에토돌산의 제제를 연구하던 중 본 발명의 화합물을 발견하고 특허로서 출원하기에 이른 것이다.Thus, while anti-inflammatory and analgesic action is comparable, the compounds of the present invention have been discovered and filed as patents while studying the preparation of etodolic acid to eliminate irritation of the gastrointestinal tract and contact prolonged or large doses without the use of antacids.
본 발명의 일반식(Ⅰ) 화합물중 대표적인 화합물로는 1) n=1인 경우의 피라노인돌아세트산(에토돌산)의 알루미늄염(1:1), 즉 1,8-디에칠-1,3,4,9-테트라하이드로피라노[3,4-b]인돌-1-아세트산 디하이드로옥시 알루미늄[C17H20NO3Al(OH)2], 2) n=2인 경우의 피라노인돌아세트산(에토돌산)의 알루미늄염 (2:1), 즉 디[1,8-디에칠-1,3,4,9-테트라하이드로 피라노[3,4-b]인돌-1-아세트산]모노하이드로옥시 알루미늄[(C17H20NO3)2Al(OH)], 3) n=3인 경우의 피라노인돌아세트산(에토돌산)의 알루미늄염 (3:1), 즉 트리[1,8-디에칠-1,3,4,9-테트라하이드로 피라노[3,4-b]인돌-1-아세트산]알루미늄[(C17H20NO3)3Al]이 있다.Representative compounds of the general formula (I) compounds of the present invention include 1) aluminum salts of pyranoindolacetic acid (ethodolic acid) when n = 1, i.e., 1,8-dimethyl-1,3 , 4,9-tetrahydropyrano [3,4-b] indole-1-acetic acid dihydrooxy aluminum [C 17 H 20 NO 3 Al (OH) 2 ], 2) Pyranonodol when n = 2 Aluminum salt of acetic acid (etodol acid) (2: 1), ie di [1,8-diethyl-1,3,4,9-tetrahydro pyrano [3,4-b] indole-1-acetic acid] mono Hydrooxyaluminum [(C 17 H 20 NO 3) 2 Al (OH)], 3) aluminum salt of pyranoindolacetic acid (etodolic acid) when n = 3 (3: 1), ie tri [1,8 -Diech-1,3,4,9-tetrahydro pyrano [3,4-b] indole-1-acetic acid] aluminum [(C 17 H 20 NO 3) 3 Al].
본 발명의 일반식(Ⅰ) 화합물은 에토돌사나트륨염 또는 에토돌산에 알카리존재하에 AlX3(여기서, X는 염소, 브롬등 할로겐 또는 질산, 황산등의 음이온을 나타냄)로 표시되는 알루미늄화합물을 수용액에서 화학 양론적으로 반응시킴으로써 이루어진다.The general formula (I) compound of the present invention is an aqueous solution of an aluminum compound represented by AlX 3 (where X represents an anion such as chlorine or bromine or nitric acid or sulfuric acid) in the presence of alkali in etodol-sodium salt or etodol acid. By stoichiometric reaction at.
이 반응은 통상 에토돌산을 물에 현탁시키고, 교반하여 수산화알카리(수산화칼륨 또는 수산화나트륨)존재하, 바람직하게는 수산화나트륨 수용액을 가하여 나트륨염으로 용해 변환시킨 다음, 알루미늄염의 수용액을 적가하여 반응시켜 제조한다.The reaction is usually carried out by suspending the etodol acid in water, stirring to the presence of alkali hydroxides (potassium hydroxide or sodium hydroxide), preferably adding sodium hydroxide solution to dissolve it into sodium salt, and then reacting by dropwise addition of an aqueous solution of aluminum salt. Manufacture.
또한, 변형방법으로 에토돌산에 Al(OR)3(여기서, R은 메칠, 에칠, 프로필, 이소푸로필등 저급 알킬기를 나타냄)로 표시되는 알루미늄 알콕싸이드(예, 알루미늄 이소프로폭싸이드등)를 반응시 제조한다. 이때에는 원료 에토돌산을 벤젠이나 톨루엔등 방향족 탄화수소류나, 메타놀, 에타놀, 푸로파놀, 이소푸로파놀등의 저급 알콜류등의 유기용제에 용해시켜서 반응시킨다.In addition, aluminum alkoxides (e.g., aluminum isopropoxide, etc.) represented by Al (OR) 3 (where R represents lower alkyl groups such as methyl, ethyl, propyl, and isofurophyll) in the etodol acid may be modified. Prepared during the reaction. At this time, the raw material etodol acid is dissolved in an organic solvent such as aromatic hydrocarbons such as benzene or toluene, and lower alcohols such as methanol, ethanol, furanol, isopuranol, and the like.
상기 두가지 방법중 어느 경우에 있어서나 에토돌산의 알루미늄에 대한 몰비를 대략 1~3몰로 조정함으로서 상기 일반식(Ⅰ)중의 n이 각각 1~3인 목적물을 얻을 수 있다.In either of the two methods described above, by adjusting the molar ratio of etodol acid to aluminum to approximately 1 to 3 moles, the targets having n in the general formula (I) of 1 to 3 can be obtained.
이리하여 얻어지는 일반식(Ⅰ)의 피라노인돌아세트산 알루미늄화합물(이하, 에토돌산 알루미늄이라 약칭한다. ), 즉 에토돌산 알루미늄염들은 문헌 미기재 신규화합물로 소염진통작용이 있을 뿐만 아니라 그의 제산 및 완충작용으로 인해서 유리산인 에토돌산(에토돌락)과 같이 위장관을 자극하지 않음으로서 제산제의 병용투여가 필요없고, 특히 장기간의 연용 또는 대량 복용에 적합하였다.The pyranoindoleacetic acid aluminum compound of the general formula (I) thus obtained (hereinafter abbreviated as aluminum etodolate), ie, aluminum etodolate, is an unlisted novel compound that has anti-inflammatory analgesic action as well as its antacid and buffering action. Due to the fact that it does not irritate the gastrointestinal tract like the free acid etodolic acid (etodolac), it is not necessary to use antacids in combination, and is particularly suitable for long-term use or large doses.
다음 표 1에 본 발명에 따른 에토돌산 알루미늄염들의 폴리소르베이트 80의 1% 용액에 현탁시킨액들의 pH를 에토돌산과 비교하여 나타냈다.Table 1 shows the pH of the solutions suspended in a 1% solution of polysorbate 80 of the etodol acid aluminum salts according to the present invention in comparison to etodol acid.
[표 1] 에토톨산알루미늄염들 및 에토돌산의 pHTable 1 pH of aluminum etotolate and etodolic acid
또한, 에토돌산은 그 맛이 쓰고 심히 불쾌한 산미를 시키고 있어 피복정이나 교갑제로 시판투여되고 있으나 본 발명의 알루미늄염은 복용 즉시는 거의 무미이므로 피복정으로 하지 않고도 복용할 수 있어 단위투여제형으로 투여하기 위한 약학적 현탁액제 또는 기타 고형제제에 배합하는 등 복용에 편리하고 효과적인 제제형을 만들 수 있는 장점이 있다.In addition, etodolic acid has a taste and is very unpleasant acidity and is commercially administered as a coated tablet or a staple medicine, but the aluminum salt of the present invention can be taken without a coated tablet because it is almost tasteless immediately after administration. It is advantageous to make a convenient and effective dosage form such as compounding to a pharmaceutical suspension or other solid preparations for the purpose.
본 발명의 화합물의 소염진통작용을 위한 1일경구투여량은 50~2000mg이고, 바람직하게는 600~1000mg이다.The daily oral dose for the anti-inflammatory analgesic effect of the compound of the present invention is 50-2000 mg, preferably 600-1000 mg.
본 발명의 목적화합물들은 약리학적으로 시험한 결과 적당하거나 거의 무시할 정도의 독성을 나타냈다. 본 발명의 세가지 화합물들은 모두 새앙쥐에 경구 투여한 결과 1220mg/kg 이상의 LD50치를 나타냈으며, 에토돌산 1113mg/kg(문헌기재 1141mg/kg)과 비교할 때 그 독성이 현저히 저하되었음을 보인다. 새앙쥐의 급성독성실험 데이터를 에토돌산과 비교하여 표2에 나타내었다.The target compounds of the present invention showed moderate or almost negligible toxicity when tested pharmacologically. All three compounds of the present invention showed an LD 50 value of 1220 mg / kg or more as a result of oral administration to a rat, and its toxicity was markedly reduced compared to 1113 mg / kg of etodol acid (1141 mg / kg of literature). The acute toxicity test data of young rats are shown in Table 2 in comparison with etodolic acid.
[표 2]TABLE 2
새앙쥐에 있어서 경구적으로 투여한 에토돌산알루미늄과 에토돌산의 급성독성* In saeangjwi acute toxicity of etoposide and etoposide Dolsan aluminum Dolsan administered orally *
이하 실시예를 들어 본 발명을 구체적으로 설명하고자 한다.Hereinafter, the present invention will be described in detail with reference to Examples.
[실시예 1]Example 1
에토돌산의 알루미늄염(1:1) ;Aluminum salt of etodol acid (1: 1);
1,8-디에칠-1,3,4,9-테트라하이드로피라노[3,4-b]인돌-1-아세트산 디하이드로 옥시 알루미늄 에토돌산 11.48g(0.04M)을 물 80ml에 현탁시키고, 여기에 1N-NaOH 용액 40ml(0.04M)을 교반하면서 첨가하여 용해시킨다. 따로 물 120ml에 Al(NO3)3·9H2O 15.0g(0.04)을 용해시킨 용액을 만든다. 이들 두 액을 220ml의 물에 NaHCO36.72g(0.08M)을 용해시킨 용액에 교반하면서 동시에 적가하여 반응시킨다. 침전이 즉시 생기는데, 약 10분간 방치한 다음 1시간 교반하고 여취한 다음 물로 씻고, 고형물을 105℃에서 건조한다. 이는 백색 분말로 물에 불용이고, 톨루엔, 벤젠, 알콜류등 대부분의 유기용제에 가요성이다.11.48 g (0.04 M) of 1,8-dimethyl-1,3,4,9-tetrahydropyrano [3,4-b] indole-1-acetic acid dihydrooxy aluminum etodolic acid was suspended in 80 ml of water, 40 ml (0.04 M) of 1N-NaOH solution was added thereto while stirring to dissolve. Separately, 15.0 g (0.04) of Al (NO 3 ) 3 .9H 2 O was dissolved in 120 ml of water. These two liquids are added dropwise to the solution in which 6.72 g (0.08 M) of NaHCO 3 is dissolved in 220 ml of water, and stirred at the same time. Precipitation occurs immediately, which is left for about 10 minutes, stirred for 1 hour, filtered, washed with water, and the solid is dried at 105 ° C. It is a white powder, insoluble in water and flexible to most organic solvents such as toluene, benzene and alcohols.
수득량 : 14.8g(이론치 14.9g)Yield: 14.8 g (14.9 g of theory)
융점 : 218~221℃Melting Point: 218 ~ 221 ℃
원소분석 : C17H20NO3Al(OH)2로서Elemental Analysis: As C 17 H 20 NO 3 Al (OH) 2
이론치(%) : C ; 58.78, H ; 6.38, N ; 4.03, Al ; 7.77Theoretical value (%): C; 58.78, H; 6.38, N; 4.03, Al; 7.77
분석치(수분에 대한 보정치%):C ; 58.55, H ; 6.30, N ; 3.88, Al ; 7.85(회분), 7.30(EDTA), 7.58(평균)Analytical value (% correction for moisture): C; 58.55, H; 6.30, N; 3.88, Al; 7.85 (batch), 7.30 (EDTA), 7.58 (average)
함수율[칼-횟샤법] : 3.50%Moisture Content [Knife-Shansha Method]: 3.50%
적외부 흡수 스펙트럼[IR(KBr)cm-1] : 3420(-OH,=NH), 1594(-COO-)Infrared absorption spectrum [IR (KBr) cm -1 ]: 3420 (-OH, = NH), 1594 (-COO-)
핵자기 공명 스펙트럼[1H-NMR(300MHz,CDCl3] δ:0.8(3H,t,C1-CH2 CH3), 0.8(3H,t,C8-CH2 ), 2.0~2.2(2H,m,C1-CH3), 2.8~2.9(4H,m,C3-H2,C4-H2), 3.0(2H,S,-COO-), 4.0~4.1(2H,m,C8-CH3), 7.0~7.1(2H,m,C5-H,C6-H), 7.2(1H,s,-OH), 7.3(1H,d,C7-H), 8.6(1H,s,=NH)Nuclear Magnetic Resonance Spectrum [ 1 H-NMR (300MHz, CDCl 3 ] δ: 0.8 (3H, t, C 1 -CH 2 CH 3 ), 0.8 (3H, t, C 8 -CH 2 ), 2.0 to 2.2 (2H, m, C 1- CH 3 ), 2.8 ~ 2.9 (4H, m, C 3 -H 2 , C 4 -H 2 ), 3.0 (2H, S,- COO-), 4.0 ~ 4.1 (2H, m, C 8- CH 3 ), 7.0 ~ 7.1 (2H, m, C 5 -H, C 6 -H), 7.2 (1H, s, -OH), 7.3 (1H, d, C 7 -H), 8.6 (1H, s , = NH)
[실시예 2]Example 2
에토돌산의 알루미늄염(2:1) ;Aluminum salt of etodol acid (2: 1);
디[1,8-디에칠-1,3,4,9-테트라하이드로피라노[3,4-b]인돌-1-아세트산]모노하이드로옥시 알루미늄 에토돌산 14.35g(0.05M)을 물 30ml에 현탁시키고, 여기서 1N-NaOH 용액 50ml(0.05M)을 충분히 교반하면서 첨가하여 용해시킨다. 따로 물 30ml에 Al(NO3·9H2O 9.08g(0.242M)을 용해시킨 용액을 만들고, 이들 두 액을 25ml의 물에 NaHCO32.10g(0.025M)을 용해시킨 용액에 교반하면서 동시에 적가하면 침전이 즉시 생성되며 이를 1시간 교반한 다음 고형물을 여취하여 물로 씻고 105℃에서 건조한다.14.35 g (0.05 M) of di [1,8-diech-1,3,4,9-tetrahydropyrano [3,4-b] indole-1-acetic acid] monohydrooxy aluminum etodolic acid in 30 ml of water Suspension, where 50 ml (0.05 M) of 1N-NaOH solution is added with sufficient stirring to dissolve. Separately, a solution of 9.08 g (0.242 M) of Al (NO 3 · 9H 2 O) was dissolved in 30 ml of water, and these two solutions were added dropwise while stirring to a solution of 2.10 g (0.025 M) of NaHCO 3 dissolved in 25 ml of water. Precipitation immediately occurs, and after stirring for 1 hour, the solids are filtered off, washed with water and dried at 105 ° C.
이는 백색 분말로 물에 불용이고, 톨루엔, 벤젠, 알콜류등 대부분의 유기용제에 가용성이다.It is a white powder, insoluble in water and soluble in most organic solvents such as toluene, benzene and alcohols.
수득량 : 14.6g(이론치 14.9g)Yield: 14.6 g (14.9 g of theory)
융 점 : 211~213℃Melting Point: 211 ~ 213 ℃
원소분석 : (C17H20NO3)2Al(OH)로서Elemental analysis: as (C 17 H 20 NO 3 ) 2 Al (OH)
이론치(%) : C ; 66.22, H ; 6.70, N ; 4.50, Al ; 4.38Theoretical value (%): C; 66.22, H; 6.70, N; 4.50, Al; 4.38
분석치(수분에 대한 보정치%) : C ; 65.43, H ; 6.71, N ; 4.41, Al ; 4.73(회분), 4.00(EDTA), 4.37(평균)Analytical value (% correction for moisture): C; 65.43, H; 6.71, N; 4.41, Al; 4.73 (Batch), 4.00 (EDTA), 4.37 (Average)
함수율[칼-횟샤법] : 3.10%Moisture Content [Knife-Shansha Method]: 3.10%
적외부 흡수 스펙트럼[IR(KBr)cm-1] : 3420(-OH,=NH), 1594(-COO-)Infrared absorption spectrum [IR (KBr) cm -1 ]: 3420 (-OH, = NH), 1594 (-COO-)
핵자기 공명 스펙트럼[1H-NMR(300MHz,CDCl3] δ:0.8(3H,t,C1-CH2 ), 1.3(3H,t,C8-CH2 ), 2.0~2.2(2H,m,C1-CH3), 2.8~2.9(4H,m,C3-H2,C4-H2), 3.0(2H,S,-COO-), 4.0~4.1(2H,m,C8-CH3), 7.0~7.1(2H,m,C5-H,C6-H), 7.2(1H,s,-OH), 7.3(1H,d,-C7-H), 8.6(1H,s,=NH)Nuclear Magnetic Resonance Spectrum [ 1 H-NMR (300MHz, CDCl 3 ] δ: 0.8 (3H, t, C 1 -CH 2 ), 1.3 (3H, t, C 8 -CH 2 ), 2.0 to 2.2 (2H, m, C 1- CH 3 ), 2.8 ~ 2.9 (4H, m, C 3 -H 2 , C 4 -H 2 ), 3.0 (2H, S,- COO-), 4.0 ~ 4.1 (2H, m, C 8- CH 3 ), 7.0 to 7.1 (2H, m, C 5 -H, C 6 -H), 7.2 (1H, s, -OH), 7.3 (1H, d, -C 7 -H), 8.6 (1H, s, = NH)
[실시예 3]Example 3
에토돌산의 알루미늄염(3 : 1) ;Aluminum salt of etodolic acid (3: 1);
트리[1,8-디에칠-1,3,4,9-테트라하이드로피라노[3,4-b]인돌-1-아세트산]알루미늄Tri [1,8-Diethyl-1,3,4,9-tetrahydropyrano [3,4-b] indole-1-acetic acid] aluminum
에토돌산 17.24g(0.06M)을 물 83ml에 현탁시키고, 여기에 1N-NaOH 용액 62ml(0.062M)을 충분히 교반하면서 첨가하여 용해시킨다. 따로 물 90ml에 Al(NO3)3·9H2O 22.54g(0.06M)을 용해시킨 용액을 만들고, 이를 전기 에토돌산나트륨염 용액에 충분히 교반하면서 적가하여 반응시키고, 더욱 1시간 교반하여 반응을 완결시키고, 여과하여 물로 씻고, 고형물을 105℃에서 건조한다. 이는 대황백색 분말로 물에 불용이고, 톨루엔, 벤젠, 알콜류등 대부분의 유기용제에 이용성이다.17.24 g (0.06 M) of etodol acid are suspended in 83 ml of water, and 62 ml (0.062 M) of 1N-NaOH solution is added thereto with sufficient stirring to dissolve. Separately, a solution of 22.54 g (0.06 M) of Al (NO 3 ) 3 .9H 2 O was dissolved in 90 ml of water, which was then added dropwise to the sodium etodol acid salt solution with sufficient stirring, followed by further stirring for 1 hour. Complete, filter, wash with water and solids are dried at 105 ° C. It is a rhubarb white powder, insoluble in water, and soluble in most organic solvents such as toluene, benzene, and alcohols.
수득량 : 17.4g(이론치 17.7g)Yield: 17.4 g (17.7 g of theory)
융 점 : 181~185℃Melting Point: 181 ~ 185 ℃
원소분석 : (C17H20NO3)Al로서Elemental Analysis: As (C 17 H 20 NO 3 ) Al
이론치(%) : C ; 69.13, H ; 6.82, N ; 4.74, Al ; 3.05Theoretical value (%): C; 69.13, H; 6.82, N; 4.74, Al; 3.05
분석치(수분에 대한 보정치%): C ; 68.74, H ; 7.07, N ; 4.63, Al ; 3.25(회분), 2.90(EDTA), 3.08(평균)Analytical value (% correction for moisture): C; 68.74, H; 7.07, N; 4.63, Al; 3.25 (ash), 2.90 (EDTA), 3.08 (average)
함수율[칼-횟샤법]:1.80%Moisture Content [Knife-Shitsha Method]: 1.80%
적외부 흡수 스펙트럼[IR(KBr)cm-1] : 3420(-OH,=NH), 1594(-COO-)Infrared absorption spectrum [IR (KBr) cm -1 ]: 3420 (-OH, = NH), 1594 (-COO-)
핵자기 공명 스펙트럼[1H-NMR(300MHz,CDCl3] δ:0.8(3H,t,C1-CH2 ), 1.3(3H,t,C8-CH2 ), 2.0~2.2(2H,m,C1-CH3), 2.8~2.9(4H,m,C3-H,C4-H2), 3.0(2H,S,-COO-), 4.0~4.1(2H,m,C8-CH3), 7.0~.1(2H,m,C5-H,C6-H), 7.3(1H,d,C7-H), 8.6(1H,s,=NH)Nuclear Magnetic Resonance Spectrum [ 1 H-NMR (300MHz, CDCl 3 ] δ: 0.8 (3H, t, C 1 -CH 2 ), 1.3 (3H, t, C 8 -CH 2 ), 2.0 to 2.2 (2H, m, C 1- CH 3 ), 2.8 ~ 2.9 (4H, m, C 3 -H, C 4 -H 2 ), 3.0 (2H, S,- COO-), 4.0 ~ 4.1 (2H, m, C 8- CH 3 ), 7.0 ~ .1 (2H, m, C 5 -H, C 6 -H), 7.3 (1H, d, C 7 -H), 8.6 (1H, s, = NH)
[실시예 4]Example 4
에토돌산의 알루미늄염(3 : 1) ;Aluminum salt of etodolic acid (3: 1);
트리[1,8-디에칠-1,3,4,9-테트라하이드로피라노[3,4-b]인돌-1-아세트산]알루미늄Tri [1,8-Diethyl-1,3,4,9-tetrahydropyrano [3,4-b] indole-1-acetic acid] aluminum
에토돌산 8.62g(0.03M)을 물 42ml에 현탁시키고, 여기에 1N-NaOH 용액 31ml(0.031M)을 교반하면서 첨가하여 용해시킨다. 따로 물 45ml에 AlCl34.0g(0.03M)을 용해시킨 용액을 만들고, 이를 전기에토돌산나트륨염용액에 충분히 교반하면서 적가하여 반응시키고, 더욱 1시간 교반하여 반응을 완결시키고, 여취하여 물로 씻고, 고형물을 105℃에서 건조한다. 이는 대황백색 분말로 물에 불용이고, 톨루엔, 벤젠, 알콜류등 대부분의 유기용제에 이용성이다.8.62 g (0.03 M) of etodol acid is suspended in 42 ml of water, and 31 ml (0.031 M) of 1N-NaOH solution is added thereto while stirring to dissolve. Separately, a solution of 4.0 g (0.03 M) of AlCl 3 was dissolved in 45 ml of water, which was then added dropwise to an aqueous sodium electrotodolic acid solution with sufficient stirring, followed by further stirring for 1 hour to complete the reaction, filtered and washed with water. The solid is dried at 105 ° C. It is a rhubarb white powder, insoluble in water, and soluble in most organic solvents such as toluene, benzene, and alcohols.
수득량 : 8.1g(이론치 8.9g)Yield: 8.1 g (8.9 g of theory)
융 점 : 180~183℃Melting Point: 180 ~ 183 ℃
원소분석 : (C17H20NO3)3Al로서Elemental analysis: as (C 17 H 20 NO 3 ) 3 Al
이론치(%) : Al ; 3.05Theoretical value (%): Al; 3.05
분석치(수분에 대한 보정치%) : Al ; 3.29(회분), 3.07(EDTA), 3.08(평균)Analytical value (% of correction value for moisture): Al; 3.29 (batch), 3.07 (EDTA), 3.08 (average)
함수율[칼-횟샤법]:2.10%Moisture Content [Knife-Shansha Method]: 2.10%
[실시예 5]Example 5
에토돌산의 알루미늄염(2 : 1) ;Aluminum salt of etodol acid (2: 1);
디[1,8-디에칠-1,3,4,9-테트라 하이드로피라도[3,4-b]인돌-1-아세트산]모노하이드로옥시 알루미늄 알루미늄 이소프로폭싸이드 10.2g(0.05M)을 건조 이소프로파놀 80ml에 용해시켜, 에토돌산 28.7g(0.1M)을 역시 이소프로파놀 80ml에 용해시킨 액에 교반하면서 적가하고, 더욱 1시간 교반한 다음 물 5ml를 가하고, 1야 방치한 다음 반응액으로부터 이소프로파놀 및 물을 갑압류거한다. 잔류물을 에타놀 50ml에 용해시키고 동 용적의 물을 가하여 석출하는 침전물을 물로 씻은 다음 105℃에서 건조한다.10.2 g (0.05 M) of di [1,8-diech-1,3,4,9-tetra hydropyrido [3,4-b] indole-1-acetic acid] monohydrooxy aluminum aluminum isopropoxide It was dissolved in 80 ml of dry isopropanol, and 28.7 g (0.1 M) of etodol acid was also added dropwise with stirring to 80 ml of isopropanol. After stirring for 1 hour, 5 ml of water was added, and the mixture was left to stand for 1 night. Isopropanol and water are depressurized from the liquid. The residue is dissolved in 50 ml of ethanol, and the precipitate precipitated by adding the same volume of water is washed with water and dried at 105 ° C.
수득량 : 30.0g(이론치 30.7g)Yield: 30.0 g (30.7 g of theory)
융 점 : 210~212℃Melting Point: 210 ~ 212 ℃
원소분석 : (C17H20NO3)2Al(OH)로서Elemental analysis: as (C 17 H 20 NO 3 ) 2 Al (OH)
이론치(%) : Al ; 4.38Theoretical value (%): Al; 4.38
분석치(수분에 대한 보정치%): Al ; 4.80(회분), 4.36(EDTA), 4.58(평균)Analytical value (% correction for moisture): Al; 4.80 (ash), 4.36 (EDTA), 4.58 (average)
함수율[칼-횟샤법] : 3.0%Moisture Content [Knife-Shansha Method]: 3.0%
Claims (8)
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| KR1019930005977A KR950013576B1 (en) | 1993-04-09 | 1993-04-09 | Pyranoindoles acetic aluminium compound and process for preparing the same |
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| KR1019930005977A KR950013576B1 (en) | 1993-04-09 | 1993-04-09 | Pyranoindoles acetic aluminium compound and process for preparing the same |
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| KR950013576B1 true KR950013576B1 (en) | 1995-11-09 |
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