Unlock instant, AI-driven research and patent intelligence for your innovation.

Benzothiazin-4-one compound containing n-aminopiperazine fragment and preparation method thereof

A compound, piperazine technology, applied in the field of medicinal chemistry, can solve the problems of poor water solubility and in vivo activity of BTZ043 not as expected, and achieve the effects of low side effects, cost reduction, and simple operation of the synthesis process

Active Publication Date: 2022-06-21
MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Its representative BTZ043 has broad-spectrum anti-tuberculosis activity in vitro (Antimicrob Agent Chemother, 2010, 54(4): 1616-1618; 2012, 56(7): 3984-3985), but due to poor water solubility, the in vivo activity of BTZ043 Much worse than expected (EMBO MolMed, 2014, 6:372–383)

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Benzothiazin-4-one compound containing n-aminopiperazine fragment and preparation method thereof
  • Benzothiazin-4-one compound containing n-aminopiperazine fragment and preparation method thereof
  • Benzothiazin-4-one compound containing n-aminopiperazine fragment and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] Example 1. 2-(4-(Cyclohexylamino)piperazin-1-yl)-8-nitro-6-(trifluoromethyl)-4H-benzo[e][1,3]thiophene oxazin-4-one

[0066] Compound 1-tert-butyloxycarbonyl-4-aminopiperazine IV (201mg, 1.0mmol) was dissolved in 10mL of dichloromethane solution, then cyclohexanone (108mg, 1.2mmol) and acetic acid (72mg, 1.2mmol) were added , after stirring at room temperature for 0.5 hours, sodium triacetoxyborohydride (318 mg, 1.5 mmol) was added, and stirring was continued for 1.5 hours. Post-processing: the reaction solution was washed with water, and the dichloromethane layer was dried over anhydrous sodium sulfate.

[0067] After the above dried solution was filtered, trifluoroacetic acid (342 mg, 3.0 mmol) was added to the system, and stirred at room temperature for 1 hour. Post-processing: The reaction solution was directly spin-dried to carry out the next reaction.

[0068] The above concentrated solution was dissolved in 5 mL of methanol, then triethylamine (303 mg, 3.0 mmo...

Embodiment 2

[0070] Example 2. 2-(4-((cyclohexylmethyl)amino)piperazin-1-yl)-8-nitro-6-(trifluoromethyl)-4H-benzo[e][1, 3] Thiazin-4-one

[0071] Referring to Example 1, compound IV was reductively aminated with cyclohexylformaldehyde, de-Boc-protected, and then reacted with compound II to obtain a light yellow solid.

[0072] 1 H NMR (600MHz, CDCl 3 ):δ9.10(s,1H),8.76(s,1H),4.20-3.88(m,4H),2.78(brs,4H),2.66(d,J=6.7Hz,2H),1.78-1.66( m,5H),1.49-1.44(m,1H),1.28-1.16(m,3H),0.97-0.90(m,2H). 13 C NMR (150MHz, CDCl 3 ): δ166.61, 162.28, 144.08, 134.13, 133.57(q, J=4.1Hz), 129.94(q, J=35.3Hz), 126.81, 126.20(q, J=4.4Hz), 122.51(q, J=273.1Hz ),55.16,51.03,46.39,37.10,31.72,26.81,26.18.MS-ESI(m / z):472.2(M+H) + .

Embodiment 3

[0073] Example 3. 2-(4-((2-cyclohexylethyl)amino)piperazin-1-yl)-8-nitro-6-(trifluoromethyl)-4H-benzo[e][ 1,3] Thiazin-4-one

[0074] Referring to Example 1, compound IV was reductively aminated with cyclohexylacetaldehyde, de-Boc-protected, and then reacted with compound II to obtain a light yellow solid.

[0075] Yellow solid; yield: 27%; 1 H NMR (600MHz, CDCl 3 ): δ9.10(d, J=2.0Hz, 1H), 8.76(d, J=2.1Hz, 1H), 4.15-3.94(m, 4H), 2.85-2.79(m, 6H), 1.72-1.62( m,5H),1.38-1.30(m,4H),1.22-1.19(m,2H),0.95-0.89(m,2H). 13 C NMR (150MHz, CDCl 3): δ166.59, 162.28, 144.09, 134.11, 133.43(q, J=3.5Hz), 129.96(q, J=35.0Hz), 126.82, 126.05(q, J=3.4Hz), 122.52(q, J=273.5Hz ), 55.26, 46.22, 36.20, 35.91, 33.60, 29.84, 26.72, 26.45. MS-ESI (m / z): 486.2 (M+H) + .

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The present invention relates to a benzothiazin-4-ketone compound represented by formula (I), its preparation method and medical application, and an anti-tuberculosis drug composition using it as an active ingredient. More specifically, the present invention relates to a class of 6-trifluoromethyl-8-nitro-4H-benzo[e][1,3]thiazin-4-ketone compounds, whose 2-position substituent is N-aminopiperazine fragment, wherein the substituent R 1 and R 2 As shown in the manual.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and relates to benzothiazin-4-one compounds containing N-aminopiperazine fragments with anti-tuberculosis activity and their preparation methods, as well as anti-tuberculosis pharmaceutical compositions containing them; more specifically , the present invention relates to 6-trifluoromethyl-8-nitro-4H-benzo[e][1,3]thiazin-4-one compounds, whose 2-position substituent is N-aminopiperazine fragment . Background technique [0002] In recent years, tuberculosis (TB), especially the rising incidence of multidrug-resistant TB (MDR-TB) and the emergence of extensively drug-resistant TB (XDR-TB), has become a major public health and social issue of global concern. According to the World Health Organization (WHO), in 2015, there were 10.4 million new cases of TB worldwide, and 1.4 million people died of TB. In addition, nearly 1 / 3 of the world's population carries latent Mycobacterium tuberculosis, whi...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07D279/08A61K31/5415A61P31/06
CPCC07D279/08A61P31/06
Inventor 刘明亮汪阿鹏吕凯许世捷马超王奥雨秦晓瑜
Owner MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI