Towards an efficient prodrug of the alkylating metabolite monomethyltriazene: synthesis and stability of N-acylamino acid derivatives of triazenes.

نویسندگان

  • Maria de Jesus Perry
  • Emília Carvalho
  • Eduarda Rosa
  • Jim Iley
چکیده

A series of 3-[alpha-(acylamino)acyl]-1-aryl-3-methyltriazenes 6a-l, potential cytotoxic triazene prodrugs, were synthesised by coupling 1-aryl-3-methyltriazenes to N-acylamino acids. Their hydrolysis was studied in isotonic pH 7.4 phosphate buffer and in human plasma, while hydrolysis of the derivative 6a was studied in more depth across a range of pH values. Prodrugs 6a-l hydrolyse by cleavage of the triazene acyl group to afford the corresponding monomethyltriazenes. Studies in human plasma demonstrate that acylation of the alpha-amino group of the amino acid carrier is an effective means of reducing the chemical reactivity of the alpha-aminoacyl derivatives while retaining a rapid rate of enzymatic hydrolysis. These derivatives displayed logP values that suggest they should be well absorbed through biological membranes.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

An Efficient Green Approach for the Synthesis of Fluoroquinolones Using Nano Zirconia Sulfuric Acid as Highly Efficient Recyclable Catalyst in two Forms of Water

Various antibacterial fluoroquinolone compounds were prepared by the direct amination of 7-halo-6- fluoroquinolone-3-carboxylic acids with a variety of piperazine derivatives and (4aR,7aR)-octahydro-1H-pyrrolo[3,4-b] pyridine using Zirconia Sulfuric Acid (ZrSA) nanoparticle, as a catalyst in the presence of ordinary or magnetized water upon reflux condition. The results showed that ZrSA exh...

متن کامل

Highly efficient one-pot four-component synthesis of polyhydroquinoline derivatives catalyzed by stannous chloride under solvent-free conditions

A rapid and efficient one-pot, four-component protocol towards the synthesis of polyhydroquinoline derivatives has been developed. The condensation of aldehyde, dimedone, ethyl acetoacetate and ammonium acetate in presence of stannous chloride was carried out under solvent free condition to synthesize a variety of polyhydroquinoline derivatives in good to excellent yields. Stannous chloride was...

متن کامل

Highly efficient one-pot four-component synthesis of polyhydroquinoline derivatives catalyzed by stannous chloride under solvent-free conditions

A rapid and efficient one-pot, four-component protocol towards the synthesis of polyhydroquinoline derivatives has been developed. The condensation of aldehyde, dimedone, ethyl acetoacetate and ammonium acetate in presence of stannous chloride was carried out under solvent free condition to synthesize a variety of polyhydroquinoline derivatives in good to excellent yields. Stannous chloride was...

متن کامل

Silica-bonded n-propyldiethylenetriamine sulfamic acid as a recyclable solid acid catalyst for the synthesis of coumarin and biscoumarin derivatives

Silica-bonded n-propyldiethylenetriamine sulfamic acid (SBPDSA) was found as an efficient solid acid for the synthesis of coumarins. Coumarin derivatives were obtained via the Pechmann condensation reaction of phenols and β-keto-esters at 80 oC under solvent-free conditions. Also, biscoumarins were obtained via the condensation of aldehydes and 4-hydroxycoumarin in water at reflux conditions. T...

متن کامل

Nano Al2O3: An efficient catalyst for the multi-component synthesis of Pyrano [2, 3-d] Pyrimidinone derivatives

Pyrano [2,3-d] pyrimidinone derivatives have received considerable interest from the pharmaceutical industry due to their wide range of interesting biological and therapeutic properties. Nano Al2O3 was found to be a highly efficient solid acid catalyst for the preparation of pyrano [2,3-d] pyrimidinone derivatives from the reaction of barbituric acid, aryl aldehyde and mal...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • European journal of medicinal chemistry

دوره 44 3  شماره 

صفحات  -

تاریخ انتشار 2009