Benzimidazole substituted azole compound and applications thereof

A compound, C1-C3 technology, applied in the field of medicinal chemistry, can solve the problem of weak selectivity of kinase inhibitors

Active Publication Date: 2020-02-25
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, there is evidence that side effects of kinase inhibitors are related to their poor selectivity

Method used

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  • Benzimidazole substituted azole compound and applications thereof
  • Benzimidazole substituted azole compound and applications thereof
  • Benzimidazole substituted azole compound and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0279] N-(3-(1H-Benzo[d]imidazol-2-yl)-1H-pyrazol-5-yl)-4-(4-methylpiperazin-1-yl)benzamide (1)

[0280] Add tetrahydrofuran (10ml), acetonitrile (5mL), sodium hydride (0.17g, 7.1mmol) and methyl 1H-benzimidazole-2-carboxylate (0.422g, 2.4mmol) sequentially to a round bottom flask under ice-bath conditions , After stirring for 0.5h, the temperature was raised to reflux and kept for 6h. The reaction solution was poured into an ice-water mixture (30ml), and the pH was adjusted to 2. A yellow solid precipitated out, which was suction filtered and dried to obtain a crude product. After the crude product was subjected to column chromatography (PE:EA=1:1), 0.31 g of a yellow solid was obtained with a yield of 70%. MS[M-H] - 184.05.

[0281] Into a 50mL round-bottomed flask, the product from the previous step (0.31g, 1.67mmol), hydrazine hydrochloride (0.21g, 2mmol), triethylamine (0.44g, 4.4mmol) and ethanol (10ml) were sequentially added, and refluxed for 8h. The reaction solut...

Embodiment 2

[0284] N-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazol-5-yl)-4-(3-morpholinopropylamino)benzamide (2)

[0285] The preparation method is similar to (1). 1 H NMR (300MHz, CDCl 3 )δ12.84(s, 1H), 11.58(s, 1H), 10.23(s, 1H), 7.75(d, 2H), 7.61-7.55(m, 2H), 7.22(d, 2H), 6.80-6.74 (m, 2H), 6.42(s, 1H), 4.63(s, 1H), 4.04(t, 4H), 3.38(t, 2H), 3.28(t, 2H), 2.33(m, 6H).MS( m / z): [M-H] - 444.2.

Embodiment 3

[0287] N-(3-(6-cyano-1H-benzo[d]imidazol-2-yl)-1H-pyrazol-5-yl)-4-((1-methylpiperidin-4-yl) Amino) benzamide (3)

[0288] The preparation method is similar to (1). 1 H NMR (300MHz, CDCl 3 )δ12.86(s, 1H), 11.6(s, 1H), 10.35(s, 1H), 8.03(d, 1H), 7.87(d, 1H), 7.67-7.58(m, 3H), 6.81-6.74 (m, 2H), 6.55(s, 1H), 4.32(s, 1H), 3.16-3.05(m, 1H), 2.96-2.92(m, 2H), 2.37(s, 3H), 2.1-1.9(m , 4H), 1.74-1.63 (m, 2H). MS (m / z): [M-H] - 439.18.

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Abstract

The invention relates to the field of medicinal chemistry, and discloses a benzimidazole substituted azole compound and applications thereof, and specifically relates to a benzimidazole substituted azole compound and a preparation method thereof, a pharmaceutical composition containing the benzimidazole substituted azole compound, medical applications of the benzimidazole substituted azole compound and the pharmaceutical composition, and especially applications as FMS-like tyrosine kinase 3 inhibitors.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to benzimidazole substituted azole compounds, their preparation methods, pharmaceutical compositions containing these compounds and their medical applications. Background technique [0002] Leukemia is a malignant neoplastic disease of the hematopoietic system, and it is a hematological system tumor in which hematopoietic stem / progenitor cells undergo malignant lesions. Leukemia can be divided into two categories according to the natural course of the disease and the degree of cell proliferation in different stages: acute leukemia and chronic leukemia. According to the different types of proliferating leukemia cells, it can be divided into two categories: acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML). Among them, AML accounts for 60%-70% of newly diagnosed acute leukemia in adults, and shows an increasing trend year by year (Environmental Health Perspectiv...

Claims

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Application Information

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IPC IPC(8): C07D401/14C07D403/12C07D405/14C07D413/14A61P35/00A61P35/02A61K31/5377A61K31/454A61K31/4184
CPCC07D403/12C07D413/14C07D401/14C07D405/14A61P35/00A61P35/02
Inventor 卢帅衡浩王淑贤王志杰向黎蔡炅桁秦天人田洁怡陈亚东陆涛
Owner CHINA PHARM UNIV
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