JP2017505307A - 抗真菌組成物 - Google Patents
抗真菌組成物 Download PDFInfo
- Publication number
- JP2017505307A JP2017505307A JP2016548106A JP2016548106A JP2017505307A JP 2017505307 A JP2017505307 A JP 2017505307A JP 2016548106 A JP2016548106 A JP 2016548106A JP 2016548106 A JP2016548106 A JP 2016548106A JP 2017505307 A JP2017505307 A JP 2017505307A
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- antifungal
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- atoms
- antifungal composition
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Classifications
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- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N35/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical
- A01N35/04—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical containing aldehyde or keto groups, or thio analogues thereof, directly attached to an aromatic ring system, e.g. acetophenone; Derivatives thereof, e.g. acetals
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- A—HUMAN NECESSITIES
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- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/44—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
- A01N37/46—N-acyl derivatives
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- A—HUMAN NECESSITIES
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- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
- A01N43/647—Triazoles; Hydrogenated triazoles
- A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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- A—HUMAN NECESSITIES
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- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
- A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
- A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
- A01N47/20—N-Aryl derivatives thereof
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
- A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
- A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
- A01N47/24—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof containing the groups, or; Thio analogues thereof
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- A—HUMAN NECESSITIES
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- A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
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Abstract
Description
R2が、水素またはヒドロキシ基または1〜3個のC原子を有するアルコキシ基であり、
R3が、C1〜C4アルキル基で一置換または多置換されていてもよい、4〜20個のC原子を有する直鎖または分岐のアルキルまたはアルキレンであり、
R4が、水素またはヒドロキシ基または1〜3個のC原子を有するアルコキシ基であり、
R5が、ハロゲン基であり、かつ
R6が、HまたはC1〜C4アルキル基であり、
但し、R2およびR4のうち少なくとも一方が、ヒドロキシ基または1〜3個のC原子を有するアルコキシ基である。
R1は、CHO、CH2OH、CN、CH3、C(O)NH2、C(O)NHCH3、C(O)CH3、CF2CH3、CH2CH3、CH2OAc、COOH、およびCOOCH3から選択され、かつ
R2は、ヒドロキシル基であり、
R3は、C1〜C4アルキル基で一置換または多置換されていてもよい、4〜20個のC原子を有する直鎖または分岐のアルキルまたはアルキレンであり、
R4は、ヒドロキシル基であり、
R5は、塩素原子であり、
R6は、HまたはC1〜C4アルキル基である。
R1は、CHO、CH2OH、CN、CH3、C(O)NH2、C(O)NHCH3、C(O)CH3、CF2CH3、CH2CH3、CH2OAc、COOH、およびCOOCH3から選択され、かつ
R2は、ヒドロキシル基であり、
R3は、C1〜C2アルキル基で一置換または多置換されていてもよい、6〜15個のC原子を有する直鎖または分岐のアルキルまたはアルキレンであり、
R4は、ヒドロキシル基であり、
R5は、塩素原子であり、
R6は、HまたはC1〜C4アルキル基である。
R1は、CHO、CH2OH、CN、CH3、C(O)NH2、C(O)NHCH3、C(O)CH3、CF2CH3、CH2CH3、CH2OAc、COOH、およびCOOCH3から選択され、かつ
R2は、ヒドロキシル基であり、
R3は、8〜10個のC原子を有するアルキレン鎖であり、かつ少なくとも1つのメチル基、好ましくは少なくとも2つのメチル基で置換されており、
R4は、ヒドロキシル基であり、
R5は、塩素原子であり、
R6は、メチル基である。
R1は、CHOであり、
R2は、ヒドロキシル基であり、
R3は、8〜10個のC原子を有するアルキレン鎖であり、かつ少なくとも1つのメチル基、好ましくは少なくとも2つのメチル基で置換されており、
R4は、ヒドロキシル基であり、
R5は、塩素原子であり、
R6は、メチル基である。この式Iを有する化合物は、図1に表されるコレトクロリンBとして知られることが理解されるであろう。
R2が、水素またはヒドロキシ基または1〜3個のC原子を有するアルコキシ基であり、
R3が、C1〜C4アルキル基で一置換または多置換されていてもよい、4〜20個のC原子を有する直鎖または分岐のアルキルまたはアルキレンであり、
R4が、水素またはヒドロキシ基または1〜3個のC原子を有するアルコキシ基であり、
R5が、ハロゲン基であり、かつ
R6が、HまたはC1〜C4アルキル基であり、
但し、R2およびR4のうち少なくとも一方が、ヒドロキシ基または1〜3個のC原子を有するアルコキシ基である。
[材料]
YPD培地/寒天
○2%酵母抽出物
○2%ペプトン
○2%D−グルコース
○2%寒天
YPG
○2%酵母抽出物
○2%ペプトン
○2%グリセロール
○2%寒天。
国際公開第2013/160670号に記載される方法論を使用して、図7を参照しながら、コレトクロリンBを合成する。その後、1μMコレトクロリンBを、5μMの以下の各殺真菌薬と別個に組み合わせて、7種類の異なる製剤を生成する。
2)アゾキシストロビン−ストロビルリンファミリーに属する;
3)DMI(脱メチル化阻害剤);
4)CuPC33(銅系化合物);
5)ボスカリド;
6)ジフェンコンコゾール;および
7)ピラクロストロビン。
1.酵母株をYPD寒天プレート上に画線し、その上で、30℃で3日間増殖させる:
2.5mLのYPD液体培地に、対象となる真菌株(例えば、クララ・フラキシニア)を植菌し、180rpmで振盪させながら、30℃で3日間増殖させる:
3.真菌株の1μLの種菌を、9999μLのYPG液体培地に添加し、穏やかに混合する:
4.その後、1μMコレクトクロリンBおよび5μM殺真菌薬を含む7種類の製剤それぞれについて異なる阻害剤濃度範囲(例えば1μM、1.5μMおよび2μM)を含むYPG寒天プレート上に置く:
5.プレートを、30℃で3〜5日間増殖させる:
6.その後、阻害剤によって引き起こされる真菌/酵母増殖の阻害の程度を評価する。
驚くべきことに、本発明者らは、7種類の組み合わせ製剤それぞれについて、相乗的阻害が見られることを観察した。例えば、本発明者らは、コレトクロリンBおよびアゾキシストロビンを、クララ・フラキシニアに対して、個別におよび組み合わせで試験した。化合物が別個に使用されるとき、真菌の部分的な増殖阻害が見られる。しかしながら、組み合わせで使用されるとき、完全な阻害が見られる。したがって、本発明者らは、化合物I(好ましくは、コレトクロリンB)および様々な他の抗真菌化合物を含む7種類の製剤が、真菌感染症を治療または予防するために有効に使用され得ると考える。
本発明者らは、出芽酵母(S. cerevisiae)の増殖に対する、コレトクロリンBとアゾキシストロビンとの組み合わせの有効性を試験した。実施例1のように、国際公開第2013/160670号に記載される方法論を使用して、図7を参照しながら、コレトクロリンBを合成した。
1.出芽酵母をYPD寒天プレート上に画線し、その上で、30℃で3日間増殖させる:
2.5mLのYPG液体培地に、YPDプレートから出芽酵母を植菌し、180rpmで振盪させながら、30℃で3日間増殖させて、細胞培養物を生成した:
3.その後、出芽酵母の約5×105個の細胞を、1μMコレトクロリンB、もしくは1μMアゾキシストロビン、または1μMコレトクロリンと1μMアゾキシストロビンとの組み合わせを含有するYPG寒天プレート上に置いた:
4.プレートを、30℃で3〜5日間増殖させた:
5.その後、阻害剤によって引き起こされる真菌/酵母増殖の阻害の程度を評価した。
本発明者らは、出芽酵母に対して、コレトクロリンBおよびアゾキシストロビンを、個別に(図8aおよびb)、ならびに組み合わせて(図8c)試験した。化合物が別個に使用される際には、真菌の部分的な増殖阻害が観察された。しかしながら、組み合わせで使用される際には、完全な阻害が観察された。したがって、驚くべきことに、本発明者らは、AOX阻害剤および従来の殺真菌薬を含む製剤が、真菌感染症を治療または予防するために有効に使用され得ることを実証した。
Claims (24)
- 抗真菌剤および式Iを有する化合物を含む抗真菌組成物:
R2が、水素またはヒドロキシ基または1〜3個のC原子を有するアルコキシ基であり、
R3が、C1〜C4アルキル基で一置換または多置換されていてもよい、4〜20個のC原子を有する直鎖または分岐のアルキルまたはアルキレンであり、
R4が、水素またはヒドロキシ基または1〜3個のC原子を有するアルコキシ基であり、
R5が、ハロゲン基であり、かつ
R6が、HまたはC1〜C4アルキル基であり、
但し、R2およびR4のうち少なくとも一方が、ヒドロキシ基または1〜3個のC原子を有するアルコキシ基である。 - 前記抗真菌剤が、フェニルアミド殺真菌薬ファミリーの一員、ストロビルリンファミリーの一員、脱メチル化阻害剤、CuPC33、ボスカリド、ジフェンコンコゾール、およびピラクロストロビンからなる抗真菌剤の群より選択される、請求項1に記載の抗真菌組成物。
- 前記ストロビルリンファミリーの一員が、アゾキシストロビンである、請求項2に記載の抗真菌組成物。
- R1が、CHO、CH2OH、CN、CH3、C(O)NH2、C(O)NHCH3、C(O)CH3、CF2CH3、CH2CH3、CH2OAc、COOH、およびCOOCH3から選択される基である、請求項1〜3のいずれか1項に記載の抗真菌組成物。
- R2が、短鎖アルキル基、例えば、メチル基、エチル基またはプロピル基であり、好ましくはR2がヒドロキシル基である、請求項1〜4のいずれか1項に記載の抗真菌組成物。
- R3が、C1〜C4アルキル基で一置換または多置換されていてもよい、6〜15個のC原子、8〜12個のC原子または8〜10個のC原子を有する直鎖または分岐のアルキルまたはアルキレンであり、R3が、少なくとも1つ、好ましくは少なくとも2つのメチル基で置換されている6〜15個のC原子を有する分岐ジエンである、請求項1〜5のいずれか1項に記載の抗真菌組成物。
- R4がメチル基、エチル基またはプロピル基であり、好ましくはR4がヒドロキシル基である、請求項1〜6のいずれか1項に記載の抗真菌組成物。
- R5が塩素基、臭素基、フッ素基またはヨウ素基であり、好ましくはR5が塩素基である、請求項1〜7のいずれかに記載の抗真菌組成物。
- R6がメチル基、エチル基またはプロピル基であり、好ましくはR4がメチル基である、請求項1〜8のいずれかに記載の抗真菌組成物。
- R1が、CHO、CH2OH、CN、CH3、C(O)NH2、C(O)NHCH3、C(O)CH3、CF2CH3、CH2CH3、CH2OAc、COOH、およびCOOCH3から選択され、この際
R2が、ヒドロキシル基であり、
R3が、C1〜C4アルキル基で一置換または多置換されていてもよい、4〜20個のC原子を有する直鎖または分岐のアルキルまたはアルキレンであり、
R4が、ヒドロキシル基であり、
R5が、塩素原子であり、かつ
R6が、HまたはC1〜C4アルキル基である、請求項1〜9のいずれか1項に記載の抗真菌組成物。 - R1が、CHO、CH2OH、CN、CH3、C(O)NH2、C(O)NHCH3、C(O)CH3、CF2CH3、CH2CH3、CH2OAc、COOH、およびCOOCH3から選択され、かつ
R2が、ヒドロキシル基であり、
R3が、C1〜C4アルキル基で一置換または多置換されていてもよい、6〜15個のC原子を有する直鎖または分岐のアルキルまたはアルキレンであり、
R4が、ヒドロキシル基であり、
R5が、塩素原子であり、かつ
R6が、HまたはC1〜C4アルキル基である、請求項1〜10のいずれか1項に記載の抗真菌組成物。 - R1が、CHO、CH2OH、CN、CH3、C(O)NH2、C(O)NHCH3、C(O)CH3、CF2CH3、CH2CH3、CH2OAc、COOH、およびCOOCH3から選択され、かつ
R2が、ヒドロキシル基であり、
R3が、8〜10個のC原子を有するアルキレン鎖であり、かつ少なくとも1つのメチル基、好ましくは少なくとも2つのメチル基で置換されており、
R4が、ヒドロキシル基であり、
R5が、塩素原子であり、かつ
R6が、メチル基である、請求項1〜11のいずれか1項に記載の抗真菌組成物。 - R1が、CHOであり、
R2が、ヒドロキシル基であり、
R3が、8〜10個のC原子を有するアルキレン鎖であり、かつ少なくとも1つのメチル基、好ましくは少なくとも2つのメチル基で置換されており、
R4が、ヒドロキシル基であり、
R5が、塩素原子であり、かつ
R6が、メチル基である、請求項1〜12のいずれか1項に記載の抗真菌組成物。 - 式Iを有する化合物がコレトクロリンBである、請求項1〜13のいずれか1項に記載の抗真菌組成物。
- 請求項1〜14のいずれか1項に記載の抗真菌組成物を含む、農薬組成物。
- 請求項1〜14のいずれか1項に記載の抗真菌組成物の、農薬としての使用。
- 植物の農芸化学的病害または感染症を治療、改善または予防する方法であって、そのような治療を必要とする植物を、農芸化学的に有効な量の抗真菌剤および式Iを有する化合物と接触させることを含む、方法。
- 前記植物を、請求項1〜14のいずれか1項に記載の前記抗真菌組成物と接触させることを含む、請求項17に記載の方法。
- 治療にまたは薬剤として使用される、請求項1〜14のいずれか1項に記載の抗真菌組成物。
- 真菌感染症の治療に使用される、請求項1〜14のいずれか1項に記載の抗真菌組成物。
- 前記病害または感染症が、クララ・フラキシニア、葉枯病菌、立枯病菌、イネ熱病菌、イネいもち病菌、リゾクトニア・ソラニ、ボトリティス・シネレア、フシクラジウム・エフスム(クラドスポリウム・カリイゲナムおよびフシクラドスポリウム・エフスムと同義)、キヤリーヤ・イリノイネンシス、ポドスフェラ・フスカ、ミクロドキウム・ニバーレ、ミクロドキウム・マジャス、コムギふ枯病菌、タペシア・アクホルミス、マイコスファエレラ・フィジエンシス、メタリジウム・アニソプリエ、糸状菌、子嚢菌、アスペルギルス属、ブルメリア属、カンジダ属、クリプトコッカス属、エンセファリトゾーン属、フサリウム属、レプトスフェリア属、マグナポルテ属、フィトフトラ属、プラズモパラ属、ニューモシスチス属、ピリキュラリア属、フィチウム属、プッシニア属、リゾクトニア属、リコフィトン属、ウスチラゴ属、ならびにサッカロミケス菌種からなる群から選択される生物に起因する、請求項16もしくは19〜20のいずれか1項に記載の抗真菌組成物の使用、または請求項17もしくは18に記載の方法。
- 前記病害または感染症が、サッカロミケス菌種またはカンジダ菌種などの酵母に起因する、請求項16もしくは19〜20のいずれか1項に記載の抗真菌組成物の使用、または請求項17もしくは18に記載の方法。
- 請求項1〜14のいずれか1項に記載の組成物および薬学的に許容される賦形剤を含む、抗真菌医薬組成物。
- 請求項23に記載の抗真菌医薬組成物の製造方法であって、治療上有効な量の抗真菌剤および式Iを有する化合物を、薬学的に許容される賦形剤と接触させることを含む、方法。
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PCT/GB2015/050148 WO2015110820A1 (en) | 2014-01-23 | 2015-01-23 | Antifungal Composition |
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JP2008056602A (ja) * | 2006-08-31 | 2008-03-13 | Nihon Green & Garden Corp | 芝病害防除組成物 |
JP2013507372A (ja) * | 2009-10-07 | 2013-03-04 | ダウ アグロサイエンシィズ エルエルシー | 穀類において真菌を制御するための相乗的殺真菌混合物 |
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ES2773624T3 (es) | 2020-07-13 |
CN106413400B (zh) | 2022-03-25 |
PH12016501448B1 (en) | 2016-08-22 |
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