JPH0687812A - Oxime compounds and their o-acyl derivative having physiological activity - Google Patents
Oxime compounds and their o-acyl derivative having physiological activityInfo
- Publication number
- JPH0687812A JPH0687812A JP4262995A JP26299592A JPH0687812A JP H0687812 A JPH0687812 A JP H0687812A JP 4262995 A JP4262995 A JP 4262995A JP 26299592 A JP26299592 A JP 26299592A JP H0687812 A JPH0687812 A JP H0687812A
- Authority
- JP
- Japan
- Prior art keywords
- solution
- compound
- agent
- group
- oxime 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.)
- Pending
Links
- -1 Oxime compounds Chemical class 0.000 title abstract description 7
- 230000001766 physiological effect Effects 0.000 title 1
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 11
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 125000003118 aryl group Chemical group 0.000 claims abstract description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 4
- 239000004480 active ingredient Substances 0.000 claims description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 9
- 150000001875 compounds Chemical class 0.000 abstract description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 abstract description 5
- 150000002430 hydrocarbons Chemical class 0.000 abstract description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 5
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 abstract description 4
- 239000002260 anti-inflammatory agent Substances 0.000 abstract description 4
- 235000019441 ethanol Nutrition 0.000 abstract description 4
- 239000000921 anthelmintic agent Substances 0.000 abstract description 2
- 229940121375 antifungal agent Drugs 0.000 abstract description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 1
- 239000004215 Carbon black (E152) Substances 0.000 abstract 1
- 230000001741 anti-phlogistic effect Effects 0.000 abstract 1
- 239000003429 antifungal agent Substances 0.000 abstract 1
- 230000001747 exhibiting effect Effects 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 abstract 1
- 239000008240 homogeneous mixture Substances 0.000 abstract 1
- 229930195733 hydrocarbon Natural products 0.000 abstract 1
- 150000002576 ketones Chemical class 0.000 abstract 1
- 150000002923 oximes Chemical class 0.000 description 17
- 206010030113 Oedema Diseases 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- 229920001525 carrageenan Polymers 0.000 description 7
- 230000003110 anti-inflammatory effect Effects 0.000 description 6
- 235000010418 carrageenan Nutrition 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 5
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
- 150000001728 carbonyl compounds Chemical class 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000000921 elemental analysis Methods 0.000 description 4
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 4
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229960003512 nicotinic acid Drugs 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- 229940081066 picolinic acid Drugs 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- ISCMYZGMRHODRP-UHFFFAOYSA-N 3-(iminomethylideneamino)-n,n-dimethylpropan-1-amine Chemical compound CN(C)CCCN=C=N ISCMYZGMRHODRP-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 230000006179 O-acylation Effects 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- IYKFYARMMIESOX-UHFFFAOYSA-N adamantanone Chemical compound C1C(C2)CC3CC1C(=O)C2C3 IYKFYARMMIESOX-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 230000000507 anthelmentic effect Effects 0.000 description 1
- 229940124339 anthelmintic agent Drugs 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- WIRUZQNBHNAMAB-UHFFFAOYSA-N benzene;cyclohexane Chemical compound C1CCCCC1.C1=CC=CC=C1 WIRUZQNBHNAMAB-UHFFFAOYSA-N 0.000 description 1
- CMWYOMQKNDVFMD-UHFFFAOYSA-N benzene;pentane Chemical compound CCCCC.C1=CC=CC=C1 CMWYOMQKNDVFMD-UHFFFAOYSA-N 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- UFEJKYYYVXYMMS-UHFFFAOYSA-N methylcarbamic acid Chemical class CNC(O)=O UFEJKYYYVXYMMS-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、新規なオキシム類を含
むオキシム類、そのＯ−アシル化合物、およびその医薬
分野における消炎剤、農薬分野における防かび、駆虫剤
としての用途に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to oximes including novel oximes, O-acyl compounds thereof, and their use as antiphlogistic agents in the field of medicine, fungicides in the field of agrochemicals, and as anthelmintic agents.
【０００２】[0002]
【従来の技術とその問題点】カルボニル化合物の結晶性
誘導体としてのオキシム類は公知であるがその生理的機
能についてはあまり知られていない。たとえば２−アダ
マンタノンのオキシムについてはそのエステルが消炎作
用を示すこと、また抗ウイスル作用を示すことが知られ
ている（特開昭６０−４８９５９号）が、その化学構造
と生理作用の関係は未だ不明である。さらにオキシム類
のＮ−メチルカルバミン酸エステルの殺虫作用について
はあるものについては殺虫作用があることが公知である
が、一般的なエステルについて知られていることはな
い。本発明者らは新規なオキシム類を含むオキシム類
と、そのアシル誘導体が消炎作用を示し、また一方にお
いて防かび、駆虫作法を示すことを見出し、この知見に
よって本発明を完成するに至った。以上の記述から明ら
かなように本発明の目的は、上述式（Ｉ）で示される新
規な生理活性を有するオキシム類およびそれらのＯ−ア
シル誘導体を提供することである。2. Description of the Related Art Oximes as crystalline derivatives of carbonyl compounds are known, but their physiological functions are not well known. For example, with respect to the oxime of 2-adamantanone, it is known that its ester shows an anti-inflammatory action and an anti-virus effect (JP-A-60-48959), but the relationship between its chemical structure and physiological action is known. It is still unknown. Further, it is known that some N-methylcarbamic acid esters of oximes have an insecticidal action, but nothing is known about general esters. The present inventors have found that oximes including novel oximes and their acyl derivatives exhibit anti-inflammatory action, and, on the other hand, exhibit antifungal and anthelmintic methods, and have completed the present invention based on this finding. As is clear from the above description, an object of the present invention is to provide novel physiologically active oximes represented by the above formula (I) and O-acyl derivatives thereof.
【０００３】[0003]
【問題点を解決するための手段】本発明は、下記（１）
および（２）の構成を有する。 （１）一般式The present invention includes the following (1).
And (2). (1) General formula
【０００４】[0004]
【化３】 [Chemical 3]
【０００５】［式中、Ｒ1 およびＲ2 はアルキル基、ア
ルアルキル基、芳香族炭素環、またはヘテロ環基、Ｒ3
は中級炭化水素基、ヘテロ環基を表わす］を有する化合
物。 （２）一般式[Wherein R 1 and R 2 are an alkyl group, an aralkyl group, an aromatic carbocycle, or a heterocyclic group, R 3
Represents an intermediate hydrocarbon group or a heterocyclic group]. (2) General formula
【０００６】[0006]
【化４】 [Chemical 4]
【０００７】［式中、Ｒ1 およびＲ2 はアルキル基、芳
香族炭素環、またはヘテロ環基、Ｒ3 は中級炭化水素
基、ヘテロ環基を表わす］を有する化合物を有効成分と
する消炎剤。Anti-inflammatory agent containing a compound having [wherein R 1 and R 2 represent an alkyl group, an aromatic carbocycle or a heterocyclic group and R 3 represents a middle hydrocarbon group or a heterocyclic group] as an active ingredient .
【０００８】本発明の構成と効果につき以下に詳述す
る。上記一般式（Ｉ）の記号の定義においてアルキル
基、アルアルキル基におけるアルキルの語は炭素数３以
下の直鎖、または分枝アルキル基をいう。芳香族炭素環
とは置換基を有する芳香族炭化水素残基をいう。ヘテロ
環とは、酸素、窒素、またはその両方を含む芳香性、ま
たは非芳香性の環状化合物残基をいう。中級炭化水素基
とは、天然界に広く分布する炭素中１０個ないし２０
個、好ましくは炭素数１０個ないし１８個の飽和、不飽
和炭化水素基をいう。オキシムの合成法はカルボニル化
合物とヒドロキシアミンとの反応で得られる（日本化学
会編新実験化学講座有機構造〔Ｉ〕６６頁（１９７７）
丸喜株式会社）。Ｏーアシル化はいわゆる（３−ジメチ
ルアミノプロピル）カルボジイミド（以下ＥＤＣＩ）／
４−ジメチルアミノピリジン（以下ＤＭＡＰ）法、また
は混合酸無水物法によって得られる。The structure and effect of the present invention will be described in detail below. In the definition of the symbol of the above general formula (I), the term alkyl in the alkyl group and aralkyl group means a straight chain or branched alkyl group having 3 or less carbon atoms. The aromatic carbocycle refers to an aromatic hydrocarbon residue having a substituent. Heterocycle refers to an aromatic or non-aromatic cyclic compound residue containing oxygen, nitrogen, or both. Intermediate hydrocarbon group means 10 to 20 carbon atoms widely distributed in the natural world.
And preferably saturated or unsaturated hydrocarbon groups having 10 to 18 carbon atoms. The oxime can be prepared by the reaction of a carbonyl compound and hydroxyamine (Organic Structure [I] page 66 (1977), New Experimental Chemistry, edited by The Chemical Society of Japan).
Maruki Co., Ltd.). O-acylation is the so-called (3-dimethylaminopropyl) carbodiimide (hereinafter EDCI) /
It is obtained by the 4-dimethylaminopyridine (hereinafter DMAP) method or the mixed acid anhydride method.
【０００９】その活性を測定したオキシム１〜１５を表
１および表２に示す。化合物１３，１４および１５は新
規化合物である。The oximes 1 to 15 whose activity was measured are shown in Tables 1 and 2. Compounds 13, 14 and 15 are new compounds.
【００１０】[0010]
【表１】 [Table 1]
【００１１】[0011]
【表２】 [Table 2]
【００１２】これらに対してラウリン酸、ピコリン酸、
ニコチン酸、およびイソニコチン酸を反応させて１Ｌか
ら１５Ｌまで４１種類の新規化合物とそれぞれの物性、
元素分析値を表３に示した。以下実施例、使用例によっ
て本発明を説明する。For these, lauric acid, picolinic acid,
By reacting nicotinic acid and isonicotinic acid, 41 kinds of novel compounds from 1 L to 15 L and their respective physical properties,
The elemental analysis values are shown in Table 3. The present invention will be described below with reference to examples and usage examples.
【００１３】実施例１．メチルパラモルフォリノフェニ
ルケトオキシム ヒドロキシルアミン塩酸塩２．０５部を水１０部に溶解
し、これに１−Ｎ−水酸化ナトリウム２０部を加え、さ
らにメチルパラモルフォリノフェニルケトン１部を加え
る。エチルアルコール約２０部を加えてほぼ均一な混液
とし、水浴上で約５０℃に約２０分間加温し、氷冷下に
一夜放置する。析出した結晶を濾取し、クロロホルムか
ら再結晶する。収率６８．８％．融点１８２〜１８５
℃．Ｍｓm/z : ２１８（Mt).元素分析値（C12H16N2O2):
理論値Ｃ，６５．４３；Ｈ，７．３２；Ｎ，１２．７
２．実測値Ｃ，６５．２８；Ｈ，７．４３；Ｎ，１２．
６４．Embodiment 1. Methylparamorpholinophenyl ketoxime 2.05 parts of hydroxylamine hydrochloride are dissolved in 10 parts of water, 20 parts of 1-N-sodium hydroxide are added thereto, and further 1 part of methylparamorpholinophenyl ketone is added. Approximately 20 parts of ethyl alcohol is added to form a substantially uniform mixed solution, which is heated to about 50 ° C. for about 20 minutes on a water bath and left overnight under ice cooling. The precipitated crystals are collected by filtration and recrystallized from chloroform. Yield 68.8%. Melting point 182-185
° C. Ms m / z: 218 (M t ). Elemental analysis value (C 12 H 16 N 2 O 2 ):
Theoretical C, 65.43; H, 7.32; N, 12.7
2. Found C, 65.28; H, 7.43; N, 12.
64.
【００１４】実施例２．メチルパラモルホリノフェニル
ケトオキシム 実施例１においてカルボニル化合物としてメチルパラモ
ルホリノフェニルケトンを用いる以外は同様に処理して
粗結晶を得、さらにベンゼン−ｎ−ペンタン混液から再
結晶して相当するオキシムを９１．９％の収率で得た。
融点１６２〜１６４℃．Ｍｓm/z : ２１８（Mt).元素分
析値（C13H18N2O): 理論値Ｃ，７１．５３；Ｈ，８．３
１；Ｎ，１２．８３．実測値Ｃ，７１．７５；Ｈ，８．
５２；Ｎ，１２．７７．Example 2. Methylparamorpholinophenyl ketoxime In the same manner as in Example 1 except that methylparamorpholinophenylketone was used as the carbonyl compound, crude crystals were obtained by the same treatment, and recrystallized from a benzene-n-pentane mixed solution to give the corresponding oxime. Obtained in a yield of 9%.
Melting point 162-164 [deg.] C. Ms m / z: 218 (M t ). Elemental analysis value (C 13 H 18 N 2 O): Theoretical value C, 71.53; H, 8.3
1; N, 12.83. Found C, 71.75; H8.
52; N, 12.77.
【００１５】実施例３．メチルパライミダゾリノフェニ
ルケトオキシム 実施例１においてカルボニル化合物としてメチルパライ
ミダゾリノフェニルケトンを用いる以外は同様に処理し
て粗結晶を得、エタノールで再結晶して相当するオキシ
ムを９４．８％の収率で得た。融点２０２〜２０５℃．
Ｍｓm/z : ２０１（Mt).元素分析値（C11H11N3O): 理論
値Ｃ，６５．６６；Ｈ，５．５１；Ｎ，２０．８８．実
測値Ｃ，６５．５０；Ｈ，５．５３；Ｎ，２０．６３．Example 3. Methylparaimidazolinophenylketoxime In the same manner as in Example 1 except that methylparaimidazolinophenylketone was used as the carbonyl compound, crude crystals were obtained in the same manner and recrystallized from ethanol to obtain the corresponding oxime with a yield of 94.8%. Got at a rate. Melting point 202-205 ° C.
Ms m / z: 201 (M t ). Elemental analysis value (C 11 H 11 N 3 O): Theoretical value C, 65.66; H, 5.51; N, 20.88. Found C, 65.50; H, 5.53; N, 20.63.
【００１６】実施例４．Ｏ−アシルオキシム合成一般操
作法（EDCI/DMAP 法） オキシム１当量、ＤＭＡＰ ０．１当量、カルボン酸１
当量、およびＥＤＣＩ塩酸塩１．１当量を氷冷下攪拌し
ながら適当量の塩化メチレン（CH2Cl2) に加え、そのま
ま１時間攪拌を続ける。 注）適当量：およそ原料の総和の２０位（重量）。 反応終了後室温に一夜放置した後、酸性炭酸ナトリウ
ム、さらに水で洗浄し、無水硫酸マグネシウムで乾燥後
減圧下に溶媒を留去する。残分をシリカゲルクロマトグ
ラフィーで精精し、要すればさらに再結晶して精製す
る。結果を表３に示した。Example 4. General procedure for O-acyl oxime synthesis (EDCI / DMAP method) 1 equivalent of oxime, 0.1 equivalent of DMAP, 1 carboxylic acid
Equivalent amount and 1.1 equivalent amount of EDCI hydrochloride are added to an appropriate amount of methylene chloride (CH 2 Cl 2 ) while stirring under ice cooling, and the stirring is continued for 1 hour. Note) Appropriate amount: Approximately 20th (weight) of the total of raw materials. After completion of the reaction, the mixture is left overnight at room temperature, washed with sodium acid carbonate and further with water, dried over anhydrous magnesium sulfate, and the solvent is distilled off under reduced pressure. The residue is purified by silica gel chromatography and, if necessary, recrystallized for purification. The results are shown in Table 3.
【００１７】実施例５．Ｏ−アシルオキシム合成一般操
作法（混合酸無水物法） カルボン酸のカリウム塩１当量を適当量の塩化メチレン
にけん濁させ、−１５℃において攪拌下にクロロギ酸エ
チル１当量、および１滴を加える。３０分後オキシム１
当量の無水塩化メチレン溶液を徐々に加え、さらに攪拌
下２時間室温で反応させる。沈殿を濾別し、濾液を水洗
した後、無水硫酸マグネシウムで乾燥し、溶媒を留去、
生成物をベンゼン−シクロヘキサン溶液から再結晶す
る。結果を表３に示した。Embodiment 5. General procedure for O-acyloxime synthesis (mixed acid anhydride method) 1 equivalent of potassium salt of carboxylic acid was suspended in an appropriate amount of methylene chloride, and 1 equivalent of ethyl chloroformate and 1 drop were added with stirring at -15 ° C. Add. 30 minutes later oxime 1
An equivalent amount of anhydrous methylene chloride solution is gradually added, and the mixture is further reacted for 2 hours at room temperature with stirring. The precipitate was filtered off, the filtrate was washed with water, dried over anhydrous magnesium sulfate, the solvent was distilled off,
The product is recrystallized from a benzene-cyclohexane solution. The results are shown in Table 3.
【００１８】[0018]
【表３】 [Table 3]
【００１９】使用例 抗炎症作用は常法下記のカラゲーニン足浮腫法によって
測定した。すなわち、体重１６０ｇないし１８０ｇのス
プラーグ−ドーレイ種（Sprague-Dawley種の雄ラット６
匹を１群とし、それぞれの左の足（注：正確にはあしの
うら）にλ−カラゲーナンの０．１％生理食塩水を注射
して浮腫をつくらせる。３０分後、オキシム、およびそ
のエステルを経口投与し、１時間ごとに７時間まで浮腫
の減少量を測定する。コントロールには０．３％エチル
アルコール＋０．３％レシチン水溶液を用いた。 （薬物による）浮腫抑制効果（％）＝（Ｅｃ−Ｅｔ）／
Ｅｃ×１００ Ｅｃ：コントロール動物の平均浮腫量 Ｅｔ：薬物投与動物の平均浮腫量 表４および図１に浮腫抑制効果（％）を示す。Example of Use The anti-inflammatory effect was measured by the following method, the carrageenin paw edema method. That is, 6 Sprague-Dawley male rats weighing 160 to 180 g
One group of animals is taken and each left foot (note: to be exact, Ashinoura) is injected with 0.1% saline of λ-carrageenan to cause edema. After 30 minutes, oxime and its ester are orally administered, and the reduction amount of edema is measured every hour for up to 7 hours. A 0.3% ethyl alcohol + 0.3% lecithin aqueous solution was used as a control. Edema inhibitory effect (by drug) (%) = (Ec-Et) /
Ec × 100 Ec: Average edema amount of control animals Et: Average edema amount of drug-administered animals Table 4 and FIG. 1 show the edema inhibitory effect (%).
【００２０】カラゲニンの足浮腫ラットにおけるオキシ
ム、Ｏ−アシルオキシム、および関連化合物の抗炎症作
用（浮腫形成のあと３時間経過時点で化合物３０ｍｇ／
ｋｇを経口投与；抑制率で表示）Carrageenin paw edema Anti-inflammatory effects of oximes, O-acyl oximes, and related compounds in rats (30 mg / compound 3 hours after edema formation)
Oral administration of kg; expressed as suppression rate)
【表４】 註．ａ）％表示の数値において、浮腫抑制率が±１０％
以下の場合は無効（ｎ）とした。 ｂ）Ｐ：ピコリン酸、Ｎ：ニコチン酸、Ｉ：イソニコチ
ン酸 ※ 対象群に対し顕著に差異があった、Ｐ：＜０．０５ ※ 同じ Ｐ：＜０．０１ 参考：抗炎症剤インドメタシンでは、４６Ｗ（１０ｍｇ
／ｋｇ経口投与）の抑止率であった。[Table 4] Note. a) The edema suppression rate is ± 10% in the numerical value of% display.
The following cases were considered invalid (n). b) P: picolinic acid, N: nicotinic acid, I: isonicotinic acid * There was a significant difference from the control group, P: <0.05 * Same P: <0.01 Reference: In anti-inflammatory drug indomethacin , 46W (10mg
/ Kg oral administration).
【００２１】[0021]
【図１】 註，１．カラゲニンによる足浮腫ラットにおけるアスピ
リンと化合物１Ｌ，１Ｎの効果：カラゲニン誘導浮腫は
ラットの左足裏に１ｍｇのλ（ラムダ）カラゲニン注射
で得た。薬物量（３０ｍｇ／ｋｇ）はカラゲニン注射
０．５時間前に経口投与した。それぞれの測定点は、±
Ｓ，Ｅの平均値を示す。 ※Ｐ＜０．０５および※※Ｐ＜０．０１で、対照と比較
してある。 註，２．Ｃ．Ａ．Ｗｉｎｔｅｒ，Ｅ．Ａ．Ｒｉｓｌｅ
ｙ，Ｇ．Ｗ．Ｎｕｓｓ，Ｐｒｏｃ．Ｓｏｃ．Ｅｘｐ．Ｍ
ｅｄ．，１１１，５４４（１９６２）．[Figure 1] Notes, 1. Carrageenin-induced paw edema Effect of aspirin and compounds 1L, 1N in rats: Carrageenin-induced edema was obtained by injection of 1 mg lambda (lambda) carrageenin in the left sole of the rat. The drug amount (30 mg / kg) was orally administered 0.5 hours before the injection of carrageenin. Each measurement point is ±
The average value of S and E is shown. * P <0.05 and ** P <0.01, compared to the control. Note, 2. C. A. Winter, E.I. A. Risle
y, G. W. Nuss, Proc. Soc. Exp. M
ed. , 111, 544 (1962).
【００２２】[0022]
【発明の効果】以上に詳述したように、本発明のαオキ
シムおよびそのエステルは、顕著な消炎作用を示す。INDUSTRIAL APPLICABILITY As described above in detail, the α-oxime and its ester of the present invention exhibit a remarkable anti-inflammatory effect.
図１は、本発明のオキシムまたはそのエステルの消炎作
用を示す使用例の説明である。FIG. 1 is an illustration of a use example showing the anti-inflammatory action of the oxime or its ester of the present invention.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.5 識別記号 庁内整理番号 ＦＩ 技術表示箇所 Ｃ０７Ｄ 211/26 9165−4Ｃ 233/61 １０２ 295/12 // Ａ０１Ｎ 37/06 8930−4Ｈ ─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. 5 Identification code Office reference number FI technical display location C07D 211/26 9165-4C 233/61 102 295/12 // A01N 37/06 8930-4H
Claims (2)
基、芳香族炭素環、またはヘテロ環基、Ｒ3 は中級炭化
水素基、ヘテロ環基を表わす］を有する化合物。1. A general formula: [Wherein R 1 and R 2 represent an alkyl group, an aralkyl group, an aromatic carbocycle, or a heterocyclic group, and R 3 represents an intermediate hydrocarbon group or a heterocyclic group].
またはヘテロ環基、Ｒ3 は中級炭化水素基、ヘテロ環基
を表わす］を有する化合物を有効成分とする消炎剤。2. A general formula: [Wherein R 1 and R 2 are an alkyl group, an aromatic carbocycle,
Or a heterocyclic group and R 3 represents a middle hydrocarbon group or a heterocyclic group] as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4262995A JPH0687812A (en) | 1992-09-04 | 1992-09-04 | Oxime compounds and their o-acyl derivative having physiological activity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4262995A JPH0687812A (en) | 1992-09-04 | 1992-09-04 | Oxime compounds and their o-acyl derivative having physiological activity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0687812A true JPH0687812A (en) | 1994-03-29 |
Family
ID=17383441
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4262995A Pending JPH0687812A (en) | 1992-09-04 | 1992-09-04 | Oxime compounds and their o-acyl derivative having physiological activity |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0687812A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0727141A2 (en) * | 1995-01-20 | 1996-08-21 | American Cyanamid Company | Fungicidal methods, compounds and compositions containing benzophenones |
| JP2000109457A (en) * | 1998-08-17 | 2000-04-18 | Givaudan Roure Internatl Sa | Oxime carboxylic acid derivative |
| JP2007197390A (en) * | 2006-01-27 | 2007-08-09 | Fujifilm Corp | Oxime derivative, photosensitive composition, pattern-forming material, photosensitive laminate, pattern-forming device and method for forming pattern |
-
1992
- 1992-09-04 JP JP4262995A patent/JPH0687812A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0727141A2 (en) * | 1995-01-20 | 1996-08-21 | American Cyanamid Company | Fungicidal methods, compounds and compositions containing benzophenones |
| EP0727141A3 (en) * | 1995-01-20 | 1998-01-28 | American Cyanamid Company | Fungicidal methods, compounds and compositions containing benzophenones |
| JP2000109457A (en) * | 1998-08-17 | 2000-04-18 | Givaudan Roure Internatl Sa | Oxime carboxylic acid derivative |
| JP2007197390A (en) * | 2006-01-27 | 2007-08-09 | Fujifilm Corp | Oxime derivative, photosensitive composition, pattern-forming material, photosensitive laminate, pattern-forming device and method for forming pattern |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69737980T2 (en) | NITROSED AND NITROSYLATED ALPHA ADRENEORE RECEPTOR ANTAGONISTS, PREPARATIONS AND THEIR USES | |
| KR930009790B1 (en) | Novel benzothiazole and antirheumatic agent comprising it | |
| EP0288973B1 (en) | Benzothiazolinone derivatives, their production and pharmaceutical composition | |
| JPH04235165A (en) | Intermediate for producing 2-hydroxyindole-1- carboxamide compound effective as analgesic anti-inflammatory | |
| US6043232A (en) | Nitroso esters of beta-oxo-amides and aryl propionic acid derivatives of non-steroidal antiinflammatory drugs | |
| DE60031705T2 (en) | Salicylamide DERIVATIVES | |
| JPS62501703A (en) | Amino-salicylic acid derivatives, their salts, their preparation and pharmaceutical compositions containing them | |
| EP0278453A2 (en) | 2,4- and 2,5-Pyridine-dicarboxylic-acid derivatives, process for their preparation, their use and medicines based on these compounds | |
| DE3306006C2 (en) | ||
| US5258397A (en) | 3-Isoxazoyl derivatives endowed with anticonvulsant activity, procedure for their preparation and their pharmaceutical compositions | |
| US6051588A (en) | Nitroso esters of β-oxo-amides and aryl propionic acid derivatives of non-steroidal antiinflammatory drugs | |
| JPS6251272B2 (en) | ||
| US5464860A (en) | N(pyrazol-3-yl) benzamides and pharmaceutical compositions | |
| KR860000104B1 (en) | Process for preparing 2-pyridine carboxamide derivatives | |
| US3726880A (en) | Organic amides and methods for their production | |
| FR2567887A1 (en) | NEW SUBSTITUTED AMIDES, THEIR PREPARATION AND THE MEDICINES THAT CONTAIN THEM | |
| JPH0687812A (en) | Oxime compounds and their o-acyl derivative having physiological activity | |
| EP0211157B1 (en) | Isoxazole derivatives, process for their preparation and phamaceutical compositions containing them | |
| JPS60184077A (en) | Antiinflammatory oxime precursor drug | |
| US4568690A (en) | 1-Methyl-5-p-methylbenzoylpyrrole-2-acetamidoacetanilides with antiinflammatory, analgesic, antipyretic and anti-platelet aggregant activity | |
| KR880001715B1 (en) | Process for preparing 1-furyl-3,4-dihydro-isoquinolines | |
| US4353923A (en) | Pharmaceutical composition containing a benzofurancarboxamide derivative as the active ingredient | |
| JP2579116B2 (en) | Novel 4-methyl-1,3-oxazole compounds, their preparation and pharmaceutical compositions containing them | |
| US4755523A (en) | Abietamide derivatives | |
| EP0007643B1 (en) | Oxadiazolotriazine derivatives |