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1,3-diaryl-3-aryl amidine-1-acetoxime compounds, preparation method and use thereof

An acetone oxime and compound technology, applied in the field of medicinal chemistry, can solve the problems of gastrointestinal discomfort, tumor volume increase, rise and the like

Inactive Publication Date: 2008-08-27
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are many problems to be solved in the anti-androgen drugs currently on the market: First, patients will experience various side effects after taking them, such as gastrointestinal discomfort, nausea, vomiting, insomnia, fatigue, headache, anxiety, blurred vision, loss of libido and Liver toxicity, etc.; secondly, patients with benign prostatic hyperplasia / prostate cancer will experience "anti-androgen hypofunction syndrome" after taking a single anti-androgen drug, which is manifested as a rapid increase in the originally suppressed prostate-specific antigen level , Tumor volume increases, can only stop taking the drug or switch to other anti-androgen drugs

Method used

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  • 1,3-diaryl-3-aryl amidine-1-acetoxime compounds, preparation method and use thereof
  • 1,3-diaryl-3-aryl amidine-1-acetoxime compounds, preparation method and use thereof
  • 1,3-diaryl-3-aryl amidine-1-acetoxime compounds, preparation method and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Example 1 Preparation of 1-(4-nitrophenyl)-3-phenyl-3-(4-chloroanilino)-1-acetone oxime

[0028]

[0029] Add 1.06 g (0.01 mol) of benzaldehyde, 1.28 g (0.01 mol) of 4-chloroaniline and 18 ml of absolute ethanol in the reaction flask, stir at room temperature for 10 minutes, then add 1.65 g (0.01 mol) of 4-nitroacetophenone And catalytic amount of concentrated hydrochloric acid, stirred at room temperature; the precipitated solid was filtered by suction and washed with absolute ethanol. The obtained solid was suspended in 20ml ethanol and washed with saturated NaHCO 3 The aqueous solution was neutralized to alkaline, filtered with suction, and the filter cake was washed with a small amount of absolute ethanol. The crude product was recrystallized in a mixed solvent of ethanol / water (volume ratio 1:1) to obtain 3.43 g of a light yellow powder solid, with a yield of 83%.

[0030] 1.9 grams (5 mmol) of the above-mentioned solid and 20 ml of ethanol were added to the re...

Embodiment 2

[0031] Example 2 Preparation of 1-(4-methylphenyl)-3-(2-thienyl)-3-(4-chloroanilino)-1-acetone oxime

[0032]

[0033] The operation process is the same as in Example 1, except that benzaldehyde is replaced by 2-thiophene formaldehyde, and 4-nitroacetophenone is replaced by 4-methylacetophenone to obtain white crystals with a yield of 85.6%; mp117~119°C; 1 H-NMR (400MHz, CDCl 3 )δ: 7.44(d, 2H, J=8.4Hz), 7.19(d, 2H, J=8Hz), 7.16(d, 1H, J=4.4Hz), 6.99(m, 3H), 6.92(t, 1H , J=3.6Hz), 6.39(d, 2H, J=8.4Hz), 4.89(dd, 1H, J=4.4Hz), 3.69(dd, 1H, J 1 =13.6Hz,J 2 =10Hz), 3.11(dd,1H,J 1 =13.6Hz,J 2 =4.4Hz), 2.38(s, 3H); ESI-MS m / z: 404.2(M + +H+MeOH).

Embodiment 3

[0034] Example 3 Preparation of 1-(4-methylphenyl)-3-phenyl-3-(4-chloroanilino)-1-acetone oxime

[0035]

[0036] The operation process is the same as in Example 1, except that 4-nitroacetophenone is replaced by 4-methylacetophenone to obtain light yellow crystals with a yield of 93.4%; mp156~158°C; 1 H-NMR (400MHz, CDCl 3 )δ: 7.48(d, 2H, J=8.4Hz), 7.38(d, 2H, J=6.8Hz), 7.32(t, 2H, J=7.2Hz), 7.26~7.20(m, 3H), 6.93( d, 2H, J=8.8Hz), 6.28(d, 2H, J=9.2Hz), 4.55(dd, 1H, J 1 =10.4Hz,J 2 =4Hz), 3.59(dd,1H,J 1 =13.6Hz,J 2 = 10.4Hz), 2.97(dd, 1H, J 1 =13.8Hz,J 2 =4Hz), 2.38(s, 3H); ESI-MS m / z: 365.9(M + +H).

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Abstract

The invention relates to a non-steroidal androgen receptor modulator compound containing 1, 3-diaryl-3-aromatic amine-1-acetoxime compound (I), or relative medical acceptable salt and a relative preparation method. The invention also relates to a drug compound of 1, 3-diaryl-3-aromatic amine-1-acetoxime compound (I) and relative medical acceptable salt. The1, 3-diaryl-3-aromatic amine-1-acetoxime compound (I) or relative medical acceptable salt has androgen receptor antagonistic activity, therefore, the compound can be used to prepare the non-steroidal drug for preventing or / treating prostatic hyperplasia, prostate cancer, hirsutism, serious androgen dependence alopecia and acne or the like.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and relates to 1,3-diaryl-3-arylamino-1-acetone oxime compound (I) and its preparation method, pharmaceutical composition and preparation for preventing or / and treating benign prostatic hyperplasia, Use in medicine for symptoms or diseases such as prostate cancer, hirsutism in women, severe androgen-dependent alopecia or acne. [0002] [0003] (where R 1 , R 2 , R 3 , R 4 Indicates H, halogen, C 1 ~C 12 Alkyl, C 3 ~C 7 Cycloalkyl, C 6 ~C 12 Aryl, C 1 ~C 12 Alkoxy, C 6 ~C 12 Aryloxy, C 1 ~C 12 Alkylthio, C 6 ~C 12 Arylthio, nitro, cyano, carboxyl, hydroxyl, CF 3 、NR 5 R 6 ; 5 , R 6 means H, C 1 ~C 12 Alkyl, C 6 ~C 12 Aryl; R 1 , R 2 , R 3 , R 4 Can be in any possible position of the benzene ring; R 1 , R 2 , R 3 , R 4 Can be the same or different; Ar represents phenyl, substituted phenyl, furyl, substituted furyl, thienyl, substituted thienyl, pyridyl, substit...

Claims

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Application Information

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IPC IPC(8): C07C251/48C07D333/36C07D307/52A61K31/15A61K31/341A61K31/381A61P13/08A61P35/00A61P17/00A61P17/14
Inventor 邓勇向玲沈怡周黎丽
Owner SICHUAN UNIV
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