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

A technology of formyl amino acid benzyl ester and amino acid benzyl ester is applied to 3H-imidazopyridine-6-formyl amino acid benzyl ester, its synthesis, anti-tumor activity and application fields, and can solve the problem of low toxic and side effects and anti-tumor drug efficacy. Not ideal, high toxicity problem

Inactive Publication Date: 2015-05-27
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 on new anti-tumor drugs with good curative effect and low toxicity and side effects has always been one of the hot spots in drug research.

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 bottom flask under ice bath, add 30mL of distilled water, then add 2mL of concentrated sulfuric acid drop by drop, stir evenly, add 10mL of formaldehyde solution (40%) after completely dissolved , react at 60°C for 8 hours. The reactant was cooled to room temperature, and the pH was adjusted down to 6 with concentrated ammonia water in an ice bath, and a large amount of white precipitates precipitated out. Filtered. The filter cake was washed with water and dried to afford 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 methyl 6S-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-6-carboxylate (3)

[0022] Add 100mL methanol to a 500mL eggplant bottle under ice-cooling, slowly add 10mL thionyl chloride dropwise with a constant pressure funnel, and add 5g (30mmol) 6S-4,5,6,7-tetrahydro-3H-imidazo[ 4,5-c]pyridine-6-carboxylic acid (2), reacted at room temperature for 3 days, the reaction was complete as monitored by TLC, 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 drained with diethyl ether and repeated 3 times to obtain a colorless powder, and finally recrystallized from methanol / diethyl 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 3H-imidazo[4,5-c]pyridine-6-carboxylic acid methyl ester (4)

[0024] Add 2g (7.9mmol) 6S-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-6-carboxylic acid methyl ester to 100mL eggplant bottle under ice bath, add DMF to dissolve. 1 mL of triethylamine was added dropwise to the solution to adjust the pH to 8, and 1.5 g (9.4 mmol) of potassium permanganate was added three times. After reacting for 6 hours, TLC monitored the completion of the reaction. The reactant was concentrated to dryness under reduced pressure, and the obtained black solid was dissolved in 1N HCl solution, and 2N NaOH solution was added dropwise under ice cooling to adjust the pH to 7, and a large amount of colorless solid was precipitated. The solid was purified on a silica gel column with 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 (in the formula, AA is selected from L-Ser residue, L-Glu(OBzl) residue base, L-Phe residue, L-Val residue, L-Arg (NO 2 ) residues, L-Tyr residues, L-Ala residues, L-Trp residues, L-Asn residues, L-Met residues, L-Ile residues, Gly residues, 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 four tumor cell lines HT-29, K562, A549, and HL60, and further related to their effects on S180-bearing small Inhibition of tumor growth in mice, and the present invention therefore relates to their use as antineoplastic agents. The invention belongs to the field of biomedicine. [0002] Background technique [0003] World Health Organization (WHO) officials stated at the "International Oncology" annual meeting held i...

Claims

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Application Information

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Patent Type & Authority Patents(China)
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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