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Pyrimido 1,2,4-triazole compound and its preparation method and application

A – technology of triazoles, compounds, applied in the field of medicinal chemistry

Active Publication Date: 2020-04-17
ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are no reports on linking pyrimido 1,2,4-triazole compounds with DCN1-UBC1 to play an anti-tumor effect, so this direction has very important research value

Method used

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  • Pyrimido 1,2,4-triazole compound and its preparation method and application
  • Pyrimido 1,2,4-triazole compound and its preparation method and application
  • Pyrimido 1,2,4-triazole compound and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0075] This embodiment provides a compound e1, the structural formula of the compound e1 is as follows:

[0076]

[0077] The preparation method of the compound e1 comprises the following steps:

[0078] (1) Preparation of Compound M Add 1g (about 8.61mmoL) of 2-amino-5-mercapto-1,2,4-triazole and 1.37g (about 12.92mmoL) of sodium carbonate into the reaction flask respectively, and then About 20 mL of acetone was added, 1.13 mL (about 9.47 mmoL) of benzyl chloride was slowly added dropwise, and the reaction was refluxed at 60° C., and the reaction was monitored by TLC. After the reaction was completed, suction filtration was performed directly, and the filtrate was subjected to column chromatography (dichloromethane:methanol=20:1) to obtain pure compound M. Calculation by measurement: the yield of compound M is about 67.57%. Appearance: white solid. 1 H NMR (400MHz, DMSO-d 6 )δ7.41-7.18(m,5H),4.34(s,2H); 13 CNMR (100MHz, DMSO-d 6 )δ152.19, 147.08, 136.55, 128.79, 128....

Embodiment 2

[0083] This embodiment provides a kind of compound e2, and the structural formula of this compound e2 is as follows:

[0084]

[0085] This embodiment provides the preparation method of the above-mentioned compound e2, which is basically the same as the preparation method of the compound e1 provided in Example 1.

[0086] The compound e2 is a white solid with a calculated yield of about 90.1% and a melting point of 201.4°C-203.7°C; 1 H NMR (400MHz, DMSO-d 6 )δ11.22(s,1H),6.82(s,1H),5.00(t,J=6.2Hz,2H),3.71(s,2H),3.21(t,J=7.1Hz,2H),2.81( s,6H),1.85–1.69(m,2H),1.02(t,J=7.3Hz,3H); 13 C NMR (100MHz, DMSO-d 6 )δ166.73, 164.35, 154.60, 146.05, 141.80, 108.38, 54.07, 43.09, 42.42, 32.52, 24.53, 22.49, 13.04; HRMS (ESI): m / z calcdfor C 14 h 22 N 9 S 2 (M+H) + , 380.14341; found, 380.14078; therefore, it can be determined that the structural formula of the compound e2 provided in this example is as shown above.

Embodiment 3

[0088] This embodiment provides a compound e3, the structural formula of the compound e3 is as follows:

[0089]

[0090] This embodiment provides the preparation method of the above-mentioned compound e3, which is basically the same as the preparation method of the compound e1 provided in Example 1.

[0091] The compound e3 is a white solid with a calculated yield of about 93.3% and a melting point of 174.2°C-175.8°C; 1 H NMR (400MHz, DMSO-d 6 )δ11.15(s,1H),6.82(s,1H),6.02(m,1H),5.38(d,J=17.0Hz,1H),5.16(d,J=10.0Hz,1H),5.00( t, J=6.2Hz, 2H), 3.92(d, J=6.8Hz, 2H), 3.70(s, 2H), 2.81(s, 6H); 13 C NMR (100MHz, DMSO-d 6 )δ166.01, 164.50, 154.59, 146.01, 141.98, 133.38, 118.50, 108.44, 54.07, 43.09, 42.41, 33.20, 24.55; HRMS (ESI): m / z calcd for C 14 h 20 N 9 S 2 (M+H) + , 378.12776; found, 378.12473; therefore, it can be determined that the structural formula of the compound e3 provided in this example is as shown above.

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Abstract

The invention provides a pyrimido-1, 2, 4-triazole compound. The pyrimido-1,2,4-triazole compound adopts a structural formula shown as a formula (I) or a formula (II), or a salt-forming compound of the compound shown as the formula (II), wherein in the formula (I), R1 represents alkyl or aryl, R2 represents a hydrogen atom or sulfydryl with a substituent, R3 represents a tetrazole group with a substituent and R4 represents a hydrogen atom or an alkyl substituent. The invention further provides a preparation method and application of the compound. The pyrimido-1, 2, 4-triazole compound providedby the invention can be prepared into a series of compounds with antitumor activity through bonding with a DCN1-UBC12 inhibitor and can also be applied to an antitumor medicine with DCN1-UBC12 as a target, so that a new way is opened up for finding the novel antitumor medicine targeting the DCN1-UBC12. In addition, a synthesis method of the pyrimido-1, 2, 4-triazole compound, provided by the invention, is feasible, and the yield is high.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and specifically relates to a compound of a pyrimido 1,2,4-triazole structural unit, a preparation method thereof, and an application thereof in preparing an antitumor drug targeting DCN1-UBC12. Background technique [0002] Tumor is a serious threat to human diseases. Although there are many anti-tumor drugs on the market, there are still some shortcomings in these drugs, such as relatively large toxic side effects, weak targeting, and easy drug resistance. Targeted drugs are not only effective but also have much less side effects than conventional treatments, so their research and development has received more and more attention. [0003] Ubiquitin can covalently bind and modify a variety of proteins in cells, making their polyubiquitylation recognized and degraded by the 26S proteasome. This post-translational modification of proteins has become a hot spot in cell molecular biology research....

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D487/04A61P35/00
CPCA61P35/00C07D487/04
Inventor 刘宏民余斌王帅赵丽杰郑一超
Owner ZHENGZHOU UNIV