JP5484728B2 - 抗寄生虫治療薬および抗癌治療薬ならびにリジン特異的デメチラーゼ阻害物質として有用なポリアミン類 - Google Patents
抗寄生虫治療薬および抗癌治療薬ならびにリジン特異的デメチラーゼ阻害物質として有用なポリアミン類 Download PDFInfo
- Publication number
- JP5484728B2 JP5484728B2 JP2008526193A JP2008526193A JP5484728B2 JP 5484728 B2 JP5484728 B2 JP 5484728B2 JP 2008526193 A JP2008526193 A JP 2008526193A JP 2008526193 A JP2008526193 A JP 2008526193A JP 5484728 B2 JP5484728 B2 JP 5484728B2
- Authority
- JP
- Japan
- Prior art keywords
- substituted
- alkyl
- unsubstituted
- compound
- formula
- 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 - Fee Related
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/18—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to carbon atoms of six-membered aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/02—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C211/09—Diamines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/16—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of a saturated carbon skeleton containing rings other than six-membered aromatic rings
- C07C211/18—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of a saturated carbon skeleton containing rings other than six-membered aromatic rings containing at least two amino groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/20—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an acyclic unsaturated carbon skeleton
- C07C211/22—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an acyclic unsaturated carbon skeleton containing at least two amino groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/33—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C211/34—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of a saturated carbon skeleton
- C07C211/36—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of a saturated carbon skeleton containing at least two amino groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/43—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C211/44—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to only one six-membered aromatic ring
- C07C211/49—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to only one six-membered aromatic ring having at least two amino groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C215/04—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated
- C07C215/06—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic
- C07C215/14—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic the nitrogen atom of the amino group being further bound to hydrocarbon groups substituted by amino groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/34—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups
- C07C233/35—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/38—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a carbon atom of an acyclic unsaturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C247/00—Compounds containing azido groups
- C07C247/02—Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton
- C07C247/12—Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/04—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/04—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton
- C07C279/12—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by nitrogen atoms not being part of nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/20—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylguanidines
- C07C279/24—Y being a hetero atom
- C07C279/26—X and Y being nitrogen atoms, i.e. biguanides
- C07C279/265—X and Y being nitrogen atoms, i.e. biguanides containing two or more biguanide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/24—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/25—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C381/00—Compounds containing carbon and sulfur and having functional groups not covered by groups C07C301/00 - C07C337/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids R2P(=O)(OH); Thiophosphinic acids, i.e. R2P(=X)(XH) (X = S, Se)
- C07F9/32—Esters thereof
- C07F9/3258—Esters thereof the ester moiety containing a substituent or a structure which is considered as characteristic
- C07F9/3264—Esters with hydroxyalkyl compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/18—Systems containing only non-condensed rings with a ring being at least seven-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/36—Systems containing two condensed rings the rings having more than two atoms in common
- C07C2602/42—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing seven carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
- C07C2603/20—Acenaphthenes; Hydrogenated acenaphthenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/40—Ortho- or ortho- and peri-condensed systems containing four condensed rings
- C07C2603/42—Ortho- or ortho- and peri-condensed systems containing four condensed rings containing only six-membered rings
- C07C2603/50—Pyrenes; Hydrogenated pyrenes
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Tropical Medicine & Parasitology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Pyrrole Compounds (AREA)
Description
本出願は、2005年8月10日に出願された米国仮出願第60/707,420号、の利益を主張する。これらの仮出願の全内容は、参照により本願に組み込まれている。
本発明は、癌および/または寄生虫感染の処置、ならびにリジン特異的デメチラーゼの阻害に有用な、ポリアミン/グアニジンおよびポリアミン/ビグアニド化合物を含むポリアミン化合物に関する。
ポリアミン類は、真核細胞および原核細胞の両方に含まれており、細胞周期および細胞分裂の制御に顕著な関わりがある。ポリアミン類似体などの、ポリアミン生合成を特異的に処置する剤は、癌、寄生虫性疾患、および他の感染症の処置における治療効果が示されている。これらの抗増殖効果は、ポリアミン生合成の阻害、ダウンレギュレーションおよび/またはポリアミン異化のアップレギュレーションがもたらす、天然細胞内ポリアミン類の剤誘導減少の結果であると、ある程度実証されている。
本発明は、ポリアミン、ポリアミン/グアニジン、およびポリアミン/ビグアニド化合物、ならびに癌の処置および予防のためのこれらの化合物の使用を包含する。本発明はまた、リジン特異的デメチラーゼ−1の阻害、およびリジン特異的デメチラーゼ−1に関与する病気の処置のためのこれらの化合物の使用に関する。
E−X−A−NH−B−NH−A−X−E (M)
式中、
それぞれのEは独立して、水素、C1〜C8置換または非置換アルキル、C4〜C15置換または非置換シクロアルキル、C3〜C15置換または非置換分岐アルキル、C6〜C20置換または非置換アリールまたはヘテロアリール、C7〜C24置換または非置換アラルキルまたはヘテロアルキルまたはヘテロアラルキル、C3〜C24置換または非置換ヘテロアリールからなる群から選択され;それぞれのAは独立して、C1〜C8置換または非置換n−アルキルであり;Bは独立して、C1〜C12n−アルキルまたはC3〜C8シクロアルキルから選択され;それぞれのXは、独立して、−NH−、−NH−C(=NH)−NH−、および−NH−C(=NH)−NH−C(=NH)−NH−から選択される;
で表される化合物、および全ての塩、溶媒和物、水和物ならびにこれらの立体異性体を包含する。
別の態様において、少なくとも1つのXは、−NH−C(=NH)−NH−および−NH−CC(=NH)−NH−C(=NH)−NH−から選択される。別の態様において、少なくとも1つのXは、−NH−C(=NH)−NH−である。別の態様において、少なくとも1つのXは、−NH−C(=NH)−NH−C(=NH)−NH−である。別の態様において、それぞれのXは独立して、−NH−C(=NH)−NH−および−NH−C(=NH)−NH−C(=NH)−NH−から選択される。別の態様において、両方のX基は、−NH−C(=NH)−NH−である。別の態様において、両方のX基は、−NH−C(=NH)−NH−C(=NH)−NH−である。別の態様において、1つのXは、−NH−C(=NH)−NH−であり、もう1つのXは、−NH−C(=NH)−NH−C(=NH)−NH−である。
一態様において、R20およびR21の少なくとも1つは水素である。一態様において、R20およびR21の少なくとも1つは、C1〜C8置換または非置換アルキルであり、例えば式(I)〜(VI)に関して上記した、あらゆる置換または非置換アルキル部分などである。一態様において、R20およびR21の少なくとも1つは、C7〜C24置換または非置換アラルキルであり、例えば式(I)〜(VI)に関して上記した、あらゆる置換または非置換アラルキルなどである。
別の態様において、本発明は、式(M)の化合物の1または2以上を治療的に効果的な量で投与することにより、癌を処置する方法を包含する。
別の態様において、本発明は、式(II)の化合物の1または2以上を治療的に効果的な量で投与することにより、癌を処置する方法を包含する。
別の態様において、本発明は、式(IV)の化合物の1または2以上を治療的に効果的な量で投与することにより、癌を処置する方法を包含する。
別の態様において、本発明は、式(VI)の化合物の1または2以上を治療的に効果的な量で投与することにより、癌を処置する方法を包含する。
別の態様において、本発明は、式(VIII)の化合物の1または2以上を治療的に効果的な量で投与することにより、癌を処置する方法を包含する。
別の態様において、本発明は、表Aまたは表Bに記載の化合物の1または2以上を治療的に効果的な量で投与することにより、癌を処置する方法を包含する。
詳細な説明
この開示は、本明細書において記載される化合物の全ての塩を含む。本発明は、本明細書において挙げられた化合物のあらゆる塩の全ての非塩化合物、ならびに本明細書において挙げられた化合物のあらゆる塩の他の塩も含む。一態様において、化合物の塩は、薬学的に許容し得る塩を含む。薬学的に許容し得る塩は、自由化合物の生物活性を保持する塩であり、薬剤または医薬品として、ヒトおよび/または動物に投与することができるものである。
本明細書に記載のあらゆる化合物は、複合の塩および溶媒和物形状で生じてもよく、例えばヒクレート(hyclate)(モノヒドロクロリドヘミエタノラート半水和物)形状である。
本発明において有用な化合物の例は表Aに表現される。化合物は塩、例えば臭化水素酸またはトリフルオロ酢酸塩として表現されているが、表における開示は、当業者に十分理解されるように、当該化合物の非塩、非水和物/非溶媒和物形状だけでなく、表現された化合物の全ての塩、水和物、および溶媒和物、ならびに当該化合物の非塩を包含すると理解される。
対称置換または非対称置換ポリアミン類似体両方を含む、ポリアミン類似化合物の合成に関して、いくつかの合成方法が利用できる。これらの方法のいくつかは、以下の文献に記載されている:Saab et al, J. Med. Chem. 36:2998 (1993);Bellevue et al., Bioorg. Med. Chem. Lett. 6:2765 (1996);Sirisoma et al., Tetrahedron Lett. 39:1489 (1998);Zou et al., Bioorg. Med. Chem. Lett. 11:1613 (2001), and Casero et al., J. Med. Chem. 44:1 (2001)。
ポリアミノビグアニドの合成は、Bi et al., Bioorg. Med. Chem. Lett. 16:3229 (2006)に記載され、スキーム4に概略される。
ヒストン類は、真核細胞に存在し、DNAの補助骨格として働く(時々、DNA糸を補助するタンパク質スプールと比較される)。ヒストン類は、他のタンパク質およびDNAと共に、細胞核のクロマチンを形成する。これらのDNAとの近接接合のため、ヒストン類は遺伝子調節の役割を果たす。ヒストンタンパク質の尾部は、遺伝子発現に影響する共有結合修飾の好発部位である。
いくつかのポリアミン化合物およびポリアミン類似体が、強力な抗癌活性を示した。ポリアミン類およびポリアミン類似体はポリアミン輸送システムを介して細胞内に入り、ポリアミン生合成酵素オルニチンデカルボキシラーゼ(ODC)およびS−アデノシルメチオニン・デカルボキシラーゼ(AdoMet−DC)を下方制御すると考えられている。
96時間選択した化合物にさらした後、H157、H82およびA549細胞におけるMTS用量反応実験を行った。MTSは、細胞における代謝活性を測定する、標準的な比色分析である。MTS実験は、Promega CorporationのCellTiter 96(R) AQUeuos One Solution Cell Proliferation Assayによって行った。簡潔には、細胞を100ul培地/ウェルを含む96ウェル組織培養プレートに3000細胞/ウェルで蒔き、一晩付着させた。
Claims (10)
- 式(I):
nは、1〜12の整数であり;
mおよびpは独立して、1〜5の整数であり;
qは、0または1であり;
それぞれのR1は独立して、C1〜C8置換または非置換アルキル、C4〜C15置換または非置換シクロアルキル、C3〜C15置換または非置換分岐アルキル、C6〜C20置換または非置換アリール、C6〜C20置換または非置換ヘテロアリール、C7〜C24置換または非置換アラルキル、およびC7〜C24置換または非置換ヘテロアラルキルからなる群から選択され;
それぞれのR2は独立して、水素、またはC1〜C8置換または非置換アルキルから選択される、
で表される化合物、またはその塩、溶媒和物、もしくは水和物。 - 式(II):
nは、1〜12の整数であり;
mおよびpは独立して、1〜5の整数であり;
qは、0または1であり;
それぞれのR1は独立して、C1〜C8置換または非置換アルキル、C6〜C20置換または非置換アリール、およびC7〜C24置換または非置換アラルキルからなる群から選択され;
それぞれのR2は独立して、水素、またはC1〜C8置換または非置換アルキルである、
で表される化合物、またはその塩、溶媒和物、もしくは水和物。 - 化合物が
- 請求項1〜3のいずれか一項に記載の化合物および薬学的に許容し得る担体を含む医薬組成物。
- 抗癌剤または抗寄生虫剤としての請求項1〜3のいずれか一項に記載の化合物と、使用説明書を含むキット。
- 請求項1〜3のいずれか一項に記載の化合物を、ヒストンデメチラーゼを少なくとも約50%阻害するのに十分な量で含む、ヒストンデメチラーゼを阻害するための医薬組成物。
- 請求項1〜3のいずれか一項に記載の化合物を治療的に効果的な量で含む、癌を処置するための医薬組成物。
- 請求項1〜3のいずれか一項に記載の化合物を治療的に効果的な量で含む、非制御細胞増殖を処置するための医薬組成物。
- 請求項1〜3のいずれか一項に記載の化合物を治療的に効果的な量で含む、寄生虫感染を処置するための医薬組成物。
- ヒストンデメチラーゼがリジン特異的デメチラーゼ−1である、請求項6に記載の医薬組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US70742005P | 2005-08-10 | 2005-08-10 | |
US60/707,420 | 2005-08-10 | ||
PCT/US2006/031198 WO2007021839A2 (en) | 2005-08-10 | 2006-08-10 | Polyamines useful as anti-parasitic and anti-cancer therapeutics and as lysine-specific demethylase inhibitors |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2009509922A JP2009509922A (ja) | 2009-03-12 |
JP5484728B2 true JP5484728B2 (ja) | 2014-05-07 |
Family
ID=37672417
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008526193A Expired - Fee Related JP5484728B2 (ja) | 2005-08-10 | 2006-08-10 | 抗寄生虫治療薬および抗癌治療薬ならびにリジン特異的デメチラーゼ阻害物質として有用なポリアミン類 |
Country Status (10)
Country | Link |
---|---|
US (2) | US20070208082A1 (ja) |
EP (1) | EP1940773B1 (ja) |
JP (1) | JP5484728B2 (ja) |
KR (1) | KR20080088570A (ja) |
CN (1) | CN101410367A (ja) |
AU (1) | AU2006279943B2 (ja) |
BR (1) | BRPI0614805A2 (ja) |
CA (1) | CA2619005A1 (ja) |
RU (1) | RU2008108632A (ja) |
WO (1) | WO2007021839A2 (ja) |
Families Citing this family (53)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008127734A2 (en) * | 2007-04-13 | 2008-10-23 | The Johns Hopkins University | Lysine-specific demethylase inhibitors |
US8293586B2 (en) * | 2008-09-25 | 2012-10-23 | Infineon Technologies Ag | Method of manufacturing an electronic system |
GB0818907D0 (en) * | 2008-10-15 | 2008-11-19 | Isis Innovation | Histone lysine demethylase inhibitors |
CA2747398C (en) | 2008-12-17 | 2023-06-20 | The Scripps Research Institute | Generation and maintenance of stem cells |
WO2010084160A1 (en) | 2009-01-21 | 2010-07-29 | Oryzon Genomics S.A. | Phenylcyclopropylamine derivatives and their medical use |
JP5685764B2 (ja) * | 2009-04-10 | 2015-03-18 | 国立大学法人 熊本大学 | ミトコンドリア機能向上剤 |
EP2258865A1 (en) * | 2009-06-05 | 2010-12-08 | Universitätsklinikum Freiburg | Lysine-specific demethylase 1 (LSD1) is a biomarker for breast cancer |
US9708255B2 (en) | 2009-08-18 | 2017-07-18 | Robert A. Casero | (bis)urea and (bis)thiourea compounds as epigenic modulators of lysine-specific demethylase 1 and methods of treating disorders |
MX338041B (es) | 2009-09-25 | 2016-03-30 | Oryzon Genomics Sa | Inhibidores de demetilasa-1 especificos de lisina y su uso. |
EP2486002B1 (en) | 2009-10-09 | 2019-03-27 | Oryzon Genomics, S.A. | Substituted heteroaryl- and aryl- cyclopropylamine acetamides and their use |
US9186337B2 (en) | 2010-02-24 | 2015-11-17 | Oryzon Genomics S.A. | Lysine demethylase inhibitors for diseases and disorders associated with Hepadnaviridae |
US9616058B2 (en) | 2010-02-24 | 2017-04-11 | Oryzon Genomics, S.A. | Potent selective LSD1 inhibitors and dual LSD1/MAO-B inhibitors for antiviral use |
US20130197088A1 (en) * | 2010-03-12 | 2013-08-01 | Robert A. Casero, JR. | Compositions and Methods for Combinations of Oligoamines with 2-Difluoromethylornithine (DFMO) |
KR101794020B1 (ko) | 2010-04-19 | 2017-11-06 | 오리존 지노믹스 에스.에이. | 라이신 특이적 디메틸라아제-1 억제제 및 이의 용도 |
US9181198B2 (en) | 2010-07-29 | 2015-11-10 | Oryzon Genomics S.A. | Arylcyclopropylamine based demethylase inhibitors of LSD1 and their medical use |
WO2012013727A1 (en) | 2010-07-29 | 2012-02-02 | Oryzon Genomics S.A. | Cyclopropylamine derivatives useful as lsd1 inhibitors |
WO2012045883A1 (en) | 2010-10-08 | 2012-04-12 | Oryzon Genomics S.A. | Cyclopropylamine inhibitors of oxidases |
WO2012071469A2 (en) * | 2010-11-23 | 2012-05-31 | Nevada Cancer Institute | Histone demethylase inhibitors and uses thereof for treatment o f cancer |
WO2012072713A2 (en) | 2010-11-30 | 2012-06-07 | Oryzon Genomics, S.A. | Lysine demethylase inhibitors for diseases and disorders associated with flaviviridae |
EP2712315B1 (en) | 2011-02-08 | 2021-11-24 | Oryzon Genomics, S.A. | Lysine demethylase inhibitors for myeloproliferative disorders |
US20140163041A1 (en) | 2011-02-08 | 2014-06-12 | Oryzon Genomics S.A. | Lysine demethylase inhibitors for myeloproliferative or lymphoproliferative diseases or disorders |
WO2012156537A2 (en) | 2011-05-19 | 2012-11-22 | Oryzon Genomics, S.A. | Lysine demethylase inhibitors for thrombosis and cardiovascular diseases |
WO2012156531A2 (en) | 2011-05-19 | 2012-11-22 | Oryzon Genomics, S.A. | Lysine demethylase inhibitors for inflammatory diseases or conditions |
US9289415B2 (en) | 2011-09-01 | 2016-03-22 | The Brigham And Women's Hospital, Inc. | Treatment of cancer |
CN107266345B (zh) | 2011-10-20 | 2021-08-17 | 奥瑞泽恩基因组学股份有限公司 | 作为lsd1抑制剂的(杂)芳基环丙胺化合物 |
RS58475B1 (sr) | 2011-10-20 | 2019-04-30 | Oryzon Genomics Sa | Jedinjenja (hetero)aril ciklopropilamina kao lsd1 inhibitori |
US9439433B2 (en) | 2013-05-22 | 2016-09-13 | Curza Global, Llc | Compositions and methods comprising a biocidal polyamine |
US9034927B2 (en) | 2013-05-22 | 2015-05-19 | Curza Global, Llc | Methods of use for compositions comprising a biocidal polyamine |
WO2014190096A1 (en) * | 2013-05-22 | 2014-11-27 | Curza Global, Llc | Compositions and methods comprising a polyamine |
AU2014302038B2 (en) | 2013-06-25 | 2019-11-14 | Epiaxis Therapeutics Pty Ltd | Methods and compositions for modulating cancer stem cells |
CA2958704A1 (en) | 2014-08-25 | 2016-03-03 | University Of Canberra | Compositions for modulating cancer stem cells and uses therefor |
EP3090998A1 (en) | 2015-05-06 | 2016-11-09 | F. Hoffmann-La Roche AG | Solid forms |
US20180284095A1 (en) | 2015-06-12 | 2018-10-04 | Oryzon Genomics, S.A. | Biomarkers associated with lsd1 inhibitors and uses thereof |
WO2017013061A1 (en) | 2015-07-17 | 2017-01-26 | Oryzon Genomics, S.A. | Biomarkers associated with lsd1 inhibitors and uses thereof |
EP3397756B1 (en) | 2015-12-30 | 2023-03-08 | Novartis AG | Immune effector cell therapies with enhanced efficacy |
KR102646126B1 (ko) | 2016-03-15 | 2024-03-11 | 오리존 지노믹스 에스.에이. | 혈액 악성 종양의 치료를 위한 lsd1 억제제의 조합물 |
KR20230042756A (ko) | 2016-03-15 | 2023-03-29 | 오리존 지노믹스 에스.에이. | 고형 종양의 치료에 사용하기 위한 lsd1 억제제의 조합물 |
JP2019512546A (ja) | 2016-03-16 | 2019-05-16 | オリゾン・ゲノミクス・ソシエダッド・アノニマ | Kdm1a標的会合を決定するための方法、およびそれに有用な化学プローブ |
SG11201710199PA (en) | 2016-06-10 | 2018-05-30 | Oryzon Genomics Sa | Methods of treating multiple sclerosis |
EP3535420A1 (en) | 2016-11-03 | 2019-09-11 | Oryzon Genomics, S.A. | Biomarkers for determining responsiveness to lsd1 inhibitors |
KR20190093621A (ko) * | 2016-12-08 | 2019-08-09 | 란케나우 인스티튜트 포 메디칼 리서치 | 면역조절 화합물 |
WO2018107173A1 (en) * | 2016-12-09 | 2018-06-14 | Vanderbilt University | Glutamine transport inhibitors and methods for treating cancer |
CN110785082B (zh) | 2017-04-05 | 2021-12-28 | 库扎环球有限责任公司 | 包含三芳基聚胺的组合物和方法 |
SG11202000077RA (en) | 2017-08-03 | 2020-02-27 | Oryzon Genomics Sa | Methods of treating behavior alterations |
WO2019068326A1 (en) | 2017-10-05 | 2019-04-11 | Université D'aix-Marseille | INHIBITORS OF LSD1 FOR THE TREATMENT AND PREVENTION OF CARDIOMYOPATHIES |
JP7164114B2 (ja) * | 2018-01-19 | 2022-11-01 | 学校法人 名古屋電気学園 | バナジウム錯体及びそれを用いた窒素固定方法 |
JP6708764B1 (ja) * | 2019-01-28 | 2020-06-10 | 久保田 徹 | 機能水 |
WO2020188089A1 (en) | 2019-03-20 | 2020-09-24 | Oryzon Genomics, S.A. | Methods of treating attention deficit hyperactivity disorder using kdm1a inhibitors such as the compound vafidemstat |
BR112021016064A2 (pt) | 2019-03-20 | 2021-10-05 | Oryzon Genomics, S.A. | Métodos de tratamento do transtorno de personalidade borderline |
CN111840298A (zh) * | 2019-04-26 | 2020-10-30 | 湖北工业大学 | 小分子抑制剂在制备抑制鸟氨酸脱羧酶与鸟氨酸脱羧酶抗酶1的相互作用的制药用途 |
EP3994280A1 (en) | 2019-07-05 | 2022-05-11 | Oryzon Genomics, S.A. | Biomarkers and methods for personalized treatment of small cell lung cancer using kdm1a inhibitors |
EP3964204A1 (en) | 2020-09-08 | 2022-03-09 | Université d'Aix-Marseille | Lsd1 inhibitors for use in the treatment and prevention of fibrosis of tissues |
EP4169902A1 (en) * | 2021-10-25 | 2023-04-26 | Consejo Superior de Investigaciones Científicas (CSIC) | Spermine derivatives as heparin antidotes |
Family Cites Families (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1114155A (en) * | 1964-08-24 | 1968-05-15 | Evans Medical Ltd | Guanidino derivatives |
GB1434040A (en) * | 1973-08-06 | 1976-04-28 | Ici Ltd | Process for combating fungi and bacteria |
US4252951A (en) * | 1979-10-09 | 1981-02-24 | Eli Lilly And Company | Isolation of syn-7-(2-amino-4-thiazolyl)-(methoxyimino)acetamido-3-acetoxymethyl-3-cephem-4-carboxylic acid |
JPS57501081A (ja) * | 1980-06-24 | 1982-06-24 | ||
DE3531356A1 (de) * | 1985-09-03 | 1987-03-12 | Hoechst Ag | Mikrobiozide mittel auf basis von alkyl-di-guanidiniumsalzen |
US5091576A (en) * | 1986-12-02 | 1992-02-25 | University Of Florida | Anti-neoplastic, anti-viral or anti-retroviral spermine derivatives |
US5342945A (en) * | 1986-12-02 | 1994-08-30 | University Of Florida Research Foundation, Inc. | Anti-neoplastic, anti-viral or anti-retroviral spermine derivatives |
NZ223340A (en) * | 1987-02-03 | 1991-03-26 | Merrell Dow Pharma | Polyamine derivatives and pharmaceutical compositions |
US5753714A (en) * | 1987-02-03 | 1998-05-19 | Merrell Pharmaceuticals Inc. | Polyamine derivatives |
ZA887410B (en) * | 1987-10-08 | 1989-06-28 | Merrell Dow Pharma | Polyamine derivatives as antineoplastic agents |
US5541230A (en) * | 1993-11-05 | 1996-07-30 | Us Health | Therapeutic polyamines |
ES2119371T3 (es) * | 1993-12-27 | 1998-10-01 | Novartis Ag | Aminocompuestos insaturados para usar como un agente anticancerigeno y antiprotozoico. |
DE69711413T2 (de) | 1996-10-18 | 2002-07-18 | Wisconsin Alumni Res Found | In ihrer konformation eingeschränkte polyamine und ihre verwendung als antineoplastische mittel |
FR2763943B1 (fr) * | 1997-05-28 | 1999-07-09 | Rhone Poulenc Rorer Sa | Composes, leur preparation et leur utilisation pour le transfert d'acides nucleiques dans les cellules |
US5889061A (en) * | 1997-10-15 | 1999-03-30 | Wisconsin Alumni Research Foundation | Conformationally restricted polyamines |
JP3747355B2 (ja) * | 1998-12-21 | 2006-02-22 | 独立行政法人理化学研究所 | 鎖状ポリアミン系化合物及びポリアミン系抗ガン剤 |
US6794545B1 (en) | 1999-04-30 | 2004-09-21 | Slil Biomedical Corporation | Conformationally restricted polyamine analogs as disease therapies |
EP1305299A1 (en) | 2000-08-02 | 2003-05-02 | SLIL Biomedical Corporation | Cyclic polyamine compounds for cancer therapy |
AU2002235126A1 (en) * | 2000-11-08 | 2002-05-21 | Slil Biomedical Corporation | Novel polyamine analog-amino acid conjugates useful as anticancer agents |
WO2002100884A2 (en) * | 2001-06-13 | 2002-12-19 | The Johns Hopkins University School Of Medicine | Cloned mammalian polyamine oxidase |
MXPA04005509A (es) | 2001-12-07 | 2004-12-06 | Slil Biomedical Corp | Poliaminas sustituidas con cicloalquilo para terapia de cancer y metodos de sintesis de las mismas. |
KR20040091014A (ko) * | 2002-02-07 | 2004-10-27 | 위스콘신 얼럼나이 리서어치 화운데이션 | 항암 요법과 병행해서 사용하기 위한 폴리아민 화합물 및조성물 |
US7144920B2 (en) * | 2002-09-23 | 2006-12-05 | Mediquest Therapeutics, Inc. | Polyamine analogs that activate antizyme frameshifting |
US7001925B1 (en) * | 2002-09-27 | 2006-02-21 | University Of Central Florida Research Foundation, Inc. | Compounds and method for enhancing the efficacy of anti-cancer drugs |
CA2591717A1 (en) | 2004-12-16 | 2006-07-06 | President And Fellows Of Harvard College | Histone demethylation mediated by the nuclear amine oxidase homolog lsd1 |
-
2006
- 2006-08-10 AU AU2006279943A patent/AU2006279943B2/en not_active Ceased
- 2006-08-10 WO PCT/US2006/031198 patent/WO2007021839A2/en active Application Filing
- 2006-08-10 BR BRPI0614805-0A patent/BRPI0614805A2/pt not_active IP Right Cessation
- 2006-08-10 CN CNA2006800376691A patent/CN101410367A/zh active Pending
- 2006-08-10 KR KR1020087005476A patent/KR20080088570A/ko not_active Application Discontinuation
- 2006-08-10 US US11/463,840 patent/US20070208082A1/en not_active Abandoned
- 2006-08-10 CA CA002619005A patent/CA2619005A1/en not_active Abandoned
- 2006-08-10 EP EP06801144.4A patent/EP1940773B1/en not_active Not-in-force
- 2006-08-10 RU RU2008108632/04A patent/RU2008108632A/ru not_active Application Discontinuation
- 2006-08-10 JP JP2008526193A patent/JP5484728B2/ja not_active Expired - Fee Related
-
2010
- 2010-04-20 US US12/763,722 patent/US8148577B2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
AU2006279943B2 (en) | 2012-02-16 |
WO2007021839A3 (en) | 2007-06-14 |
EP1940773B1 (en) | 2015-03-18 |
US8148577B2 (en) | 2012-04-03 |
RU2008108632A (ru) | 2009-09-20 |
US20100273745A1 (en) | 2010-10-28 |
CN101410367A (zh) | 2009-04-15 |
EP1940773A2 (en) | 2008-07-09 |
JP2009509922A (ja) | 2009-03-12 |
BRPI0614805A2 (pt) | 2011-04-12 |
WO2007021839A2 (en) | 2007-02-22 |
KR20080088570A (ko) | 2008-10-02 |
US20070208082A1 (en) | 2007-09-06 |
AU2006279943A1 (en) | 2007-02-22 |
CA2619005A1 (en) | 2007-02-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5484728B2 (ja) | 抗寄生虫治療薬および抗癌治療薬ならびにリジン特異的デメチラーゼ阻害物質として有用なポリアミン類 | |
US20110092601A1 (en) | Lysine-specific demethylase inhibitors | |
US20130197088A1 (en) | Compositions and Methods for Combinations of Oligoamines with 2-Difluoromethylornithine (DFMO) | |
US5169868A (en) | Aliphatic propargylamines as specific mao-b inhibitors | |
US8524717B2 (en) | Oxidase inhibitors and their use | |
Lakanen et al. | . alpha.-Methyl polyamines: metabolically stable spermidine and spermine mimics capable of supporting growth in cells depleted of polyamines | |
PL194784B1 (pl) | Nowe związki amidynowe, sposób ich wytwarzania, preparat farmaceutyczny zawierający je i zastosowanie tych związków jako inhibitory syntazy tlenku azotu | |
US5344846A (en) | Compositions and methods for inhibiting deoxyhypusine synthase and the growth of cells | |
JP2005511734A (ja) | 癌治療用のシクロアルキル置換ポリアミンおよびそれらの合成方法 | |
DK166080B (da) | Analogifremgangsmaade til fremstilling af et n-oe4-(3-aminopropyl)aminobutylaa-2-(omega-guanidino-fedtsyreamido)-2-substitueret ethanamid eller et salt deraf | |
AU2020394767B2 (en) | Spiro compound serving as ERK inhibitor, and application thereof | |
JPS6284052A (ja) | 〔(2,3,9,9a‐テトラヒドロ―3‐オキソ‐9a‐置換‐1H‐フルオレン―7‐イル)オキシ〕エタンイミドアミド類、〔(2,3,9,9a‐テトラヒドロ‐3‐オキソ‐9a‐置換‐1H‐フルオレン‐7‐イル)オキシ〕エタンイミド酸ヒドラジド類その誘導体および塩 | |
EP0186680A1 (en) | PHENYLISOPROPYLAMINE COMBINATION AND THE PRODUCTION THEREOF. | |
HUT74005A (en) | Polyamine derivatives as radioprotective agents and pharmaceutical compositions containing them | |
JP2722255B2 (ja) | N―2,3―ブタジエニルトリー及びテトラアミノアルカン誘導体類 | |
US3992446A (en) | Substituted aminochlorobenzylamino guanidine compounds | |
MX2008002036A (en) | Polyamines useful as anti-parasitic and anti-cancer therapeutics and as lysine-specific demethylase inhibitors | |
CA1204775A (en) | Decarboxylase-inhibiting fluorinated alkane diamine derivatives | |
EP0072760B1 (en) | Fluorinated diamino-heptene and -heptyne derivatives | |
EP0072762B1 (en) | Fluorinated diaminoalkene derivatives | |
US4935443A (en) | N-substituted-3-nitro-4-(ureidooxymethyl)-benzenesulfonamides as radiation enhancers | |
WO2022187403A1 (en) | Thyroid hormone receptor beta agonist compounds | |
KR20230118883A (ko) | Enpp1 억제제로서의 이미다졸 화합물 | |
GB2104059A (en) | Acetylenic diaminobutane derivatives | |
GB2104074A (en) | Fluorinated diaminohexane derivatives |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20090810 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20120424 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120515 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120814 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120821 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120907 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120914 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20121015 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20121022 |
|
A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121115 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130625 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130924 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20131001 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20131025 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20131101 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20131125 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20131202 |
|
A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20131225 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20140128 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140219 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5484728 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
LAPS | Cancellation because of no payment of annual fees |