JPS6147840B2 - - Google Patents
Info
- Publication number
- JPS6147840B2 JPS6147840B2 JP12235779A JP12235779A JPS6147840B2 JP S6147840 B2 JPS6147840 B2 JP S6147840B2 JP 12235779 A JP12235779 A JP 12235779A JP 12235779 A JP12235779 A JP 12235779A JP S6147840 B2 JPS6147840 B2 JP S6147840B2
- Authority
- JP
- Japan
- Prior art keywords
- cysteine
- gold
- methylpropanoyl
- sodium
- compound
- 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
- 239000004201 L-cysteine Substances 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 150000001875 compounds Chemical class 0.000 description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 239000010931 gold Substances 0.000 description 6
- 229910052737 gold Inorganic materials 0.000 description 6
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- 208000025747 Rheumatic disease Diseases 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- VUAFHZCUKUDDBC-BYPYZUCNSA-N Bucillamine Chemical compound CC(C)(S)C(=O)N[C@@H](CS)C(O)=O VUAFHZCUKUDDBC-BYPYZUCNSA-N 0.000 description 2
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 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
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 150000002344 gold compounds Chemical class 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- DTNJZLDXJJGKCM-UHFFFAOYSA-K sodium;trichlorogold Chemical compound [Na].Cl[Au](Cl)Cl DTNJZLDXJJGKCM-UHFFFAOYSA-K 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 235000013878 L-cysteine Nutrition 0.000 description 1
- CHZXKDFOXLOZMI-UHFFFAOYSA-N S-(1-chloro-2-methyl-1-oxopropan-2-yl) benzenecarbothioate Chemical compound C(C1=CC=CC=C1)(=O)SC(C(=O)Cl)(C)C CHZXKDFOXLOZMI-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- -1 ferrous gold halide Chemical class 0.000 description 1
- IZLAVFWQHMDDGK-UHFFFAOYSA-N gold(1+);cyanide Chemical compound [Au+].N#[C-] IZLAVFWQHMDDGK-UHFFFAOYSA-N 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- VMDSWYDTKFSTQH-UHFFFAOYSA-N sodium;gold(1+);dicyanide Chemical compound [Na+].[Au+].N#[C-].N#[C-] VMDSWYDTKFSTQH-UHFFFAOYSA-N 0.000 description 1
- AGHLUVOCTHWMJV-UHFFFAOYSA-J sodium;gold(3+);2-sulfanylbutanedioate Chemical compound [Na+].[Au+3].[O-]C(=O)CC(S)C([O-])=O.[O-]C(=O)CC(S)C([O-])=O AGHLUVOCTHWMJV-UHFFFAOYSA-J 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
Description
【発明の詳細な説明】
本発明は式〔〕
で示されリウマチ疾患治療効果を有するＳ―オ―
ロ―Ｎ―（２―オ―ロチオ―２―メチルプロパノ
イル）―Ｌ―システインおよびその塩類に関す
る。金化合物がリウマチ疾患治療薬として有効で
あることは広く知られており、例えば金チオリン
ゴ酸ナトリウムのような化合物が使用されてい
る。一方、Ｎ―（２―メルカプト―２―メチルプ
ロパノイル）―Ｌ―システインがリウマチ疾患に
有効であることが明らかにされており（特願昭53
―125537）、その金化合物である本発明化合物
〔〕は、リウマチ疾患治療薬としての効果を有
するものである。[Detailed Description of the Invention] The present invention is based on the formula [] S-O-, which has a therapeutic effect on rheumatic diseases
This invention relates to rho-N-(2-o-rothio-2-methylpropanoyl)-L-cysteine and its salts. It is widely known that gold compounds are effective as therapeutic agents for rheumatic diseases, and compounds such as sodium gold thiomalate are used, for example. On the other hand, it has been revealed that N-(2-mercapto-2-methylpropanoyl)-L-cysteine is effective against rheumatoid diseases (Japanese Patent Application No. 1983).
-125537), and its gold compound, the compound of the present invention [], is effective as a therapeutic agent for rheumatic diseases.
本発明化合物〔〕は、例えば次のＡ，Ｂのよ
うな方法で合成される。 The compound of the present invention [] can be synthesized, for example, by the following methods A and B.
Ａ
式〔〕で示される化合物とシアン化第一金、
シアン化金ナトリウム、ハロゲン化第一金のよう
な一価の金と反応させるか、還元剤、例えば亜硫
酸ガスの存在下、塩化金酸、塩化金ナトリウムの
ような三価の金を反応させるかまたは、例えばジ
メチルスルフイドのようなスルフイド化合物と三
価の金を反応させ得られる化合物（米国特許
2984575号）に、式〔〕で示される化合物を作
用させて得ることができる。A A compound represented by the formula [] and primary gold cyanide,
Either by reacting with monovalent gold such as sodium gold cyanide or ferrous gold halide, or by reacting with trivalent gold such as chloroauric acid or sodium gold chloride in the presence of a reducing agent such as sulfur dioxide gas. Alternatively, compounds obtained by reacting trivalent gold with sulfide compounds, such as dimethyl sulfide (U.S. Pat.
2984575) with a compound represented by the formula [].
Ｂ 一般式〔〕
〔式中、Ｘはハロゲン原子、Ｒはベンゾイル基
ままたはアセチル基を示す〕で示される化合物と
Ｓ―オ―ロ―Ｌ―システインを反応させ、一般式
〔〕
〔式中、Ｒは前記と同義。〕で表わされる化合
物を得、次いで、水酸化ナトリウム、アンモニア
などのアルカリ処理をし式〔〕で示される化合
物を得る。B General formula [] A compound represented by the formula [wherein X is a halogen atom and R represents a benzoyl group or an acetyl group] is reacted with S-o-rho-L-cysteine to form a compound of the general formula [] [In the formula, R has the same meaning as above. ] is obtained, and then treated with an alkali such as sodium hydroxide or ammonia to obtain a compound represented by the formula [].
続いて〔〕で示される化合物をＡに示した方
法で処理して、本発明化合物〔〕を得る。 Subsequently, the compound represented by [ ] is treated by the method shown in A to obtain the compound of the present invention [ ].
以下に実施例を示す。 Examples are shown below.
実施例 １
Ｓ―オ―ロ―Ｎ―（２―オ―ロチオ―２―メチ
ルプロパノイル）―Ｌ―システインの製造
Ｎ―（２―メルカプト―２―メチルプロパノ
イル）―Ｌ―システイン6.2ｇを濃アンモニア
水100mlに溶解し、シアン化第一金12.3ｇを加
え室温で１時間攪拌する。過剰のアンモニアを
減圧留去した後、希塩酸で酸性とし得られる沈
殿を取して標記化合物14.8ｇ（収率87％）を
得る。Example 1 Production of S-o-ro-N-(2-o-rothio-2-methylpropanoyl)-L-cysteine 6.2 g of N-(2-mercapto-2-methylpropanoyl)-L-cysteine Dissolve in 100 ml of concentrated ammonia water, add 12.3 g of ferrous cyanide, and stir at room temperature for 1 hour. After excess ammonia was distilled off under reduced pressure, the mixture was acidified with dilute hydrochloric acid and the resulting precipitate was collected to obtain 14.8 g (yield: 87%) of the title compound.
融点218〜229℃（分解）
〔α２５ Ｄ＋436.6゜
（ｃ＝0.3，0.1N水酸化ナトリウム）
金含有量63.5％（計算値64.0％）
Ｎ―（２―メルカプト―２―メチルプロパノ
イル）―Ｌ―システイン3.2ｇをＮ水酸化ナト
リウム15mlに溶解し、氷冷下攪拌しながら亜硫
酸ガスを吹き込む。塩化金ナトリウム1.9ｇの
水10ml溶液を滴下し、滴下終了後室温で更に30
分間攪拌した後、沈殿を取して標記化合物
1.7ｇ（収率58％）を得る。 Melting point 218-229℃ (decomposed) [α 25 D +436.6゜ (c=0.3, 0.1N sodium hydroxide) Gold content 63.5% (calculated value 64.0%) N-(2-mercapto-2-methylpropanoyl ) - Dissolve 3.2 g of L-cysteine in 15 ml of N sodium hydroxide, and blow in sulfur dioxide gas while stirring under ice cooling. A solution of 1.9 g of sodium gold chloride in 10 ml of water was added dropwise, and after the dropwise addition was completed, the mixture was further heated at room temperature for 30 ml.
After stirring for a minute, remove the precipitate and extract the title compound.
Obtain 1.7 g (58% yield).
Ｓ―オ―ロ―Ｌ―システイン0.32ｇを0.1N水
酸化ナトリウム10mlに溶解し、炭酸ナトリウム
1.0ｇを加える。氷冷下攪拌しながら、Ｓ―ベ
ンゾイル―２―メルカプト―２―メチルプロパ
ノイルクロリド0.29ｇを滴下する。滴下終了後
室温でさらに１時間攪拌した後、沈殿を取し
てＳ―オ―ロ―Ｎ―（Ｓ―ベンゾイル―２―メ
ルカプト―２―メチルプロパノイル）―Ｌ―シ
ステインナトリウム0.32ｇ（収率59％、融点
205〜210℃（分解））を得る。次に、Ｓ―オ―
ロ―Ｎ―（Ｓ―ベンゾイル―２―メルカプト―
２―メチルプロパノイル）―Ｌ―システインナ
トリウム0.32ｇを濃アンモニア水10mlに入れ、
次いでシアン化第一金0.13ｇを加え室温で一夜
攪拌する。過剰のアンモニアを減圧留去した
後、希塩酸で酸性とし沈殿を取して標記化合
物0.24ｇ（収率66％）を得る。 Dissolve 0.32 g of S-O-R-L-cysteine in 10 ml of 0.1N sodium hydroxide, and add sodium carbonate.
Add 1.0g. While stirring under ice-cooling, 0.29 g of S-benzoyl-2-mercapto-2-methylpropanoyl chloride is added dropwise. After the addition was completed, the mixture was further stirred at room temperature for 1 hour, and the precipitate was collected to give 0.32 g of sodium S-oro-N-(S-benzoyl-2-mercapto-2-methylpropanoyl)-L-cysteine (yield 59%, melting point
205-210℃ (decomposition)). Next, S-o-
Rho-N-(S-benzoyl-2-mercapto-
Add 0.32 g of sodium 2-methylpropanoyl)-L-cysteine to 10 ml of concentrated ammonia water,
Next, 0.13 g of ferrous cyanide was added and stirred overnight at room temperature. After excess ammonia was distilled off under reduced pressure, the mixture was acidified with dilute hydrochloric acid and the precipitate was collected to obtain 0.24 g (yield: 66%) of the title compound.
実施例 ２
Ｓ―オ―ロ―Ｎ―（２―オ―ロチオ―２―メチ
ルプロパノイル）―Ｌ―システインナトリウム
の製造
Ｓ―オ―ロ―Ｎ―（２―オ―ロチオ―２―メチ
ルプロパノイル）―Ｌ―システイン11.0ｇを0.2N
水酸化ナトリウム200mlに溶解した後、エタノー
ル600mlを加え得られる沈殿を取して標記化合
物9.9ｇ（収率87％）を得る。Example 2 Production of S-o-rho-N-(2-o-rothio-2-methylpropanoyl)-L-cysteine sodium Noil)-L-cysteine 11.0g 0.2N
After dissolving in 200 ml of sodium hydroxide, 600 ml of ethanol was added and the resulting precipitate was collected to obtain 9.9 g (yield: 87%) of the title compound.
融点243〜247℃（分解） 〔α〕２５ Ｄ＋396.0゜（ｃ＝0.2，水） 金含有量61.5％（計算値61.8％） Melting point 243-247℃ (decomposition) [α] 25 D +396.0゜ (c=0.2, water) Gold content 61.5% (calculated value 61.8%)
Claims (1)
オ―ロチオ―２―メチルプロパノイル）―Ｌ―シ
ステインおよびその塩類。 [Claims] 1 S-Auro-N-(2-
(orothio-2-methylpropanoyl)-L-cysteine and its salts.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12235779A JPS5645487A (en) | 1979-09-22 | 1979-09-22 | Antirheumatic |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12235779A JPS5645487A (en) | 1979-09-22 | 1979-09-22 | Antirheumatic |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5645487A JPS5645487A (en) | 1981-04-25 |
| JPS6147840B2 true JPS6147840B2 (en) | 1986-10-21 |
Family
ID=14833894
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP12235779A Granted JPS5645487A (en) | 1979-09-22 | 1979-09-22 | Antirheumatic |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5645487A (en) |
-
1979
- 1979-09-22 JP JP12235779A patent/JPS5645487A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5645487A (en) | 1981-04-25 |
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