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4-nitro-L-phenylalanine dipeptide derivatives as well as preparation method and applications thereof

A technology of nitrophenylalanine dipeptide and derivatives, which is applied in the field of dipeptide derivatives, can solve problems such as large side effects and unsatisfactory treatment effects, and achieve the effects of convenient post-processing, low cost, and mild reaction conditions

Inactive Publication Date: 2010-06-09
SOUTHWEST UNIVERSITY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] At present, there are many kinds of antidiabetic drugs, and the types are different. The clinically used type II diabetes treatment drugs mainly include sulfonylurea and non-sulfonylurea insulin secretagogues, biguanides, thiazolidinediones and other insulin sensitizers. , glycogenogenesis inhibitors, α-glucosidase inhibitors and new hypoglycemic drugs dipeptidyl peptidase-IV (DPP-IV) inhibitors, but the therapeutic effects of these drugs are not ideal or have relatively large side effects, so , the development of diabetes drugs with novel chemical structures, high efficiency and low toxicity is still an important task in the prevention and treatment of diabetes

Method used

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  • 4-nitro-L-phenylalanine dipeptide derivatives as well as preparation method and applications thereof
  • 4-nitro-L-phenylalanine dipeptide derivatives as well as preparation method and applications thereof
  • 4-nitro-L-phenylalanine dipeptide derivatives as well as preparation method and applications thereof

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Effect test

Embodiment 1

[0036] The preparation of embodiment 1, L-p-nitrophenylalanine (compound III)

[0037] L-p-nitrophenylalanine can be purchased directly from the market, or can be prepared by yourself. The present invention is prepared by the following improved method: in a round bottom flask, add a mixture of concentrated nitric acid and concentrated sulfuric acid with a volume ratio of 1:1.3, cool in an ice bath to a temperature of 0°C, and slowly add L-phenylalanine in batches , the molar ratio of L-phenylalanine to concentrated nitric acid is 1:1.3. After the addition is completed, the temperature is 0°C and the reaction is stirred for 60 minutes, and then the temperature is raised to room temperature and the reaction is stirred for 60 minutes. After the reaction is completed, a small amount of ice-water mixture is added and stirred. Cool to 0°C, adjust the pH to 6 with concentrated ammonia water in an ice bath, precipitate a large amount of precipitate, refrigerate, filter, wash the filte...

Embodiment 2

[0062] Embodiment 2, the preparation of L-p-nitrophenylalanine methyl ester hydrochloride (compound IV)

[0063] L-p-nitrophenylalanine methyl ester hydrochloride can be purchased directly from the market, or can be prepared by yourself. The present invention is prepared by the following improved method: add anhydrous methanol to a round bottom flask, cool in an ice bath to a temperature of 0°C, slowly add thionyl chloride, after the addition is completed, stir and react at a temperature of 0°C for 20 minutes, and add compound III in batches That is, L-p-nitrophenylalanine, stir until the raw material gradually dissolves into a white turbid liquid, then raise the temperature to 70°C and stir to react, it can be seen that all the raw materials are quickly dissolved and become a yellow clear liquid, and the reaction is monitored by thin layer chromatography (TLC) Process; After the reaction of L-p-nitrophenylalanine is completed, the vacuum rotary distillation is to dryness, the...

Embodiment 3

[0067] Embodiment 3, L-p-nitrophenylalanine dipeptide derivative Fmoc-AA-Phe (p-NO 2 )-OMe Preparation

[0068] General method: Dissolve Fmoc-AA-OH (20mmol) in 10mL of anhydrous THF, add HOBt (24mmol), DIC (24mmol) and DIPEA (20mmol) under ice bath and stirring, after the addition is complete, stir the reaction under ice bath for 30 ~60 minutes, monitor the generation of activated ester with TLC method; Dissolve compound IV, i.e., L-p-nitrophenylalanine methyl ester hydrochloride (20mmol) in 15mL of anhydrous THF, add DIPEA (30mmol), stir, Standby; mix the above two solutions, stir and react at room temperature, and monitor the reaction process by TLC method; after the reaction is completed, remove THF by distillation under reduced pressure, add 150 mL of water to the residual liquid, extract with 150 mL of ethyl acetate, and collect the water layer respectively and the organic layer, and the aqueous layer was extracted with 80mL of ethyl acetate, and all the organic layers w...

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Abstract

The invention discloses 4-nitro-L-phenylalanine dipeptide derivatives which have the general formula I disclosed in the specification. The detection indicates that the 4-nitro-L-phenylalanine dipeptide derivatives have favorable PPAR agonist activity and are excellent antidiabetic lead compounds. The 4-nitro-L-phenylalanine dipeptide derivatives can be further developed to prepare antidiabetic medicines, and have wide potential application prospects in the field of diabetes therapy. The invention also provides a preparation method of the 4-nitro-L-phenylalanine hydrate dipeptide derivatives, which comprises the step that 4-nitro-L-phenylalanine methyl ester hydrochlorides and protective amino acid are coupled under the action of a condensing agent. The preparation method has the advantages of mild reaction conditions, convenient post-treatment, high yield and low cost.

Description

technical field [0001] The invention relates to a dipeptide derivative, in particular to an L-p-nitrophenylalanine dipeptide derivative, and also relates to its preparation method and application in medicine. Background technique [0002] Diabetes mellitus (Diabetes Mellitus) is an endocrine and metabolic disease characterized by high blood sugar that seriously endangers health. It is the third largest non-communicable chronic disease in the world. According to the latest data from the International Diabetes Federation (IDF), there were approximately 239 million diabetics in the world in 2007. Diabetics are expected to reach 246 million in 2010 and 380 million in 2025, or 7.1% of the adult population. At present, the number of diabetic patients in China ranks second in the world and is expected to reach 59.31 million in 2025. In 2006, diabetes ranked the tenth cause of inpatients in China and the sixth cause of death among urban residents. Therefore, the prevention and tr...

Claims

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Application Information

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IPC IPC(8): C07K5/062C07K5/065C07K5/078C07K1/12A61K38/05A61P3/10
Inventor 杨大成晏菊芳刘建叶飞范莉陈欣孔令强蒋汉文汪林发张坤
Owner SOUTHWEST UNIVERSITY
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