Triazole compound, preparation method and application of triazole compound in preparation of medicine for preventing and treating cancer

A compound and drug technology, which is applied in the preparation of anticancer drugs. In the field of triazole compounds, it can solve the problems of high toxicity and side effects of drugs, and achieve the effect of alleviating the side effects and effectively inhibiting the activity of LSD1 protease

Active Publication Date: 2021-06-08
HEBEI KANGTAI PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these inhibitors are basically covalently bound drugs, which will be embedded in DNA, so the toxic side effects of drugs are relatively large

Method used

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  • Triazole compound, preparation method and application of triazole compound in preparation of medicine for preventing and treating cancer
  • Triazole compound, preparation method and application of triazole compound in preparation of medicine for preventing and treating cancer
  • Triazole compound, preparation method and application of triazole compound in preparation of medicine for preventing and treating cancer

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Embodiment 1: the preparation of compound 1

[0030]

[0031] The specific preparation method is:

[0032] 1) Preparation of compound (1-1):

[0033]

[0034] Dissolve 4-ethynylbenzoic acid (438mg, 3.00mmol) in DMF (15mL), add EDCI (863mg, 1.50mmol), HOBt (486mg, 1.20mmol), DIPEA (1.16g, 9.00mmol) N-methyl Basepiperazine (300mg, 3mmol), react at room temperature for 8h. The reaction solution was washed with saturated brine, extracted with ethyl acetate, the organic phase was dried and concentrated, and purified by column chromatography (dichloromethane:methanol=20:1) to obtain compound 1-1 (white solid, 554mg, 81%) .

[0035] The NMR test result of compound 1-1 is:

[0036] 1 HNMR (400MHz, CDCl 3 )δ7.51(d, J=8.3Hz, 1H), 7.35(d, J=8.3Hz, 1H), 3.78(s, 1H), 3.40(s, 1H), 3.14(s, 1H), 2.47( s,1H),2.30(s,2H).δ13C NMR(100MHz,CDCl 3 )δ169.6, 136.0, 132.3, 127.2, 123.7, 82.9, 78.8, 55.3, 54.8, 47.7, 42.2. HRMS (ESI) calculated for C 14 h 16 N 2 NaO + :251.1160,...

Embodiment 2

[0047] Embodiment 2: the preparation of compound 2

[0048]

[0049] The specific preparation method is:

[0050] 1) Preparation of compound (2-1):

[0051]

[0052] The specific preparation method is: similar to the preparation method of compound 1-1, the difference is that one of the raw materials used is 5-(piperazin-1-yl)pyrimidine, and an equimolar substitution of compound (1-1) in the preparation method of N-methylpiperazine.

[0053] The NMR test result of compound 2-1 is:

[0054] 1 H NMR (400MHz, CDCl 3 )δ8.29(d, J=4.9Hz, 2H), 7.52(d, J=7.9Hz, 2H), 7.37(d, J=8.0Hz, 2H), 6.51(t, J=4.8Hz, 1H) ,4.03–3.66(m,6H),3.54–3.38(m,2H),3.16(s,1H). 13 CNMR (100MHz, CDCl 3 )δ169.8, 161.5, 157.8, 135.8, 132.3, 127.2, 123.8, 110.6, 82.8, 79.0, 47.5, 44.0, 43.5, 42.2. HRMS (ESI) calculated for C 17 h 16 N 4 NaO + :315.1222,found 315.1224.

[0055] 2) Preparation of compound 2:

[0056] The specific preparation method is: similar to the preparation method of compound ...

Embodiment 3

[0059] Embodiment 3: the preparation of compound 3

[0060]

[0061] The specific preparation method is: similar to the preparation method of compound 1, the difference is that one of the raw materials used is compound 2-1, and N-methylpiperazine in the preparation method of compound (1-1) is replaced by equimolarity; One of the raw materials used, methoxydimethylbenzylmethanol, replaces 5-bromo-2-methoxybenzylmethanol in the preparation method of compound (1-2) by equimolarity.

[0062] The NMR test result of compound 3 is:

[0063] 1 H NMR (400MHz, CDCl 3 )δ8.30(d, J=4.7Hz, 2H), 7.86(d, J=8.0Hz, 2H), 7.73(s, 1H), 7.47(d, J=8.0Hz, 2H), 7.31(td, J=7.9,1.7Hz,1H),7.20(dd,J=7.7,1.6Hz,1H),6.89-6.97(m,2H),6.52(t,J=4.7Hz,1H),6.22(q,J =7.1Hz,1H),3.82(s,9H),3.51(s,2H),1.97(d,J=7.1Hz,3H). 13 C NMR (100MHz, CDCl 3 )δ170.4, 161.6, 157.8, 156.4, 146.3, 134.8, 132.6, 129.8, 128.1, 127.8, 126.9, 125.7, 121.0, 119.5, 110.9, 110.6, 55.6, 54.6, 47.6, 44.1, 42.HR, 6, 20. )

[0064] c...

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Abstract

The invention provides a compound shown as a formula (I) or pharmaceutically acceptable salt thereof. In the formula (I), Ar is selected from any one of a substituted aromatic ring group or a substituted aromatic heterocyclic group; R1 is selected from any one of H, alkane, aryl, CF3 and alkyl tertiary amine structures; R2 is selected from any one of H, alkane, aryl, CF3, F, Cl, Br and other halogen structures; and R3 and R4 are selected from any one of H, alkane, aryl, a cyclic structure and a substituted cyclic structure. The compound or the pharmaceutically acceptable salt thereof has an efficient and reversible effect of inhibiting the activity of LSD1 protease, and is expected to relieve the toxic and side effects of drugs.

Description

technical field [0001] The invention belongs to the field of chemical medicine, and in particular relates to a triazole compound, a preparation method and its application in the preparation of anticancer drugs. Background technique [0002] Epigenetics is a new discipline emerging in the post-genome era, and it is a concept corresponding to genetics. Genetics refers to changes in gene expression levels based on changes in gene sequence, such as gene mutation, gene heterozygosity loss, and microsatellite instability; while epigenetics is the study of gene expression without changes in genomic DNA sequence. A subdiscipline of genetics in which genetic changes result in heritable phenotypic changes. The main research contents of epigenetics include DNA methylation, histone modification, chromatin remodeling, non-coding RNA regulation, genomic imprinting, pseudogenes, RNA splicing, RNA editing, RNA interference, X chromatin inactivation, inclusion Sons, riboswitches, etc. Epi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D249/06C07D403/12A61K31/506A61K31/496A61P35/00
CPCC07D249/06C07D403/12A61P35/00
Inventor 李金岭
Owner HEBEI KANGTAI PHARMA
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