2067-58-5

Usage

InChI:InChI=1/C10H14Cl2N2/c11-5-7-14(8-6-12)10-3-1-9(13)2-4-10/h1-4H,5-8,13H2

Upstream product

• 25843-64-5 1-Methyl-2--phenyliminomethyl>chinoliniumchlorid (IMET 3106) 
• 55743-71-0 bis(2-chloroethyl)(4-nitrophenyl)amine 
• 100-00-5 4-chlorobenzonitrile 
• 18226-17-0 N,N-bis(2-hydroxyethyl)-4-nitroaniline 
• 1215-16-3 N,N-bis(2-chloroethyl)-N'-acetyl-1,4-phenylenediamine 
• 120-07-0 2,2'-(phenylimino)bis[ethanol] 
• 122-80-5 N-acetyl-p-phenylenediamine 
• 3069-91-8 4--acetanilid 
• 100-01-6 4-nitro-aniline 
• 350-46-9 4-Fluoronitrobenzene 
• 23721-18-8 N,N-bis<2-<(methylsulfonyl)oxy>ethyl>-4-nitroaniline 

Downstream Products

• 1448-92-6 N-(4--phenyl)-carbaminsaeure-ethylester 
• 119210-39-8 4,4'-Bis--bernsteinsaeure-dianilid 
• 94204-78-1 Malonsaeure-<4-(N,N-bis-(2-chlor-aethyl)-amino)-anilid>-monoaethylester 
• 17273-11-9 N-<4-(N,N-Bis-(2-chloraethyl)-amino)-phenyl>-N'-<4-(methoxycarbonyl)-phenyl>-harnstoff 
• 17273-10-8 N-(4--phenyl)-N'-(ethoxycarbonyl-ethyl)-harnstoff 
• 82484-59-1 4-bis-(β-chloroethyl)aminophenyl isocyanate 
• 68427-04-3 (S)-2-[({4-[Bis-(2-chloro-ethyl)-amino]-phenylcarbamoyl}-methyl)-carbamoyl]-pyrrolidine-1-carboxylic acid benzyl ester 
• 180839-02-5 di-tert-butyl N-<(4-<amino>phenyl)carbamoyloxy>methyl>phenoxy)carbonyl>-L-glutamate 
• 180839-04-7 diprop-2-enyl N-<(4-<amino>phenyl)carbamoyloxy>methyl>phenoxy)carbonyl>-L-glutamate 
• 1446421-19-7 N-(4-(3-(4-(bis(2-chloroethyl)amino)phenyl)ureido)phenyl)-2-(dimethylamino)acetamide 
• 1446421-16-4 N-(4-(3-(4-(bis(2-chloroethyl)amino)phenyl)ureido)phenyl)-3-(piperidin-1-yl)propanamide 
• 1446421-17-5 N-(4-(3-(4-(bis(2-chloroethyl)amino)phenyl)ureido)phenyl)-3-morpholinopropanamide 
• 1446421-18-6 3-([1,4'-bipiperidin]-1'-yl)-N-(4-(3-(4-(bis(2-chloroethyl)amino)phenyl)ureido)phenyl)propanamide 
• 1446420-94-5 N-(3-(3-(4-(bis(2-chloroethyl)amino)phenyl)ureido)phenyl)-2-(dimethylamino)acetamide 

Relevant academic research and scientific papers

Hypoxia-activatable nano-prodrug for fluorescently tracking drug release in mice

Chemotherapy is one of the commonly used methods to treat various types of cancers in clinic by virtue of its high efficiency and universality. However, strong side effects and low concentration of conventional drugs at the tumor site have always been important factors that plague the chemotherapy effects of patients, further precluding their practical applications. Thereof, to solve the above dilemma, by integration of anticancer drug (nitrogen mustard, NM) into an NIR fluorophore (a dicyanoisophorone derivative), an intelligent prodrug NIR-NM was developed via molecular engineering strategy. Prodrug NIR-NM stimulated in hypoxia condition exhibits significantly higher toxicity to cancer cells than normal cells, essentially reducing the collateral damage to healthy cells and tissues of nitrogen mustard. More importantly, the nanoparticle prodrug FA-lip@NIR-NM showed the advantages of the high accumulation of drug at tumor site and long-circulation capacity in vivo, which endowed it the ability to track the release of the active chemotherapeutic drug and further treat solid tumors.[Figure not available: see fulltext.].

N nitrogen mustard derivatives, two N - (2 - chloroethyl) - 1, 4 - phenylenediamine - N' - sixteen-acyl and its preparation method

The invention discloses a structural formula of a nitrogen mustard derivative N,N-di(2-chloroethyl)-N'-hexadecanoyl-1,4-phenylenediamine, and a preparation method thereof. The preparation method comprises the following steps: preparing N,N-di(2-chloroethyl)-1,4-phenylenediamine; putting the reaction raw materials comprising the N,N-di(2-chloroethyl)-1,4-phenylenediamine, dichloromethane and triethylamine into a reactor, cooling in ice-water bath, stirring, dropwise adding a mixed solution of hexadecanoyl chloride and dichloromethane into the reactor, removing the ice-water bath after addition, conducting reaction at room temperature for 12 to 14 hours, sequentially performing washing, drying and normal-pressure distillation on the reaction liquid after the reaction is conducted completely, and purifying the distilled filter cake to obtain the product. The arylamine nitrogen mustard derivative provided by the invention can effectively reduce the toxic and side effects of nitrogen mustard on the premise of enhancing the treatment index of the nitrogen mustard, and has sterilization and inflammation-diminishing curative effects to reduce the risk of complication caused by the fact that the immunity is reduced after a patient is subjected to chemical therapy.

Hydrogen peroxide-responsive nitrogen mustard anti-tumor pro-drug and preparation method thereof

The invention discloses a hydrogen peroxide-responsive nitrogen mustard anti-tumor pro-drug and a preparation method thereof, and belongs to the field of pharmaceutical chemistry. The compound contains an alpha-ketoamide structure and a nitrogen mustard structure, can rapidly respond to H2O2, can be used as the nitrogen mustard anti-tumor pro-drug, has good response effect to H2O2, has high cell selectivity and small toxic and side effects, provides an effective, safe and highly selective anti-tumor drug, enriches the types of nitrogen mustard anti-tumor drugs, and has a good market prospect.

Nitrogen mustard derivative N,N-di(2-chloroethyl)-N'-myristoyl-1,4-phenylenediamine and preparation method thereof

The invention particularly discloses a structural formula of a nitrogen mustard derivative N,N-di(2-chloroethyl)-N'-myristoyl-1,4-phenylenediamine, and a preparation method thereof. The preparation method comprises the following steps: preparing N,N-di(2-chloroethyl)-1,4-phenylenediamine; putting the N,N-di(2-chloroethyl)-1,4-phenylenediamine, dichloromethane and triethylamine into a reactor, cooling in ice-water bath, stirring, dropwise adding a mixed solution of myristyl chloride and dichloromethane into the reactor, removing the ice-water bath after addition, reacting at room temperature for 10 to 14 hours, washing the reaction liquid after the reaction is conducted completely, drying with anhydrous cupric sulfate, performing normal-pressure distillation, and purifying the distilled filter cake to obtain the product. The nitrogen mustard derivative provided by the invention can effectively reduce the toxic and side effects of nitrogen mustard on the premise of enhancing the treatment index of the nitrogen mustard, and has sterilization and inflammation-diminishing curative effects to reduce the risk of complication caused by the fact that the immunity is reduced after a patient is subjected to chemical therapy.

Aryl nitrogen mustard derivative N,N-di(2-chloroethyl)-N'-propionyl-1,4-phenylenediamine and preparation method thereof

The invention particularly discloses a structural formula and preparation method of an aryl nitrogen mustard derivative N,N-di(2-chloroethyl)-N'-propionyl-1,4-phenylenediamine. The method comprises the following steps: preparing N,N-di(2-chloroethyl)-1,4-phenylenediamine; adding the N,N-di(2-chloroethyl)-1,4-phenylenediamine, dichloromethane and triethylamine into a reactor, cooling in an ice water bath, stirring, and dropwisely adding a propionyl chloride-dichloromethane mixed solution into the reactor; after finishing the dropwise addition, removing the ice water bath, and reacting at room temperature for 4-14 hours; and after the reaction finishes, washing the reaction solution, drying with anhydrous cupric sulfate, carrying out atmospheric distillation, and purifying the filter cake. The aryl nitrogen mustard derivative can effectively lower the toxic and side effects of nitrogen mustards on the premise of enhancing the therapeutic index of the nitrogen mustards, and has the curative effects of killing germs and diminishing inflammation, thereby lowering the risk of complications caused by decrease in immunity of the patient after chemotherapy.

Nitrogen mustard derivative N,N-di(2-chloroethyl)-N'-benzoyl-1,4-phenylenediamine and preparation method thereof

The invention particularly discloses a structural formula of a nitrogen mustard derivative N,N-di(2-chloroethyl)-N'-benzoyl-1,4-phenylenediamine, and a preparation method thereof. The preparation method comprises the following steps: preparing N,N-di(2-chloroethyl)-1,4-phenylenediamine; putting the N,N-di(2-chloroethyl)-1,4-phenylenediamine, dichloromethane and triethylamine into a reactor, cooling in ice-water bath, stirring, dropwise adding a mixed solution of benzoyl chloride and dichloromethane into the reactor, removing the ice-water bath after addition, conducting reaction at room temperature for 8 to 14 hours, sequentially performing washing, drying and normal-pressure distillation on the reaction liquid after the reaction is conducted completely, and purifying the distilled filter cake to obtain the product. The arylamine nitrogen mustard derivative provided by the invention can effectively reduce the toxic and side effects of nitrogen mustard on the premise of enhancing the treatment index of the nitrogen mustard, and has sterilization and inflammation-diminishing curative effects to reduce the risk of complication caused by the fact that the immunity is reduced after a patient is subjected to chemical therapy.

Rational design, synthesis and preliminary antitumor activity evaluation of a chlorambucil derivative with potent DNA/HDAC dual-targeting inhibitory activity

Histone deacetylases (HDACs) play a pivotal role not only in gene expression but also in DNA repair. Herein, we report the successful design, synthesis and evaluation of a chlorambucil derivative named vorambucil with a hydroxamic acid tail as a DNA/HDAC dual-targeting inhibitor. Vorambucil obtained both potent DNA and HDACs inhibitory activities. Molecular docking results supported the initial pharmacophoric hypothesis and rationalized the potent inhibitory activity of vorambucil against HDAC1, HDAC2 and HDAC6. Vorambucil showed potent antiproliferative activity against all the test four cancer cell lines with IC50 values of as low as 3.2–6.2 μM and exhibited 5.0–18.3-fold enhanced antiproliferative activity than chlorambucil. Vorambucil also significantly inhibits colony formation of A375 cancer cells. Further investigation showed that vorambucil remarkably induced apoptosis and arrested the cell cycle of A375 cells at G2/M phase. Vorambucil could be a promising candidate and a useful tool to elucidate the role of those DNA/HDAC dual-targeting inhibitors for cancer therapy.

Nitrogen mustard compounds containing hydroxamic acid groups as well as preparation method and application of nitrogen mustard compounds

The invention discloses nitrogen mustard compounds containing hydroxamic acid groups as well as a preparation method and an application of the nitrogen mustard compounds and relates to the field of medicinal chemistry. The compounds have the capability of inhibiting cancer cell proliferation, achieve the purpose of treating cancer and particularly have excellent cancer cell proliferation inhibition activity for inhibiting human cutaneous melanoma A375, human cervical carcinoma cells HeLa, human liver cancer cells HepG2, human lung cancer cells A549 and human colon cancer cells HCT116. The compounds have the structure shown in a general formula I, wherein X1, X2, X3, X4 and Z are defined in the specification.

Pyrazolo [1, 5 - a] pyrimidine nitrogen mustard derivative and its preparation method and tumor therapeutic use

The invention relates to pyrazolo[1,5-alpha] pyrimidine nitrogen mustard derivatives or medical salts thereof, as well as application of the pyrazolo[1,5-alpha] pyrimidine nitrogen mustard derivatives or the medical salts thereof. The pyrazolo[1,5-alpha] pyrimidine nitrogen mustard derivatives and the medical salts thereof have the structure shown as the formula I. Pharmacological experiments show that the pyrazolo[1,5-alpha] pyrimidine nitrogen mustard derivatives and the medical salts thereof have inhibiting effects on the proliferation of various tumor cells. Moreover, the pyrazolo[1,5-alpha] pyrimidine nitrogen mustard derivatives are small in toxicity, have the advantages of selectivity on tumor cells, and are dual-functional anti-tumor drugs. Meanwhile, the pyrazolo[1,5-alpha] pyrimidine nitrogen mustard derivatives are easy to synthesize, and the overall yields are high. All the advantages show that the pyrazolo[1,5-alpha] pyrimidine nitrogen mustard derivatives have great potential of being anti-tumor drugs.

Arylamine nitrogen mustard derivative N,N-bis(2-chloroethyl)-N'-acetyl-1,4-phenylenediamine and preparation method thereof

The invention specifically discloses a structural formula of an arylamine nitrogen mustard derivative N,N-bis(2-chloroethyl)-N'-acetyl-1,4-phenylenediamine and a preparation method of the derivative. The method comprises the following steps: preparing N,N-bis(2-chloroethyl)-1,4-phenylenediamine; filling a reactor with N,N-bis(2-chloroethyl)-1,4-phenylenediamine, dichloromethane and triethylamine, cooling in an ice-water bath, stirring, dropwise adding a mixed solution of acetyl chloride and dichloromethane into the reactor, removing the ice-water bath after dropwise adding, reacting at the room temperature for 2-14 hours, washing, drying and distilling after the reaction is completed, purifying the distilled filter cake, thereby obtaining the product. The arylamine nitrogen mustard derivative disclosed by the invention can effectively reduce the toxic or side effects of nitrogen mustard on the premise of enhancing the therapeutic index of the nitrogen mustard and has the curative effects of sterilizing and diminishing inflammation so as to reduce the risk of causing complications due to decrease in immunity after chemotherapy of a patient.