JPS5953264B2 - Method for producing novel α-aminooxycarboxylic acid hydrazide derivative - Google Patents

Method for producing novel α-aminooxycarboxylic acid hydrazide derivative

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Publication number
JPS5953264B2
JPS5953264B2 JP57052368A JP5236882A JPS5953264B2 JP S5953264 B2 JPS5953264 B2 JP S5953264B2 JP 57052368 A JP57052368 A JP 57052368A JP 5236882 A JP5236882 A JP 5236882A JP S5953264 B2 JPS5953264 B2 JP S5953264B2
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JP
Japan
Prior art keywords
formula
group
acid
melting point
elemental analysis
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
Application number
JP57052368A
Other languages
Japanese (ja)
Other versions
JPS57192365A (en
Inventor
ラヨス・キスフアルデイ
ラヨス・ダンシ
アグネス・パテイ・ネ−・ルカツ
ジヨルジイ・フエケテ
イストバン・スザボ
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
RIHITAA GEDEON BEGIESUZECHI GIARU AARU TEII
Original Assignee
RIHITAA GEDEON BEGIESUZECHI GIARU AARU TEII
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Application filed by RIHITAA GEDEON BEGIESUZECHI GIARU AARU TEII filed Critical RIHITAA GEDEON BEGIESUZECHI GIARU AARU TEII
Publication of JPS57192365A publication Critical patent/JPS57192365A/en
Publication of JPS5953264B2 publication Critical patent/JPS5953264B2/en
Expired legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C243/00—Compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A61P31/06—Antibacterial agents for tuberculosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/70—Nitro radicals
    • C07D307/71—Nitro radicals attached in position 5
    • C07D307/72—Nitro radicals attached in position 5 with hydrocarbon radicals, substituted by nitrogen-containing radicals, attached in position 2
    • C07D307/73—Nitro radicals attached in position 5 with hydrocarbon radicals, substituted by nitrogen-containing radicals, attached in position 2 by amino or imino, or substituted amino or imino radicals

Description

【発明の詳細な説明】 本発明は新規置換α−アミノオキシ カルボン酸ヒドラ
ジド誘導体の製造方法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing novel substituted α-aminooxycarboxylic acid hydrazide derivatives.

本発明により製造される新規化合物は次式（Ｉ）の化合
物及びその酸付加塩である。The novel compounds produced by the present invention are compounds of the following formula (I) and acid addition salts thereof.

Ｘ二Ｎ−Ｏ−ＣＨ−Ｃｏ−ＮＨ−ＮＨＺ（Ｉ）（式中、
Ｘはシクロペンチリデン基あるいは炭素数１〜５個のア
ルキル、フェニル、ハロフエニル、ヒドロキシフェニル
、ニトロフェニル、アミノフェニル、フリル及びニトロ
フリル基から選んだ少なくとも１個の置換基を有するメ
チレン基を表わし；Ｒは水素、ベンジル基又は随意にメ
チルチオ置換基を有する炭素数１〜５個のアルキル基を
表わし；Ｚはピリジンカルボン酸から誘導されたアシル
基を表わす。X2N-O-CH-Co-NH-NHZ(I) (in the formula,
X represents a cyclopentylidene group or a methylene group having at least one substituent selected from alkyl having 1 to 5 carbon atoms, phenyl, halophenyl, hydroxyphenyl, nitrophenyl, aminophenyl, furyl and nitrofuryl; R represents hydrogen, a benzyl group or an alkyl group having 1 to 5 carbon atoms optionally having a methylthio substituent; Z represents an acyl group derived from pyridinecarboxylic acid.

）本発明により製造される新規化合物は塩基性であり、
酸付加塩を形成し、従つて式（）の化合物の酸付加塩の
製造法も本発明の範囲内に包含される。) The new compound produced by the present invention is basic;
Acid addition salts are formed and therefore processes for preparing acid addition salts of compounds of formula () are also encompassed within the scope of this invention.

式（１）の新規化合物は価値ある薬学的性質を有し、主
として抗結核剤として使用できる。The new compounds of formula (1) have valuable pharmaceutical properties and can be used primarily as antituberculous agents.

英国特許第１３２３１７０号明細書には、遊離又はアシ
ル置換アミノ基を有するある種の抗結核活性のα−アミ
ノオキシ カルボン酸ヒドラジドが記載されている。GB 1323170 describes certain anti-tuberculous active α-aminooxycarboxylic acid hydrazides having free or acyl substituted amino groups.

α−アミノオキシ カルボン酸とカルボニル化合物との
反応は以前から分析の目的で利用されてきた（Ｊ．Ｂｌ
Ｏｌ．Ｃｈｅｍ．リ』，５３９（１９３６）参照）。The reaction between α-aminooxycarboxylic acids and carbonyl compounds has long been used for analytical purposes (J.Bl.
Ol. Chem. 539 (1936)).

かかる反応で生成されるある種のシツフ塩基は植物生長
調整活性を有し（Ｊ．Ａｍ．Ｃｈｅｍ−ＳＯｃ・立』，
７１８（１９４７）参照）、またあるものはビタミンＫ
と同様の作用する（英国特許第６２１９３４号明細書参
照）。Ｊ．Ｍｅｄ．Ｃｈｅｍ．ｌ，８２４（１９６４）
にはα−アミノオキシ酢酸及びα−アミノオキシ酢酸エ
チルのある種のアルドキシム及びケトキシムについて記
載されている。Certain Schiff bases produced in such reactions have plant growth regulating activity (J. Am. Chem-SOc.
718 (1947)), and some contain vitamin K.
(see British Patent No. 621,934). J. Med. Chem. l, 824 (1964)
describes certain aldoximes and ketoximes of α-aminooxyacetic acid and ethyl α-aminooxyacetate.

ある種のα−アミノオキシ カルボン酸から形成される
シツフ塩基は半合成ペニシリン誘導体の研究と関連して
ＡｃｔａＣｈｅｍｉｃａＳｃａｎｄｉｎａｖｉｃａ９ｌ
９ツ３１７（１９６５）に言ウ裁されている。しかしな
がら、これらの文献にはこれらのオキシム及びシツフ塩
基の生物学的作用については何ら言及されていない。Ｈ
ｅｌｖｅｔｉｃａＣｈｉｍｉｃａＡｃｔａ′４６ｐ７６
６（１９６３）には、ある種のアミノオキシカルボン酸
誘導体、特にシツフ塩基の誘導体の制菌活性を調べた結
果、種々の微生物に及ぼされる制菌活性は遊離のアミノ
オキシ基の存在に基因するものであると記述されている
。Schiff bases formed from certain α-aminooxycarboxylic acids have been studied at ActaChemica Scandinavica9l in connection with the study of semisynthetic penicillin derivatives.
It was judged in 9th 317 (1965). However, these documents do not mention anything about the biological effects of these oximes and Schiff bases. H
elveticaChimicaActa'46p76
6 (1963), as a result of investigating the bacteriostatic activity of certain aminooxycarboxylic acid derivatives, particularly derivatives of Schiff bases, it was found that the bacteriostatic activity exerted on various microorganisms is due to the presence of free aminooxy groups. It is described as something.

ＰｒＯｇｒｅｓｓｉｎＭｅｄｉｃｉｎａｌＣｈｅｍｉｓ
ｔｒｙ２ｉ斗１３４８（１９６７）には種々のニトロフ
ルフリリデン鱒導体の制？作用について述べられている
が、それらの抗結核作用については何ら言及されていな
い。PrOgressinMedicinalChemis
Try2i Dou 1348 (1967) includes various nitrofurfurylidene conductor systems. effects are mentioned, but no mention is made of their antituberculous effects.

式（Ｉ）においてＸがモノ置換メチレン基である場合、
その置換基はメチル、エチル、ｎ−プロピル、イソプロ
ピル、ｎ−ブチル、イソブチル又はペンチル基の如きア
ルキル基、随意にハロゲン、ヒドロキシ、ニトロ又はア
ミノ置換基を有するフエニル基あるいはフルフリル又は
ニトロフルフリル基であり得る。When X is a monosubstituted methylene group in formula (I),
The substituents are alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or pentyl groups, phenyl groups or furfuryl or nitrofurfuryl groups optionally with halogen, hydroxy, nitro or amino substituents. could be.

Ｘがジ置換メチレン基の場合にはこれらの置換基を２個
有する。Ｒは水素又はベンジル基あるいは随意にメチル
チオ置換基を有するエチル、プロピル、ブチル又はペン
チル基の如き炭素数１〜５個のアルキル基である。When X is a di-substituted methylene group, it has two of these substituents. R is hydrogen or an alkyl group of 1 to 5 carbon atoms such as benzyl group or ethyl, propyl, butyl or pentyl group optionally with a methylthio substituent.

Ｒが水素以外の基である式（１）の化合物は不整炭素原
子を含むので出発原料に応じて純枠な光学活性異性体又
はラセミ体の形で製造できる。ラセミ化合物はそれ自体
既知の方法で、例えば一対のジアステレオマ一塩の形成
により分割できる。前述の如く、ｚはピリジンカルボン
酸から誘導されるアシル基、例えばイソニコチノイル基
である。Since the compound of formula (1) in which R is a group other than hydrogen contains an asymmetric carbon atom, it can be produced in the form of a pure optically active isomer or a racemate depending on the starting material. Racemates can be resolved in a manner known per se, for example by forming a pair of diastereomeric monosalts. As mentioned above, z is an acyl group derived from pyridinecarboxylic acid, such as an isonicotinoyl group.

本発明によれば、式（１）の化合物は、式（Ｉ［）：（
式中、Ｘ及びＲは前記の意義を有し、ｗは水素、炭素数
１〜５個のアルキル基あるいは１個又は２個以上のハロ
ゲン又はニトロ置換基を有するフエニル基である）のシ
ツフ塩基を式（）：Ｈ２Ｎ−ＮＨＺ（１１１）（式中、
ｚはピリジンカルボン酸から誘導されるアシル基である
）のヒドラジン誘導体と反応させ、ついで所望ならば、
得られた塩基を常法によりその酸付加塩に転化するかあ
るいは得られた塩を常法によりその遊離塩基又は別の塩
に転化することによつて製造される。According to the invention, the compound of formula (1) is a compound of formula (I[):(
In the formula, X and R have the above-mentioned meanings, and w is hydrogen, an alkyl group having 1 to 5 carbon atoms, or a phenyl group having one or more halogen or nitro substituents). The formula (): H2N-NHZ (111) (in the formula,
z is an acyl group derived from pyridine carboxylic acid) and then, if desired,
They are prepared by converting the resulting base into its acid addition salt using conventional methods, or by converting the resulting salt into its free base or another salt using conventional methods.

式（）の化合物において、置換基Ｒ′は水素、メチル、
エチル、プロピル、ブチル又はペンチルあるいは置換フ
エニル、例えばｐ−ニトロフエニル、トリクロロフエニ
ル、トリフルオロフエニル、ペンタクロロフエニル又は
ペンタフルオロフエニル基を表わす。In the compound of formula (), the substituent R' is hydrogen, methyl,
It represents ethyl, propyl, butyl or pentyl or substituted phenyl, such as p-nitrophenyl, trichlorophenyl, trifluorophenyl, pentachlorophenyl or pentafluorophenyl groups.

本発明により製造される化合物はすべて新規であるが、
出発物質は一部は公知であり、新規の出発物質は例えば
パンカリ一特許第１６０１８１号明細書に記載されるよ
うにあるいは後記の実施例で示されるように既知の方法
によつて製造できる。Although all the compounds produced by the present invention are new,
Some of the starting materials are known, and new starting materials can be prepared by known methods, for example as described in Pankali Patent No. 160,181 or as shown in the examples below.

本発明方法の好ましい実施態様においては、式（）の活
性化エステル、好ましくはペンタクロロフエニルエステ
ル、即ちＲ′がエステル形成基、好ましくはペンタクロ
ロフエニル基である化合物又は式（Ｕｆ）のＲ′が水素
である酸のＮ，Ｎ′−ジシクロヘキシルカルボジイミド
を置換ヒドラジド、好ましくはイソニコチン酸ヒドラジ
ドと室温で有機溶剤、好ましくはジメチルホルムアミド
の存在下で反応させる。In a preferred embodiment of the process of the invention, activated esters of the formula (), preferably pentachlorophenyl esters, i.e. compounds in which R' is an ester-forming group, preferably a pentachlorophenyl group, or R' of the formula (Uf) are used. N,N'-dicyclohexylcarbodiimide, an acid in which is hydrogen, is reacted with a substituted hydrazide, preferably isonicotinic acid hydrazide, at room temperature in the presence of an organic solvent, preferably dimethylformamide.

反応混合物は１〜７２時間、好ましくは１６時間放置せ
しめ、ついで副生成物（例えばペンタクロロフエノール
又はＮ，Ｎ／−ジシタロヘキシル尿素）をろ過又は抽出
により除去し、混合物を蒸発させ、所要ならば生成物を
抽出又は晶出により精製する。本発明により製造される
化合物は優れた抗結核活性を有し、特にヒドラジン基上
にイソニコチノイル置換基を有する化合物が有効である
。The reaction mixture is allowed to stand for 1 to 72 hours, preferably 16 hours, then by-products (e.g. pentachlorophenol or N,N/-disitalohexyl urea) are removed by filtration or extraction and the mixture is evaporated to remove the product if necessary. The product is purified by extraction or crystallization. The compounds produced according to the present invention have excellent antituberculous activity, and compounds having an isonicotinoyl substituent on the hydrazine group are particularly effective.

５−ニトロフルフリリデン基を有する化合物はその顕著
なる抗結核活性の他に、ミコバクテリウム属の微生物の
耐性菌に対して有効であるという利点を有する。In addition to their remarkable antituberculous activity, compounds having a 5-nitrofurfurylidene group have the advantage of being effective against resistant microorganisms of the genus Mycobacterium.

本発明者の知る限りでは本発明により製造される化合物
は抗結核活性を有する最初の５−ニトロフルフリリデ７
誘導体である。本発明による新規化合物の試験管内試験
をアルブミン２．５（Ｆｂを含む栄養培地上で行つた。To the best of the inventor's knowledge, the compounds prepared according to the present invention are the first 5-nitrofurfurylide 7 compounds with antituberculous activity.
It is a derivative. In vitro tests of the new compounds according to the invention were carried out on a nutrient medium containing albumin 2.5 (Fb).

供試化合物を含む培地に新鮮なバクテリア培養液０．０
１巧を接種し、３７℃で３週間培養させた。ついで阻止
濃度を測定した。試験に用いたバクテリア菌はミコバク
テリウム ツベルクロシスＨ３，Ｒｖ（Ｍ．ｔ．Ｈ３，
Ｒｖ）、イソニコチノイル ヒドラジド（ＩＮＨ）に耐
性のミコバクテリウム ツベルクロシス（Ｍ．ｔ．）、
ストレプトマイシン（Ｓｔｒｐ．）に耐性のミコバクテ
リウム ツベルクロシス（Ｍ．ｔ．）及びミコバクテリ
ウム カンサシイ（Ｋａｎｓａｓｉｉ）（Ｍ．ｔ．）で
ある。得られた試験結果を第１表に示す。Add 0.0 of a fresh bacterial culture to the medium containing the test compound.
1 Takumi was inoculated and cultured at 37°C for 3 weeks. The inhibitory concentration was then measured. The bacteria used in the test were Mycobacterium tuberculosis H3, Rv (M.t.H3,
Rv), Mycobacterium tuberculosis (M.t.) resistant to isonicotinoyl hydrazide (INH),
Mycobacterium tuberculosis (M.t.) and Mycobacterium Kansasii (M.t.) resistant to streptomycin (Strp.). The test results obtained are shown in Table 1.

本発明により製造される化合牧は経口及び／又は非経口
投与用薬剤の形、例えば錠剤、被覆錠剤、注入性製剤、
坐薬等の形で治療に使用できる。The compounds produced according to the invention can be prepared in the form of pharmaceuticals for oral and/or parenteral administration, such as tablets, coated tablets, injectable preparations,
It can be used for treatment in the form of suppositories.

活性化合物の１日の投与量は哺乳動物の治療には約２〜
８０１！Ｉｆ／Ｋｆｌ好ましくは１０〜５０１１１／Ｑ
であることができ、この量は分割方式で又は遅効性方式
で添加できる。生成物の純度は薄層クロマトグラフイ一
により測定した。The daily dosage of active compound for the treatment of mammals is about 2 to
801! If/Kfl preferably 10-50111/Q
The amount can be added in portions or in a slow-release manner. Product purity was determined by thin layer chromatography.

実施例で示されるＲｆ値は溶離剤としてｎ−ヘキサン、
氷酢酸及びクロロホルムの１：１：８混合物を用いてシ
リカゲル０Ｇ″（Ｓｔａｈｌ）上で測定したものである
。化合物の融点はＤｒ．ＴＯｔｔＯｌｉ型装置を用いて
測定した。得られた化合物の構造は場合により１．Ｒ．
，Ｎ．Ｍ．Ｒ．及び質量スペクトル分析によつて確認し
た。光学活性体の比施光度はオブトン（０ｐｔ０ｎ）施
光計を用いて測定した。次に本発明を実施例により更に
説明する。The Rf values shown in the examples are based on n-hexane as the eluent,
Measured on silica gel 0G'' (Stahl) using a 1:1:8 mixture of glacial acetic acid and chloroform. The melting point of the compound was determined using a Dr. TOttOli type apparatus. In some cases 1.R.
,N. M. R. and confirmed by mass spectrometry. The specific optical density of the optically active substance was measured using an Obton (0pt0n) spectrophotometer. Next, the present invention will be further explained by examples.

実施例 １ Ｎ−（Ｎ″−５−ニトロフルフリリデン）−Ｄ−α−ア
ミノオキシブチリル一Ｎ′−イソニコチノイルーヒドラ
ジンＤ−α−アミノオキシ酪酸塩酸塩３．１０ｇ（０．
０２０モル）を水７．０ｄ中に溶解し、この溶液に酢酸
ナトリウム１．６４９（０．０２０モル）を添加した。Example 1 N-(N″-5-nitrofurfurylidene)-D-α-aminooxybutyryl-N′-isonicotinoylhydrazine D-α-aminooxybutyric acid hydrochloride 3.10 g (0.
020 mol) was dissolved in 7.0 d of water and 1.649 (0.020 mol) of sodium acetate was added to this solution.

この混合物にメタノール１０．０７１Ｌｔ中の５−ニト
ロフルフロール２．８４９（０．０２０モル）の溶液を
攪拌下に室温で滴加した。反応混合物を室温で１６時間
放置し、ついで水２３．０ｄを添加した。析出した生成
物を戸別し、乾燥し、酢酸エチルから再結晶してＤ−α
−Ｎ−（５−ニトロフルフリリデン）−アミノオキシ酪
酸２．１２９（８８％）を得た。融点：１１７〜１１８
℃（酢酸エチルから再結晶後），Ｒｆ＝０．７７，〔α
〕智＝＋３４″（ｃ＝１，１エタノール中）。元素分析
： 計算値（Ｃ，ＨｌＯＯ６Ｎ２）： Ｃ，４４．７％ Ｈ，４．ｌ％ Ｎ，ｌｌ．６％実測値
：Ｃ，４４．８％ Ｈ，４．Ｏ％ Ｎ，ｌｌ．６％Ｄ−
α−Ｎ−（５−ニトロフルフリリデン）−アミノオキシ
酪酸１．０９（０．００４１２モル）、イソニコチン酸
ヒドラジド０．５５９（０．００４モル）、Ｎ，マージ
シクロヘキシル カルボジイミド ０．８５９（０．０
０４１２モル）及び無水ジメチルホルムアミド１０．０
ｍｔの混合物を室温で１６時間攪拌した。A solution of 2.849 (0.020 mol) of 5-nitrofurfurol in 10.071 Lt of methanol was added dropwise to this mixture at room temperature while stirring. The reaction mixture was left at room temperature for 16 hours, then 23.0 d of water was added. The precipitated product was separated, dried, and recrystallized from ethyl acetate to obtain D-α.
2.129 (88%) of -N-(5-nitrofurfurylidene)-aminooxybutyric acid was obtained. Melting point: 117-118
°C (after recrystallization from ethyl acetate), Rf = 0.77, [α
] Chi=+34″ (c=1,1 in ethanol). Elemental analysis: Calculated value (C, HlOO6N2): C, 44.7% H, 4.1% N, ll.6% Actual value: C, 44 .8% H, 4.O% N, 1.6% D-
α-N-(5-nitrofurfurylidene)-aminooxybutyric acid 1.09 (0.00412 mol), isonicotinic acid hydrazide 0.559 (0.004 mol), N,merized cyclohexyl carbodiimide 0.859 (0. 0
0412 mol) and anhydrous dimethylformamide 10.0
The mt mixture was stirred at room temperature for 16 hours.

析出したＮ，Ｎ′−ジシクロヘキシル尿素をＰ別し、Ｐ
液を減圧下で蒸発乾固した。残渣を１Ｎｆ１Ｌｒｉｔ１
５ｄ中溶解し、この溶液を酢酸エチル３Ｘ５ｄで抽出し
た。水相を固体炭酸水素ナトリウムでＰＨ＝７まで中和
し、析出物をＰ別し、水洗いし、エタノール５０９ｂと
水との混合物から再結晶して標題化合物０．９６ｆ１（
６９（Ｆｂ）を得た。融点：１６４〜１６６０Ｃ，Ｒｆ
＝０．１５，〔α〕Ｍ＝＋１３２４（ｃ＝１、エタノー
ル中）。元素分析：計算値（Ｃｌ５Ｈ，ｌＯ６Ｎ，）： Ｃ，４９．２％ Ｈ，４．３％ Ｎ，２Ｏ．Ｏ％実測値
：Ｃ，４９．３％ Ｈ，４．４（！） Ｎ，ｌ９．９（
Ｆｂ実施例 ２Ｎ−（Ｎ″−５−ニトロフルフリリデン
）−Ｄα−アミノオキシ−ｒ−メチルーメルカブトーブ
チリル一Ｎ′−イソニコチノイルーヒドラジン標題化合
物を適当な出発物質を用いて実施例１と同様に製造した
。The precipitated N,N'-dicyclohexyl urea was separated from P and P
The liquid was evaporated to dryness under reduced pressure. The residue is 1Nf1Lrit1
The solution was extracted with 3×5 d of ethyl acetate. The aqueous phase was neutralized with solid sodium bicarbonate to pH=7, the precipitate was separated from P, washed with water, and recrystallized from a mixture of ethanol 509b and water to yield the title compound 0.96f1 (
69 (Fb) was obtained. Melting point: 164-1660C, Rf
=0.15, [α]M=+1324 (c=1, in ethanol). Elemental analysis: Calculated values (Cl5H, 1O6N,): C, 49.2% H, 4.3% N, 2O. O% actual value: C, 49.3% H, 4.4 (!) N, l9.9 (
Fb Example 2N-(N″-5-nitrofurfurylidene)-Dα-aminooxy-r-methyl-mercabutobutyryl-N′-isonicotinoylhydrazine Example 2 Preparation of the title compound using appropriate starting materials It was manufactured in the same manner as 1.

収率７０％：融点１３０〜１３５℃（酢酸エチルから再
結晶後）：Ｒｆ＝０．１７：〔α〕Ｍ＝＋８９結（ｃ＝
１、エタノール中）。元素分析： 計算値（Ｃｌ６Ｈ，，Ｏ５Ｎ，Ｓ）： Ｃ，４７．２％ Ｈ，４．２（ＦｂＮ，ｌ７．２％実測
値：Ｃ，４７．２％ Ｈ，４．３％ Ｎ，ｌ７．ｌ％出
発物質としてのＤ−α−Ｎ−（５−ニトロフルフリリデ
ン）−アミノオキシ−ｒ−メチルメルカプト酪酸を実施
例１と同様に製造し、この化合物をより良好な取扱い適
性を確保するためにそのシンクロヘキシルアンモニウム
塩に転化した。Yield 70%: Melting point 130-135°C (after recrystallization from ethyl acetate): Rf = 0.17: [α] M = +89 (c =
1 in ethanol). Elemental analysis: Calculated value (Cl6H,,O5N,S): C, 47.2% H, 4.2 (FbN, l7.2% Actual value: C, 47.2% H, 4.3% N, l7 D-α-N-(5-nitrofurfurylidene)-aminooxy-r-methylmercaptobutyric acid as starting material is prepared analogously to Example 1 to ensure better handling suitability of this compound. It was converted into its synchhexylammonium salt for the purpose.

得られた塩は使用前にそれ自体既知の方法により酸の形
に遊離させる。生成物の融点：１５８〜１５９℃。元素
分析： 計算値（Ｃ２２Ｈ３，Ｏ，Ｎ，Ｓ）： Ｃ，５６．３（ＦｂＨ，７．５％ Ｎ，９．Ｏ（Ｆｂ実
測値：Ｃ，５６．３％ Ｈ，７．４％ Ｎ，９．ｌ（Ｆ
ｂ実施例 ３Ｎ−（Ｎ′５−５−ニトロフルフリリデン
）−Ｄ一α−アミノオキシ−β−フエニループロピオニ
ル一Ｎ′−イソニコチノイルーヒ下ラジン塩酸塩Ｄ−α
−アミノオキシ−β−フエニループロピオン酸塩酸塩２
．１７９（０．０１０モル）と５−ニトロフルフロール
１．４２９（０．０１０モル）とを実施例１の前半と同
様にして反応させてＤ−α一Ｎ−（５−ニトロフルフリ
リデン）−アミノオキシ−β−フエニループロピオン酸
２．７５ｆ１（９１９ｂ）を得た。The salts obtained are liberated into the acid form by methods known per se before use. Melting point of product: 158-159°C. Elemental analysis: Calculated values (C22H3, O, N, S): C, 56.3 (FbH, 7.5% N, 9.O (Fb actual values: C, 56.3% H, 7.4% N) ,9.l(F
b Example 3N-(N'5-5-nitrofurfurylidene)-D-α-aminooxy-β-phenylpropionyl-N'-isonicotinoyl-Razine hydrochloride D-α
-Aminooxy-β-phenylpropionate hydrochloride 2
．． 179 (0.010 mol) and 5-nitrofurfurol 1.429 (0.010 mol) were reacted in the same manner as in the first half of Example 1 to obtain D-α-N-(5-nitrofurfurylidene)- Aminooxy-β-phenylpropionic acid 2.75f1 (919b) was obtained.

融点：１５６〜１５８℃：Ｒｆ＝０．５２：〔α〕智＝
−８６（ｃ＝０．６，エタノール中）。元素分析： 言十ｊ家イ直（ Ｃｌ４Ｈｌ２Ｏ６Ｎ２）：Ｃ，５５．
２％ Ｈ，４．Ｏ％ Ｎ，９．２％実測値：Ｃ，５５．
２％ Ｈ，４．ｌ％ Ｎ，９．ｌ％Ｄ−α−Ｎ−（５−
ニトロフルフリリデン）アミノオキシ一β−フエニルー
プロピオン酸１．０ｆ１（０．００４６モル）、ペンタ
クロロフエノール１．２２９（０．００４６モル）及び
Ｎ，Ｎ′−ジシクロヘキシルカルボジイミド０．９５ｆ
ｉ・（０．００４６モル）をジオキサン１０．０ｄ中に
撹拌下室温で溶解した。Melting point: 156-158°C: Rf = 0.52: [α] Wisdom =
-86 (c=0.6, in ethanol). Elemental analysis: Cl4Hl2O6N2: C, 55.
2% H, 4. O% N, 9.2% Actual value: C, 55.
2% H, 4. 1% N,9. l%D-α-N-(5-
Nitrofurfurylidene) aminooxy-β-phenylpropionic acid 1.0f1 (0.0046 mol), pentachlorophenol 1.229 (0.0046 mol) and N,N'-dicyclohexylcarbodiimide 0.95f
i. (0.0046 mol) was dissolved in 10.0 d of dioxane at room temperature with stirring.

この反応混合物を室温で１６時間放置し、析出したＮ，
Ｎ′−ジシクロヘキシル尿素を戸別し、淵液を減圧下で
蒸発乾固した。残渣をエタノールと水との８：２混合物
から再結晶してＤ−α−Ｎ−（５−ニトロフルフリリデ
ン）−アミノオキシ−β−フエニループロピオン酸ペン
タクロロフエニルエステル２．１２９（８３％）を得ム
融点：１６４〜１６５℃：Ｒｆ＝０．７７：〔α席＝＋
１３４〜（ｃ＝１、エタノール中）。元素分析： 計算値（Ｃ２ＯＨ，ｌＯ，Ｎ２Ｃｌ，）：Ｃ，４３．５
Ｏ！） Ｈ，２．Ｏ％ Ｃｅ，３２．Ｏ％実御値：Ｃ，
４３．６％ Ｈ，２．ｌ％ Ｃｌ，３ｌ．９％Ｄ−α−
Ｎ−（５−ニトロフルフリリデン）−アミノオキシ−β
−フエニループロピオン酸ペンタクロロフエニル エス
テル１．０ｆ１（０．００１８モル）及びイソニコチン
酸ヒドラジド０．２５ｆ！（０．００１８モル）を無水
ジメチルホルムアミド１０．０ＴＩＬＩ中に溶解し、こ
の溶液を室温で６時間撹拌した。This reaction mixture was left at room temperature for 16 hours, and the precipitated N,
N'-dicyclohexylurea was separated and the bottom liquid was evaporated to dryness under reduced pressure. The residue was recrystallized from an 8:2 mixture of ethanol and water to give D-α-N-(5-nitrofurfurylidene)-aminooxy-β-phenyl-propionic acid pentachlorophenyl ester 2.129 (83%). Melting point: 164-165℃: Rf = 0.77: [α seat = +
134~(c=1 in ethanol). Elemental analysis: Calculated value (C2OH, lO, N2Cl,): C, 43.5
O! ) H, 2. O% Ce, 32. O% actual value: C,
43.6% H, 2. 1% Cl, 3l. 9%D-α-
N-(5-nitrofurfurylidene)-aminooxy-β
-Phenyl-propionate pentachlorophenyl ester 1.0f1 (0.0018 mol) and isonicotinic acid hydrazide 0.25f! (0.0018 mol) was dissolved in 10.0 TILI of anhydrous dimethylformamide and the solution was stirred at room temperature for 6 hours.

ついで反応混合物を減圧下で蒸発乾固した。残渣を酢酸
エチル１０１ＬＩ，中に溶解し、１Ｍ炭酸水素ナトリウ
ム溶液３Ｘ５ｍ１、ついで水２Ｘ５ｄで洗浄した。有機
相を硫酸ナトリウムで乾燥し、溶剤を減圧留去した。残
渣を０．５Ｎエーテル性塩酸２０７ｎ１で処理し、析出
した塩を戸別し、熱エタノール中に溶解し、冷却後ジエ
チル エーテルを加えた溶液から沈澱させた。かくして
Ｎ−（Ｎ′５−５−ニトロフルフリリデシ）一Ｄ−α−
アミノオキシ−β−フエニループロピオニルーマーイソ
ニコチノイルーヒドラジ７塩酸塩０．６４ｇ（８１％）
を得た。The reaction mixture was then evaporated to dryness under reduced pressure. The residue was dissolved in 101 LI of ethyl acetate and washed with 3.times.5 ml of 1M sodium bicarbonate solution and then 2.times.5 ml of water. The organic phase was dried over sodium sulfate and the solvent was distilled off under reduced pressure. The residue was treated with 207 nl of 0.5N ethereal hydrochloric acid, and the precipitated salt was separated, dissolved in hot ethanol and, after cooling, precipitated from the solution with diethyl ether. Thus, N-(N'5-5-nitrofurfurylidecy)-D-α-
Aminooxy-β-phenylpropionyl lumer isonicotinoyl hydrazi heptahydrochloride 0.64g (81%)
I got it.

融点：７５〜７６℃；Ｒｆ＝０．０８：〔α〕＝＋８６
：（ｃ＝１、工タノール中）。元素分析： 計算値（Ｃ，。Melting point: 75-76°C; Rf = 0.08: [α] = +86
: (c=1, in ethanol). Elemental analysis: Calculated values (C,.

Ｈ，８Ｎ，ＣＯ：Ｃ，５２．３％ Ｈ，３．９％ Ｃｅ
，７．７％実測値：Ｃ，５２．２（ＦｂＨ，４．Ｏ％
Ｃｌ，７．７％実施例１〜３と同様にして適当な出発物
質から下記の化合物を製造した。H, 8N, CO:C, 52.3% H, 3.9% Ce
, 7.7% Actual value: C, 52.2 (FbH, 4.O%
Cl, 7.7% The following compounds were prepared from the appropriate starting materials in a similar manner to Examples 1-3.

実施例 ４ Ｎ−（Ｎ″−ｍ−ニトローベンザル）−アミノオキシア
セチル−Ｎ′−イソニコチノイルーヒドラジン融点：１
５８〜１６０℃（エタノールから再結晶後）元素分析： 計算値（ＣＯＨ，，Ｏ，Ｎ，）： Ｃ，５２．５９ｂＨ，３．８％ Ｎ，２Ｏ．４％実二１
・゛ ゛Ｃ，５２．５！ＦｂＨ，３，９（！）Ｎ，２
Ｏ．５％実施例 ５Ｎ−（Ｎ２−１−メチル−ｐ−アミ
ノーベンザル）−アミノオキシアセチル−Ｎ′−イソニ
コチノイルーヒドラジン融点：１７５〜１７７℃（エタ
ノールから再結晶後）
Ｃ元素分析：計算値（ＣｌＩＨｌ？０，Ｎ
．）： ゛コＣｔ５＆フ％ Ｈ，５．２９ｈＮ，２ｌ．４％実棚
値； ゛７Ｃ，５８．▼％ Ｈ：１２％Ｎ，２
ｌ．２％ ；実施例 ６Ｎ−（Ｎ″−ｐ−ヒドロキシー
ベンザル）−アミノオキシアセチル−Ｎ′−イソニコチ
ノイルーヒドラジンし゜融点：２０３〜２０４℃（エタ
ノールから再結 ＦＭ）元素分析： 計算値（ＣｌＨｉＯ，Ｓｌ）： Ｃ，５７．４％ Ｈ・，４Ｊ・１ｆｂＮ，１７．８９ｉ
実測値：Ｃ，５７．５％ Ｈ，４．６％ Ｎ，ｌ７．８
％実施例 ７Ｎ−（Ｎ″−０−クロローベンザル）−ア
ミノオキシアセチル−Ｎ′−イソニコチノイルーヒドラ
ジン融点：１４７〜１４９℃（エタノールから再結晶後
）元素分析： 計算値（Ｃｌ６Ｈ，３Ｏ，Ｎ４Ｃｌ）： Ｃ，５４．ｌ％ Ｈ，３．９％ Ｃ２，ｌＯ．７％実測
値：Ｃ，５４．Ｏ％ Ｈ，４．Ｏ％ Ｃｅ，・１０．７
％実施例 ８Ｎ−（Ｎ′５−シクロペンチリデン）−ア
ミノオキシアセチル−Ｎ′−イソニコチノイルーヒドラ
ジン融点：１６０〜１６１℃（水から再結晶後）元素分
析：計算値（Ｃ，，Ｈｌ６Ｏ，Ｎ４）： Ｃ，５６．５％ Ｈ，５．８％ Ｎ，２Ｏ．３％実測値
：Ｃ，５６．５％ Ｈ，５．８％ Ｎ，２Ｏ．ｌ％実施
例 ９Ｎ−（Ｎ′５−フルフリリデン）−アミノオキシ
アセチル−Ｎ′−イソニコチノイルービドラジン融点：
１２３〜１２５℃（水から再結晶後）元素分析：計算値
（Ｃ，，Ｈ，，Ｏ４Ｎ４）： Ｃ，５４．ｌ％ Ｈ，４．２％ Ｎ，ｌ９．４％実測値
：Ｃ，５４．２％ Ｈ，４．３ｌｆｂＮ，ｌ９．４％実
施例 １０Ｎ−（Ｎ″−１−メチルーベンザル）−アミ
ノオキシアセチル−Ｗ−イソニコチノイｊソレーヒドラ
ジン融点：１６０〜１６２℃（エタノールから再結晶後
）元素分析： 計算値（Ｃ，，Ｈ，。Example 4 N-(N″-m-nitrobenzal)-aminooxyacetyl-N′-isonicotinoylhydrazine Melting point: 1
58-160°C (after recrystallization from ethanol) Elemental analysis: Calculated values (COH,,O,N,): C, 52.59bH, 3.8% N, 2O. 4% real 21
・゛ ゛C, 52.5! FbH,3,9(!)N,2
O. 5% Example 5N-(N2-1-methyl-p-aminobenzal)-aminooxyacetyl-N'-isonicotinoylhydrazine Melting point: 175-177°C (after recrystallization from ethanol)
C elemental analysis: Calculated value (ClIHl?0,N
．． ): ゛CoCt5&F%H, 5.29hN, 2l. 4% actual shelf value; ゛7C, 58. ▼%H:12%N,2
l. 2%; Example 6 N-(N″-p-hydroxybenzal)-aminooxyacetyl-N′-isonicotinoylhydrazine Melting point: 203-204°C (reconsolidated from ethanol FM) Elemental analysis: Calculated value (ClHiO, Sl): C, 57.4% H, 4J, 1fbN, 17.89i
Actual value: C, 57.5% H, 4.6% N, l7.8
% Example 7 N-(N″-0-chlorobenzal)-aminooxyacetyl-N′-isonicotinoylhydrazine Melting point: 147-149°C (after recrystallization from ethanol) Elemental analysis: Calculated value (Cl6H,3O,N4Cl ): C, 54.1% H, 3.9% C2, 1O.7% Actual value: C, 54.0% H, 4.0% Ce, ・10.7
% Example 8 N-(N'5-cyclopentylidene)-aminooxyacetyl-N'-isonicotinoylhydrazine Melting point: 160-161°C (after recrystallization from water) Elemental analysis: Calculated value (C,, Hl6O , N4): C, 56.5% H, 5.8% N, 2O. 3% actual value: C, 56.5% H, 5.8% N, 2O. 1% Example 9 N-(N'5-furfurylidene)-aminooxyacetyl-N'-isonicotinoyl-hydrazine Melting point:
123-125°C (after recrystallization from water) Elemental analysis: Calculated value (C,,H,,O4N4): C, 54. 1% H, 4.2% N, 19.4% Actual value: C, 54.2% H, 4.3lfbN, 19.4% Example 10 N-(N″-1-methyl-benzal)-aminooxy Acetyl-W-Isonicotinoidj Solehydrazine Melting point: 160-162°C (after recrystallization from ethanol) Elemental analysis: Calculated value (C,,H,.

Ｏ，Ｎ，）：Ｃ，６ｌ．５％ Ｈ，５．ｌ％ Ｎ，ｌ８
．Ｏ％実測値：Ｃ，６ｌ．４％ Ｈ，５．３％ Ｎ，ｌ
８．２実施例 １１ Ｎ−（Ｎ″−シクロペンチリデン）−Ｄ−α−アミノオ
キシ−β−フエニループロピオニル一Ｎ′ーイソニコチ
ノイルーヒドラジン融点：１９１〜１９４℃（水性エタ
ノールから再結晶後），〔α〕Ｒ＝７１性（Ｃ＝１，エ
タノール中）。O, N, ): C, 6l. 5% H,5. 1% N, 18
．． O% actual value: C, 6l. 4% H, 5.3% N, l
8.2 Example 11 N-(N″-cyclopentylidene)-D-α-aminooxy-β-phenylpropionyl-N′-isonicotinoylhydrazine Melting point: 191-194°C (recrystallized from aqueous ethanol) after), [α]R=71 (C=1, in ethanol).

元素分析： 計算値（Ｃ２ＯＨ２，Ｏ３Ｎ４）： Ｃ，６５．６％ Ｈ，６．ｌ％ Ｎ，ｌ５．３％実側値
： Ｃ，６５．５ＣｆｂＨ，６、２％ Ｎ，ｌ５．３％実施
例 １２ Ｎ−（Ｎ７′−ｍ−ニトローベンザル）−Ｄ−α−アミ
ノオキシ−β−フエニループロピオニルー一Ｎ′−イソ
ニコチノイルーヒドラジン塩酸塩融点：７６〜７８チｃ
，〔α〕Ｍ＝＋７２酸（ｃ＝１、エタノール中）。Elemental analysis: Calculated values (C2OH2, O3N4): C, 65.6% H, 6. 1% N, 15.3% Actual value: C, 65.5CfbH, 6, 2% N, 15.3% Example 12 N-(N7'-m-nitrobenzal)-D-α-aminooxy-β -Phenyl-propionyl-N'-isonicotinoyl-hydrazine hydrochloride Melting point: 76-78 c
, [α]M=+72 acid (c=1, in ethanol).

元素分析： 計算値（Ｃ２２Ｈ，ＯＯ，Ｎ，ｃｅ）： Ｃ，５６．３％ Ｈ，４．３％ Ｃ２，７．５９）実測
値： Ｃ，５６．３９ｌ） Ｈ，゛４．４％ Ｃｌ，７．４％
実施例 １３ Ｎ−（Ｎ″−５−ニトロフルフリリデン）−アミノオキ
シアセチル−Ｎ′−イソニコチノイルーヒドラジン融点
：１６８〜１７０℃（水から再結晶化後）＜元素分析：
計算値（Ｃｌ３ＨｌｌＯ，Ｎ，）：Ｃ，４６．９％ Ｈ
，３．３９ｂＮ，２ｌ．Ｏ％実測値： Ｃ，４６．８％ Ｈ，３，３％ Ｎ，２ｌ．Ｏ９ｂ実施
例 １４ Ｎ−（Ｎ′５−イソプロピリデン）−アミノオキシアセ
チル−Ｎ′−イソニコチノイルーヒドラジン融点：１３
５〜１３６℃０ 元素分析： 計算値（Ｃ，ｌＨ，４Ｏ，Ｎ４）： Ｃ，５２．８％ Ｈ，５．６（ＦｂＮ，２２．４％実測
値： Ｃ，５２．７％ Ｈ，５．７％ Ｎ，２２．４％この化
合物０．５０９を氷酢酸中の臭化水素の３６％溶液２．
０Ｗ１１中に溶解し、形成された塩を無水ジエチルエー
テル１０，０ｄを加えて沈澱させてその臭化水素酸塩０
，６３９（９６％）を得た。Elemental analysis: Calculated value (C22H, OO, N, ce): C, 56.3% H, 4.3% C2, 7.59) Actual value: C, 56.39l) H, 4.4% Cl ,7.4%
Example 13 N-(N″-5-nitrofurfurylidene)-aminooxyacetyl-N′-isonicotinoylhydrazine Melting point: 168-170°C (after recrystallization from water) <Elemental analysis:
Calculated value (Cl3HllO, N,): C, 46.9% H
, 3.39bN, 2l. O% actual value: C, 46.8% H, 3.3% N, 2l. O9b Example 14 N-(N'5-isopropylidene)-aminooxyacetyl-N'-isonicotinoylhydrazine Melting point: 13
5-136°C 0 Elemental analysis: Calculated value (C, lH, 4O, N4): C, 52.8% H, 5.6 (FbN, 22.4% Actual value: C, 52.7% H, 5 .7% N, 22.4% This compound was dissolved in a 36% solution of hydrogen bromide in glacial acetic acid.
0W11 and the salt formed was precipitated by adding 10.0d of anhydrous diethyl ether to obtain its hydrobromide salt.
,639 (96%).

融点：１５２℃，Ｒｆ＝０．０７。Melting point: 152°C, Rf=0.07.

元素分析： 計算値（Ｃｌ，Ｈｌ，Ｏ３Ｎ４Ｂｒ）： Ｃ，３９．９Ｏｌ） Ｈ，４．５％ Ｂｒ，２４．８９
ｂ実測値： Ｃ，３９．８％ Ｈ，４．６％ Ｂｒ，２４．９％。Elemental analysis: Calculated values (Cl, Hl, O3N4Br): C, 39.9Ol) H, 4.5% Br, 24.89
b Actual values: C, 39.8% H, 4.6% Br, 24.9%.

Claims (1)

【特許請求の範囲】 １ 一般式（II）： ▲数式、化学式、表等があります▼（II）（式中、Ｘ及
びＲは後記の意義を有し：Ｒ′は水素、炭素数１〜５個
のアルキル基あるいは１個又は２個以上のハロゲン又は
ニトロ置換基を有するフェニル基である）のシッフ塩基
を式（III）：Ｈ＿２Ｎ−ＮＨＺ（III）（式中、Ｚはピ
リジンカルボン酸から誘導されるアシル基である）のヒ
ドラジン誘導体と反応させ、ついで所望ならば、得られ
た塩基を常法によりその酸付加塩に転化するかあるいは
得られた塩を常法によりその遊離塩基又は別の塩に転化
することからなる式（ I ）：▲数式、化学式、表等が
あります▼（ I ）（式中、Ｘはシクロペンチリデン基
あるいは炭素数１〜５個のアルキル、フェニル、ハロフ
エニル、ヒドロキシフェニル、ニトロフェニル、アミノ
フェニル、フリル及びニトロフリル基から選んだ少なく
とも１個の置換基を有するメチレン基を表わし；Ｒは水
素、ベンジル基又は随意にメチルチオ置換基を有する炭
素数１〜５個のアルキル基を表わし；Ｚはピリジンカル
ボン酸から誘導されたアシル基を表わす）の化合物又は
その酸付加塩の製造法。[Claims] 1 General formula (II): ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (II) (In the formula, X and R have the meanings below: R' is hydrogen, carbon number 1- 5 alkyl groups or a phenyl group having one or more halogen or nitro substituents) with the formula (III): H_2N-NHZ(III) (wherein Z is from pyridinecarboxylic acid) the hydrazine derivative (which is the acyl group to be derived) and then, if desired, the resulting base is converted into its acid addition salt by conventional methods or the resulting salt is converted into its free base or another salt by conventional methods. Formula (I): ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (I) (wherein, Represents a methylene group having at least one substituent selected from hydroxyphenyl, nitrophenyl, aminophenyl, furyl and nitrofuryl; R is hydrogen, a benzyl group, or a carbon number of 1 to 5, optionally having a methylthio substituent represents an alkyl group; Z represents an acyl group derived from pyridinecarboxylic acid) or an acid addition salt thereof.
JP57052368A 1973-11-29 1982-04-01 Method for producing novel α-aminooxycarboxylic acid hydrazide derivative Expired JPS5953264B2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
HU530 1973-11-29
HURI530A HU167365B (en) 1973-11-29 1973-11-29

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JPS5953264B2 true JPS5953264B2 (en) 1984-12-24

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AT (1) AT340920B (en)
BE (1) BE822767A (en)
CA (1) CA1018171A (en)
CH (2) CH614954A5 (en)
CS (1) CS199568B2 (en)
DD (1) DD118874A5 (en)
DE (1) DE2455353C3 (en)
FR (1) FR2252845B1 (en)
GB (1) GB1446980A (en)
HU (1) HU167365B (en)
NL (1) NL7415589A (en)
SU (2) SU574146A3 (en)

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* Cited by examiner, † Cited by third party
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ATE52765T1 (en) * 1984-10-18 1990-06-15 Shell Int Research ALPHA AMINOOXY C4 ALKANOIC ACIDS AND ESTERS.
JPH0317434Y2 (en) * 1986-03-11 1991-04-12
US5002605A (en) * 1988-12-21 1991-03-26 Ici Americas Inc. Alkylidine aminooxyamide compounds useful in controlling undesirable vegetation
BRPI0509282A (en) 2004-03-30 2007-09-18 Univ California cftr inhibitor hydrazide containing compounds and their uses
CA2671900A1 (en) 2006-12-22 2008-07-03 The Regents Of The University Of California Macromolecular conjugates of cystic fibrosis transmembrane conductance regulator protein inhibitors and uses thereof
US8283351B2 (en) 2007-04-02 2012-10-09 Institute For Oneworld Health Cyclic and acyclic hydrazine derivatives compositions including them and uses thereof
WO2008150470A1 (en) 2007-05-31 2008-12-11 Shionogi & Co., Ltd. Oxyimino compounds and the use thereof
JP5380435B2 (en) * 2007-05-31 2014-01-08 ユーロ−セルティーク ソシエテ アノニム Amide compounds and uses thereof
WO2009131951A2 (en) 2008-04-21 2009-10-29 Institute For Oneworld Health Compounds, compositions and methods comprising isoxazole derivatives
US8207205B2 (en) 2008-04-21 2012-06-26 Institute For Oneworld Health Compounds, compositions and methods comprising oxadiazole derivatives
US8518934B2 (en) 2008-06-11 2013-08-27 Shonogi & Co., Ltd. Oxycarbamoyl compounds and the use thereof
US8343976B2 (en) 2009-04-20 2013-01-01 Institute For Oneworld Health Compounds, compositions and methods comprising pyrazole derivatives
CN102276593B (en) * 2011-07-01 2013-10-30 华东师范大学 Heterocyclic ketene hydrazone compound and preparation method as well as tubercle bacillus resistant application
WO2014201446A2 (en) * 2013-06-14 2014-12-18 Hellmich Mark Use of hydrogen sulfide synthesis inhibitors for the therapy of colorectal cancers

Also Published As

Publication number Publication date
JPS5084523A (en) 1975-07-08
DE2455353C3 (en) 1979-08-09
CS199568B2 (en) 1980-07-31
JPS5951537B2 (en) 1984-12-14
FR2252845A1 (en) 1975-06-27
DD118874A5 (en) 1976-03-20
AT340920B (en) 1978-01-10
CA1018171A (en) 1977-09-27
CH612926A5 (en) 1979-08-31
GB1446980A (en) 1976-08-18
DE2455353A1 (en) 1975-06-05
CH614954A5 (en) 1979-12-28
FR2252845B1 (en) 1978-07-21
NL7415589A (en) 1975-06-02
SU574146A3 (en) 1977-09-25
ATA940574A (en) 1977-05-15
BE822767A (en) 1975-03-14
JPS57192365A (en) 1982-11-26
DE2455353B2 (en) 1978-12-07
SU608472A3 (en) 1978-05-25
HU167365B (en) 1975-09-27

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