JPH0380156B2 - - Google Patents
Info
- Publication number
- JPH0380156B2 JPH0380156B2 JP25888884A JP25888884A JPH0380156B2 JP H0380156 B2 JPH0380156 B2 JP H0380156B2 JP 25888884 A JP25888884 A JP 25888884A JP 25888884 A JP25888884 A JP 25888884A JP H0380156 B2 JPH0380156 B2 JP H0380156B2
- Authority
- JP
- Japan
- Prior art keywords
- carbon atoms
- dithiol
- general formula
- reaction
- compounds
- 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
- IVJFXSLMUSQZMC-UHFFFAOYSA-N 1,3-dithiole Chemical class C1SC=CS1 IVJFXSLMUSQZMC-UHFFFAOYSA-N 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- FAUNYRAJFMUZJQ-UHFFFAOYSA-M 1,3-dithiol-2-ylidene(methyl)sulfanium;iodide Chemical compound [I-].CSC=1SC=C[S+]=1 FAUNYRAJFMUZJQ-UHFFFAOYSA-M 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 208000019423 liver disease Diseases 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
（産業上の利用分野）
本発明は新規な１，３−ジチオール誘導体に関
する。
（従来の技術）
一般式
で表わされる１，３−ジチオール誘導体におい
て、Ｒが低級アルキル基である１，３−ジチオー
ル化合物は、例えば特公昭49−35272，特開昭51
−144734及び特開昭52−83751等に記載された公
知化合物である。これら公知の１，３−ジチオー
ル化合物は肝疾患用剤として有効であることが報
告されているが、その問題点として胃腸障害が現
われることがある。
（発明が解決しようとする問題点）
本発明の目的はより優れた肝疾患治療効果を有
し、更に副作用の胃腸障害が軽減された新規な
１，３−ジチオール誘導体を提供することにあ
る。
（問題点を解決するための手段）
本発明は一般式
（式中R1，R2は同一又は異なつて水素、炭素
数１〜５のアルキル基、フエニル基又は互いに結
合して隣接炭素原子と共に炭素数５〜６のシクロ
アルキル基を示す）で表わされる１，３−ジチオ
ール誘導体に係る。
一般式(1)中、R1，R2で表わされる炭素数１〜
５のアルキル基としてはメチル、エチル、プロピ
ル、イソプロピル、ブチル、sec−ブチル、tert
−ブチル、ペンチル基などを例示できる。また炭
素数５〜６のシクロアルキル基は、シクロペンチ
ル及びシクロヘキシルである。
本発明の上記一般式(1)で示される１，３−ジチ
オール誘導体は文献未載の新規化合物であり、肝
疾患用剤として有用である。
本発明の一般式(1)で示される１，３−ジチオー
ル誘導体は、例えば以下の方法により製造され
る。溶媒中、水素化カルシウム、リチウムジイソ
プロピルアミン、水素化ナトリウム等の塩基の存
在下、一般式(2)で示される化合物に、２−メチル
チオ−１，３−ジチオリウムアイオダイド(3)を作
用させる方法で、次の反応式で表わされる。
（式中R1，R2は前記と同じ）
反応に使用される溶媒としては、ジメチルホル
ムアミド、ジメチルアセトアミドやベンゼン、ト
ルエン等の炭化水素類、テトラハイドロフラン、
１，２−ジメトキシエタン等のエーテル類等が使
用可能であるが、テトラハイドロフラン、１，２
−ジメトキシエタン等のエーテル類が好適に使用
される。塩基は水素化カルシウム、水素化ナトリ
ウムが好適に使用される。また、化合物(2)と(3)の
使用割合は(2)に対して(3)を１〜1.5倍当量使用し
ても良いが、等量使用が有利である。反応温度も
適宜選択すればよいが一般に０℃〜室温程度で行
なうのが有利である。
尚、本反応において出発原料として用いられる
化合物(2)は文献既知の化合物であり、例えば、
Chem.Ber.，94，929（1961）やEur.J.Med.Chim，
Ther.，11，415（1976）などに報告されている。
上記方法により得られた本発明化合物(1)の単離
精製は、例えば抽出、再結晶、カラムクロマトグ
ラフイー等の通常の操作によつて行なわれる。
以下本発明の１，３−ジチオール誘導体の合成
例を実施例として説明する。
実施例 １
乾燥テトラハイドロフラン（15ml）に50％水素
化ナトリウム（0.8ｇ）を加え氷冷下、２，２−
ペンタメチレン−１，３−ジオキサン−４，６−
ジオン3.0ｇを徐々に加える。この温度で15分、
室温で30分撹拌を行ない、再び氷冷し２−メチル
チオ−１，３−ジチオリウムアイオダイド4.7ｇ
を加える。次に室温で15時間撹拌する。反応後、
反応液を氷水100mlに注ぎ、析出した結晶をロ取、
エーテルにて洗浄する。粗結晶をジクロロメタン
−メタノールより再結晶し、mp245〜246℃の結
晶として、５−（１，３−ジチオール−２−イリ
デン）−２，２−ペンタメチレン−１，３−ジオ
キサン−４，６−ジオン（化合物１）を3.6ｇ
（78％）得た。尚、元素分析、1H−NMR（プロト
ン核磁気共鳴）を第１表に示す。
実施例 ２〜６
実施例１と同様の操作により化合物２〜６を合
成した。尚、化合物２〜６の物理恒数を第１表に
示す。元素分析において(C)は計算値、(F)は分析値
を示す。
(Industrial Application Field) The present invention relates to a novel 1,3-dithiol derivative. (Prior art) General formula Among the 1,3-dithiol derivatives represented by R, the 1,3-dithiol compounds in which R is a lower alkyl group are disclosed, for example, in Japanese Patent Publication No. 49-35272,
-144734 and JP-A-52-83751, etc., are known compounds. Although these known 1,3-dithiol compounds are reported to be effective as agents for liver diseases, their problem is that they may cause gastrointestinal disorders. (Problems to be Solved by the Invention) An object of the present invention is to provide a novel 1,3-dithiol derivative that has a better therapeutic effect on liver diseases and has reduced side effects of gastrointestinal disorders. (Means for solving the problems) The present invention is based on the general formula (In the formula, R 1 and R 2 are the same or different and represent hydrogen, an alkyl group having 1 to 5 carbon atoms, a phenyl group, or a cycloalkyl group having 5 to 6 carbon atoms bonded together with adjacent carbon atoms) It concerns a 1,3-dithiol derivative. In general formula (1), the number of carbon atoms represented by R 1 and R 2 is from 1 to
The alkyl group of 5 is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert
Examples include -butyl and pentyl groups. Further, the cycloalkyl group having 5 to 6 carbon atoms is cyclopentyl and cyclohexyl. The 1,3-dithiol derivative of the present invention represented by the above general formula (1) is a novel compound that has not been described in any literature, and is useful as a drug for liver diseases. The 1,3-dithiol derivative represented by the general formula (1) of the present invention is produced, for example, by the following method. 2-methylthio-1,3-dithiolium iodide (3) is allowed to act on the compound represented by general formula (2) in a solvent in the presence of a base such as calcium hydride, lithium diisopropylamine, or sodium hydride. This method is expressed by the following reaction formula. (In the formula, R 1 and R 2 are the same as above.) Examples of the solvent used in the reaction include dimethylformamide, dimethylacetamide, benzene, hydrocarbons such as toluene, tetrahydrofuran,
Ethers such as 1,2-dimethoxyethane can be used, but tetrahydrofuran, 1,2
- Ethers such as dimethoxyethane are preferably used. Calcium hydride and sodium hydride are preferably used as the base. Furthermore, the ratio of compounds (2) and (3) to be used may be 1 to 1.5 times the equivalent of (2), but it is advantageous to use the same amount. Although the reaction temperature may be selected appropriately, it is generally advantageous to carry out the reaction at a temperature of about 0°C to room temperature. The compound (2) used as a starting material in this reaction is a compound known in the literature, for example,
Chem.Ber., 94 , 929 (1961) and Eur.J.Med.Chim,
Ther., 11 , 415 (1976), etc. Isolation and purification of the compound (1) of the present invention obtained by the above method is carried out by conventional operations such as extraction, recrystallization, column chromatography, and the like. Examples of the synthesis of 1,3-dithiol derivatives of the present invention will be explained below as examples. Example 1 50% sodium hydride (0.8 g) was added to dry tetrahydrofuran (15 ml) and 2,2-
Pentamethylene-1,3-dioxane-4,6-
Gradually add 3.0g of Zion. 15 minutes at this temperature,
Stir at room temperature for 30 minutes, cool on ice again, and add 4.7 g of 2-methylthio-1,3-dithiolium iodide.
Add. Then stir at room temperature for 15 hours. After the reaction,
Pour the reaction solution into 100ml of ice water, collect the precipitated crystals,
Wash with ether. The crude crystals were recrystallized from dichloromethane-methanol to give crystals with a mp of 245 to 246°C, 5-(1,3-dithiol-2-ylidene)-2,2-pentamethylene-1,3-dioxane-4,6- 3.6g of dione (compound 1)
(78%) obtained. The elemental analysis and 1 H-NMR (proton nuclear magnetic resonance) are shown in Table 1. Examples 2 to 6 Compounds 2 to 6 were synthesized in the same manner as in Example 1. The physical constants of Compounds 2 to 6 are shown in Table 1. In elemental analysis, (C) shows calculated values, and (F) shows analytical values.
【表】【table】
Claims (1)
数１〜５のアルキル基、フエニル基又は互いに結
合して隣接炭素原子と共に炭素数５〜６のシクロ
アルキル基を示す）で表わされる１，３−ジチオ
ール誘導体。[Claims] 1. General formula (In the formula, R 1 and R 2 are the same or different and represent hydrogen, an alkyl group having 1 to 5 carbon atoms, a phenyl group, or a cycloalkyl group having 5 to 6 carbon atoms bonded together with adjacent carbon atoms) 1,3-dithiol derivative.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25888884A JPS61137883A (en) | 1984-12-06 | 1984-12-06 | 1,3-ditiol derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25888884A JPS61137883A (en) | 1984-12-06 | 1984-12-06 | 1,3-ditiol derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61137883A JPS61137883A (en) | 1986-06-25 |
| JPH0380156B2 true JPH0380156B2 (en) | 1991-12-24 |
Family
ID=17326421
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP25888884A Granted JPS61137883A (en) | 1984-12-06 | 1984-12-06 | 1,3-ditiol derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61137883A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH067273A (en) * | 1993-04-01 | 1994-01-18 | Oshitani Sangyo Kk | Manufacture of dust collection pack for cleaner |
-
1984
- 1984-12-06 JP JP25888884A patent/JPS61137883A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS61137883A (en) | 1986-06-25 |
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