JPH0136477B2 - - Google Patents
Info
- Publication number
- JPH0136477B2 JPH0136477B2 JP3286981A JP3286981A JPH0136477B2 JP H0136477 B2 JPH0136477 B2 JP H0136477B2 JP 3286981 A JP3286981 A JP 3286981A JP 3286981 A JP3286981 A JP 3286981A JP H0136477 B2 JPH0136477 B2 JP H0136477B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- oxabicyclo
- present
- general formula
- melting point
- 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
- NVORRKXXHHFWDH-UHFFFAOYSA-N 3-oxabicyclo[2.2.2]octan-2-one Chemical class C1CC2C(=O)OC1CC2 NVORRKXXHHFWDH-UHFFFAOYSA-N 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- -1 4-n-pentyl-2-oxabicyclo[2,2,2]octan-3-one Chemical compound 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- 238000000921 elemental analysis Methods 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000003266 anti-allergic effect Effects 0.000 description 3
- 230000003356 anti-rheumatic effect Effects 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- MNDIARAMWBIKFW-UHFFFAOYSA-N 1-bromohexane Chemical compound CCCCCCBr MNDIARAMWBIKFW-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- ANYSGBYRTLOUPO-UHFFFAOYSA-N lithium tetramethylpiperidide Chemical compound [Li]N1C(C)(C)CCCC1(C)C ANYSGBYRTLOUPO-UHFFFAOYSA-N 0.000 description 1
- UPRXAOPZPSAYHF-UHFFFAOYSA-N lithium;cyclohexyl(propan-2-yl)azanide Chemical compound CC(C)N([Li])C1CCCCC1 UPRXAOPZPSAYHF-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Description
【発明の詳細な説明】
本発明は一般式（）
（式中、ＲはC2〜C10の直鎖アルキル基又は分枝
アルキル基を意味する）で表わされる新規な２−
オキサビシクロ〔２，２，２〕オクタン−３−オ
ン誘導体に関するものである。[Detailed Description of the Invention] The present invention relates to the general formula () A novel 2-
It relates to oxabicyclo[2,2,2]octan-3-one derivatives.
本発明の化合物は文献未載の新規化合物であ
り、抗腫瘍作用、抗アレルギー作用、肝機能改善
作用、抗リウマチ作用等の薬理作用を有し医薬品
として非常に有用な化合物である。 The compound of the present invention is a novel compound that has not been described in any literature, and has pharmacological effects such as antitumor action, antiallergic action, liver function improving action, and antirheumatic action, and is a very useful compound as a pharmaceutical.
又、本発明の化合物は抗腫瘍作用、抗アレルギ
ー作用、肝機能改善作用、抗リウマチ作用等の薬
理作用を有し医薬品として有用な化合物であると
して別に本願出願人が特許を受けるべく出願中の
化合物を合成する上での中間体としても非常に有
用な化合物である。 The compound of the present invention has pharmacological effects such as anti-tumor activity, anti-allergic effect, liver function improving effect, and anti-rheumatic effect, and is a useful compound as a pharmaceutical. It is also a very useful compound as an intermediate in the synthesis of other compounds.
従来、抗腫瘍剤としては一般にアルキル化剤、
代謝拮抗剤等が臨床上用いられているが、概して
副作用が強くその使用が制限されているのが現状
である。そこで本発明者等は副作用の弱い新規な
抗腫瘍活性化合物を求め鋭意研究を重ねた結果、
一般式（）で表わされる新規化合物の合成に成
功し、薬理作用について種々検討したところ、こ
れらの化合物が顕著な抗腫瘍作用、抗アレルギー
作用、肝機能改善作用、抗リウマチ作用等の薬理
作用を有し、且つ副作用が皆無に等しいことを見
出し本発明を完成したのである。 Conventionally, antitumor agents generally include alkylating agents,
Although antimetabolites and the like are used clinically, their use is currently limited due to their generally strong side effects. Therefore, the present inventors conducted extensive research in search of a new antitumor active compound with weak side effects, and as a result,
After successfully synthesizing new compounds represented by the general formula () and conducting various studies on their pharmacological effects, we found that these compounds have remarkable pharmacological effects such as anti-tumor, anti-allergic, liver function-improving, and anti-rheumatic effects. The present invention was completed based on the discovery that the present invention has no side effects.
次に本発明の製造法について説明するが、これ
は一例にすぎず勿論他の化学的類似方法によつて
も製造できるものである。 Next, the manufacturing method of the present invention will be explained, but this is only an example, and it goes without saying that it can also be manufactured by other chemically similar methods.
製造法Ａ
但し、式中ＲはC2〜C10の直鎖アルキル基又は
分枝アルキル基を意味する。Manufacturing method A However, in the formula, R means a C2 to C10 straight chain alkyl group or a branched alkyl group.
製造法Ｂ
但し、式中Ｒは前記と同じ意味を有し、Ｘはハ
ロゲン原子を意味する。Manufacturing method B However, in the formula, R has the same meaning as above, and X means a halogen atom.
尚、前記製造法Ａの出発物質である一般式
（）で表わされる化合物は本願出願人が特許を
受けるべく本願と並行して出願中の特許出願（特
願昭56−32867号）に記載の方法により合成すれ
ばよい。 The compound represented by the general formula ( It can be synthesized by any method.
又、製造法Ｂの出発物質である化合物（）の
合成は例えばホール・ジユニア（H.K.Hall Jr.）
等のジヤーナル・オブ・ザ・アメリカン・ケミカ
ル・ソサエテイー（Journal of the American
Chemical Society）80、6412（’58）に準じて行
なえばよい。 In addition, the compound (), which is the starting material for production method B, can be synthesized by, for example, Hall Giuniar (HKHall Jr.).
Journal of the American Chemical Society, etc.
Chemical Society) 80 , 6412 ('58).
前記製造法について具体的に説明すると、製造
法Ａは一般式（）で表わされる化合物を180〜
220℃にて単に加熱すればよい。 To specifically explain the above manufacturing method, manufacturing method A uses a compound represented by the general formula () from 180 to
Simply heat at 220°C.
製造法Ｂは窒素気流中にて化合物（）を塩基
（例えばｎ−ブチルリチウム、リチウムジイソプ
ロピルアミド、リチウムシクロヘキシルイソプロ
ピルアミド、リチウム２，２，６，６−テトラメ
チルピペリジド、リチウムジシクロヘキシルアミ
ド等）の存在下、不活性溶媒（例えばジエチルエ
ーテル、テトラヒドロフラン等）中、一般式
（）で表わされるアルキルハライドと反応させ
ればよい。 Production method B involves adding the compound () to a base (e.g. n-butyllithium, lithium diisopropylamide, lithium cyclohexylisopropylamide, lithium 2,2,6,6-tetramethylpiperidide, lithium dicyclohexylamide, etc.) in a nitrogen stream. may be reacted with an alkyl halide represented by the general formula () in the presence of an inert solvent (eg diethyl ether, tetrahydrofuran, etc.).
以下に実施例を示し本発明を更に具体的に説明
する。 EXAMPLES The present invention will be explained in more detail with reference to Examples below.
実施例 １
シス−４−ヒドロキシ−１−ｎ−ペンチルシク
ロヘキサンカルボン酸３ｇを180℃で４時間加熱
した。冷後生成した結晶をヘキサンより再結晶す
ると無色針状晶の４−ｎ−ペンチル−２−オキサ
ビシクロ〔２，２，２〕オクタン−３−オン2.3
ｇを得た。Example 1 3 g of cis-4-hydroxy-1-n-pentylcyclohexanecarboxylic acid was heated at 180°C for 4 hours. When the crystals formed after cooling are recrystallized from hexane, colorless needle-like crystals of 4-n-pentyl-2-oxabicyclo[2,2,2]octan-3-one 2.3
I got g.
この物質の融点及び元素分析値は次の通りであ
つた。 The melting point and elemental analysis values of this substance were as follows.
融 点 37〜38℃
元素分析値 C12H20O2
理論値 Ｃ：73.43 Ｈ：10.27
実測値 Ｃ：73.50 Ｈ：10.22
実施例 ２
ジイソプロピルアミン20.2ｇとテトラヒドロフ
ラン300mlの混液を−15℃に冷却し、15％ｎ−ブ
チルリチウムのヘキサン溶液150mlを窒素気流中
徐々に滴下した。滴下後40分間−15℃にて撹拌
し、次いで２−オキサビシクロ〔２，２，２〕オ
クタン−３−オン23.2ｇを加え、更に−10〜０℃
にてｎ−ヘキシルブロミド33ｇを加えて２時間反
応させた。反応終了後、飽和塩化アンモニウム水
溶液を加え溶媒を留去した。残渣にエーテルを加
え水洗、脱水後エーテルを留去し、シリカゲル・
イソプロピルエーテルカラムクロマトグラフイー
に付して精製しヘキサンより再結晶すると無色針
状晶の４−ｎ−ヘキシル−２−オキサビシクロ
〔２，２，２〕オクタン−３−オン4.6ｇを得た。Melting point 37-38°C Elemental analysis value C 12 H 20 O 2 Theoretical value C: 73.43 H: 10.27 Actual value C: 73.50 H: 10.22 Example 2 A mixture of 20.2 g of diisopropylamine and 300 ml of tetrahydrofuran was cooled to -15°C. , 150 ml of a 15% hexane solution of n-butyllithium was gradually added dropwise in a nitrogen stream. After dropping, stir at -15℃ for 40 minutes, then add 23.2g of 2-oxabicyclo[2,2,2]octan-3-one, and then stir at -10 to 0℃.
33 g of n-hexyl bromide was added thereto and reacted for 2 hours. After the reaction was completed, a saturated aqueous ammonium chloride solution was added and the solvent was distilled off. Ether was added to the residue, washed with water, dehydrated, the ether was distilled off, and silica gel
The product was purified by isopropyl ether column chromatography and recrystallized from hexane to obtain 4.6 g of 4-n-hexyl-2-oxabicyclo[2,2,2]octan-3-one as colorless needles.
この物質の融点及び元素分析値は次の通りであ
つた。 The melting point and elemental analysis values of this substance were as follows.
融 点 35〜36℃
元素分析値 C13H22O2
理論値 Ｃ：74.24 Ｈ：10.54
実測値 Ｃ：72.30 Ｈ：10.49
以下前記実施例の方法に準じて次の化合物を合
成した。Melting point: 35-36°C Elemental analysis value: C 13 H 22 O 2 Theoretical value: C: 74.24 H: 10.54 Actual value: C: 72.30 H: 10.49 The following compounds were synthesized according to the method of the above example.
４−ｎ−ブチル−２−オキサビシクロ〔２，
２，２〕オクタン−３−オン
沸 点 116〜119℃／4.5mmHg
４−イソブチル−２−オキサビシクロ〔２，
２，２〕オクタン−３−オン
融 点 71〜72℃ 4-n-butyl-2-oxabicyclo[2,
2,2]Octane-3-one Boiling point 116-119℃/4.5mmHg 4-isobutyl-2-oxabicyclo[2,
2,2]Octane-3-one Melting point 71-72℃
Claims (1)
アルキル基を意味する）で表わされる新規な２−
オキサビシクロ〔２，２，２〕オクタン−３−オ
ン誘導体。[Claims] 1. General formula A novel 2-
Oxabicyclo[2,2,2]octan-3-one derivative.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3286981A JPS57145881A (en) | 1981-03-05 | 1981-03-05 | Novel 2-oxabicyclo(2,2,2)octane-3-one derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3286981A JPS57145881A (en) | 1981-03-05 | 1981-03-05 | Novel 2-oxabicyclo(2,2,2)octane-3-one derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS57145881A JPS57145881A (en) | 1982-09-09 |
| JPH0136477B2 true JPH0136477B2 (en) | 1989-07-31 |
Family
ID=12370861
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3286981A Granted JPS57145881A (en) | 1981-03-05 | 1981-03-05 | Novel 2-oxabicyclo(2,2,2)octane-3-one derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS57145881A (en) |
-
1981
- 1981-03-05 JP JP3286981A patent/JPS57145881A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS57145881A (en) | 1982-09-09 |
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