3H-imidazo[4,5-c]pyridine-6-formyl-amido acid benzyl esters and their synthesis, anti-tumor activity and use

A formyl amino acid benzyl ester and amino acid benzyl ester technology, applied in 3H-imidazopyridine-6-formyl amino acid benzyl ester, its synthesis, anti-tumor activity and application fields, can solve the problem of high toxicity and poor curative effect of anti-tumor drugs Ideal, low toxicity and side effects

Inactive Publication Date: 2013-12-18
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The clinical application of anti-tumor drugs has defects such as unsatisfactory curative effect and high toxicity, which makes research o

Method used

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  • 3H-imidazo[4,5-c]pyridine-6-formyl-amido acid benzyl esters and their synthesis, anti-tumor activity and use
  • 3H-imidazo[4,5-c]pyridine-6-formyl-amido acid benzyl esters and their synthesis, anti-tumor activity and use
  • 3H-imidazo[4,5-c]pyridine-6-formyl-amido acid benzyl esters and their synthesis, anti-tumor activity and use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] Example 1 Preparation of 6S-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-6-carboxylic acid (2)

[0020] Put 10.0g (0.064mol) L-histidine in a 250mL round-bottomed flask under ice bath, add 30mL distilled water, then add 2mL concentrated sulfuric acid dropwise, stir well, and add 10mL formaldehyde solution (40%) after complete dissolution , 60 ℃ reaction for 8 hours. The reactant was cooled to room temperature, and the pH was adjusted to 6 with concentrated ammonia water in an ice bath, and a large amount of white precipitate was precipitated. Filter. The filter cake was washed with water and dried to give 9.10 g (91%) of the title compound as a colorless powder. ESI-MS(m / z)167[M+H] + .

Embodiment 2

[0021] Example 2 Preparation of 6S-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-6-carboxylic acid methyl ester (3)

[0022] Add 100 mL of methanol to a 500 mL eggplant flask under ice bath, slowly add 10 mL of thionyl chloride dropwise with a constant pressure funnel, and add 5 g (30 mmol) of 6S-4,5,6,7-tetrahydro-3H-imidazo[ 4,5-c]pyridine-6-carboxylic acid (2) was reacted at room temperature for 3 days, TLC monitoring was completed, the reaction mixture was concentrated under reduced pressure, the residue was dissolved in methanol and concentrated under reduced pressure. This operation was repeated 3 times to obtain a white foamy solid, which was then dried with ether and repeated 3 times to obtain a colorless powder, which was finally recrystallized from methanol / ether to obtain 4.2 g (55%) of the title compound as a colorless solid. ESI-MS(m / z)181[M+H] + .

Embodiment 3

[0023] Example 3 Preparation of methyl 3H-imidazo[4,5-c]pyridine-6-carboxylate (4)

[0024] 2 g (7.9 mmol) of 6S-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-6-carboxylic acid methyl ester was added to a 100 mL eggplant flask under ice bath, and DMF was added to dissolve. To the solution, 1 mL of triethylamine was added dropwise to adjust the pH to 8, and 1.5 g (9.4 mmol) of potassium permanganate was added in three portions. After 6 hours of reaction, the completion of the reaction was monitored by TLC. The reactant was concentrated to dryness under reduced pressure, the obtained black solid was dissolved with 1N HCl solution, and 2N NaOH solution was added dropwise under ice bath to adjust the pH to 7, and a large amount of colorless solid was precipitated. The solid was purified on a silica gel column using dichloromethane / methanol as eluent, 0.93 g (66.4%) of the title compound as a colorless solid. ESI-MS(m / z)177[M+H] + .

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Abstract

The invention discloses 14 3H-imidazo[4,5-c]pyridine-6-formyl-amido acid benzyl esters shown in the general formula I. In the general formula I, AA represents L-Ser residue, L-Glu (OBzl) residue, L-Phe residue, L-Val residue, L-Arg residue, L-Tyr residue, L-Ala residue, L-Trp residue, L-Asn residue, L-Met residue, L-Ile residue, Gly residue, L-Asp (OBzl) residue or L-Leu residue. The invention discloses a preparation method of the 3H-imidazo[4,5-c]pyridine-6-formyl-amido acid benzyl esters, discloses HT-29, K562, A549 and HL60 tumor cell growth inhibition effects of the 3H-imidazo[4,5-c]pyridine-6-formyl-amido acid benzyl esters, further discloses S180-loading mice tumor growth inhibition effects of the 3H-imidazo[4,5-c]pyridine-6-formyl-amido acid benzyl esters, and also discloses use of the 3H-imidazo[4,5-c]pyridine-6-formyl-amido acid benzyl esters as antitumor drugs.

Description

Field of Invention [0001] The present invention relates to 15 kinds of 3H-imidazo[4,5-c]pyridine-6-formyl-amino acid benzyl esters represented by general formula I (where AA is selected from L-Ser residues, L-Glu(OBzl) residues base, L-Phe residue, L-Val residue, L-Arg (NO 2 ) residue, L-Tyr residue, L-Ala residue, L-Trp residue, L-Asn residue, L-Met residue, L-Ile residue, Gly residue, L-Asp(OBzl) residues, L-His residues and L-Leu residues), related to their preparation methods, related to their inhibitory effects on the proliferation of HT-29, K562, A549, HL60 four tumor cells, and further related to their effects on S180 small cells Inhibition of tumor growth in mice, thus the present invention relates to their use as antitumor drugs. The invention belongs to the field of biomedicine. [0002] Background technique [0003] Officials of the World Health Organization (WHO) stated at the "International Oncology" annual meeting held in Atlanta, USA in early 2009 that m...

Claims

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Application Information

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IPC IPC(8): C07K5/078A61K38/05A61P35/00
Inventor 彭师奇赵明王玉记吴建辉敖仕松
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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