2-Arylimidazo[1,2-a]pyridine-3-acetamide derivatives, preparation methods and uses thereof

A technology of acetamide and 2-a, applied in the field of medicine and chemical industry, can solve the problems of low bioavailability, poor pharmacokinetic properties, difficult to penetrate the blood-brain barrier and the like

Active Publication Date: 2011-12-28
INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most compounds generally have disadvantages such as poor pharmacokinetic properties, low bioavailability, and difficulty in penetrating the blood-brain barrier.

Method used

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  • 2-Arylimidazo[1,2-a]pyridine-3-acetamide derivatives, preparation methods and uses thereof
  • 2-Arylimidazo[1,2-a]pyridine-3-acetamide derivatives, preparation methods and uses thereof
  • 2-Arylimidazo[1,2-a]pyridine-3-acetamide derivatives, preparation methods and uses thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0135] Embodiment 1: 2-arylimidazo[1,2-a]-pyridine-3-acetic acid (V 1 )Synthesis

[0136] a) 2-(4-methoxyphenyl)-7-methylimidazo[1,2-a]pyridine (II 1 ) : Weigh 15.02g (0.1mol) of 4-methoxyacetophenone and dissolve it in 50mL of methanol, add 0.7g (0.005mol) of anhydrous aluminum trichloride, stir in an ice-water bath, add dropwise 16.16g (5.2mL, 0.101mol) of liquid bromine, (the color fades immediately, and a white solid precipitates when the dripping is finished), after the addition is completed, stir for another 20 minutes, add 25mL of water, add 13.5g (0.127mol) of sodium carbonate solid, and then add 11.5g (0.106mol) ) 2-amino-4-picoline solid, warming up to 35°C, stirring overnight (14h), to stop the reaction. Add 100mL of water, stir in an ice-water bath (a white solid precipitates out), filter with suction, wash with water, and dry to obtain II 1 20.28g, yellow solid powder, yield 85%. m.p.157~160℃.

[0137] b) 1-(2-(4-methoxyphenyl)-7-methylimidazo[1,2...

Embodiment 2-6

[0140] Example 2-6: Compound V 2 -V 6 Synthesis

[0141] In embodiment 2-6, with reference to synthetic compound V in embodiment 1 1 The method for synthesizing the following compound V respectively 2 -V 6 .

[0142] 2-(4-Chlorophenyl)-7-methylimidazo[1,2-a]-pyridine-3-acetic acid (V 2 ) : Pale yellow solid powder, yield 20%. m.p.229~231℃, 1 H NMR (DMSO-d 6 , 400MHz) δ: 2.42(s, 3H), 4.17(s, 2H), 7.06(d, 1H, J=7.00Hz), 7.53(s, 1H), 7.57~7.62(m, 2H), 7.76~7.78 (m, 2H), 8.48 (d, 1H, J=7.00Hz), 12.96 (s, 1H).

[0143] 2-(4-methylphenyl)-7-methylimidazo[1,2-a]pyridine 3-acetic acid (V 3 ) : White solid powder, yield 61.6%. m.p.220~224℃(decomposition), 1 H NMR (DMSO-d 6 , 400MHz) δ: 2.35(s, 3H), 2.38(s, 3H), 4.08(s, 2H), 6.80(d, 1H, J=7.00Hz), 7.27~7.29(m, 2H), 7.36(s , 1H), 7.63~7.65 (m, 2H), 8.26 (d, 1H, J=7.00Hz).

[0144] 2-(3,4-dichloroacetophenone)-7-methylimidazo[1,2-a]pyridine-3-acetic acid (V 4 ) : Pale yellow solid powder, yield 63.8...

Embodiment 7

[0147] Embodiment 7: the synthesis of N-(arylmethyl) ethylamine

[0148] N-(4-pyridylmethyl)ethylamine (VI 1 ) 15.70g (0.147mol) of 4-pyridinecarbaldehyde was weighed and dissolved in 200mL of ethanol, under stirring in a cold water bath, 21g (0.296mol) of 65-70% ethylamine aqueous solution was added, and after 0.5h of reaction, TLC monitored that the reaction was almost complete. 5.6 g (0.148 mol) of sodium borohydride was carefully added several times in small amounts. After the addition was complete, 30 mL of water was added, and the reaction was carried out overnight (20 h). TLC monitoring showed that the reaction was complete. The solvent was evaporated, water was added, extracted with dichloromethane, washed with water and saturated brine successively, and dried over anhydrous sodium sulfate. The solvent was distilled off to obtain 30 g of yellow viscous liquid with a crude yield of 73.4%. 1 H NMR (CDCl 3 , 400MHz) δ: 1.14(t, 3H, J=7.00Hz), 2.66(q, 2H, J=7.00Hz...

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Abstract

Disclosed are 2-arylimidazo[1,2-a]pyridine-3-acetamide derivatives represented by formula I, their tautomer, racemate or optical isomer, their pharmaceutically acceptable salt, or their solvates, wherein R 1 , R 2 , R 3 and R 4 are defined as in the specification. Preparation methods of said compounds and use of said compounds in treating and / or preventing central nervous system disease associated with TSPO functional disorder

Description

technical field [0001] The invention belongs to the field of medicine and chemical industry, and relates to a compound represented by formula I, which is a 2-arylimidazo[1,2-a]pyridine-3-acetamide derivative. The present invention also relates to the preparation method of the compound of formula I, the composition containing the compound of formula I, and the application of the compound of formula I. [0002] Formula I Background technique [0003] Anxiety disorders are characterized by panic and recurrent anxiety as the main symptoms. When patients are in a state of mental disorder, their normal potential cannot be exerted, resulting in low work efficiency. Long-term illness will seriously affect the patient's physical and mental health and daily life, and even lead to serious consequences such as suicide. In addition, anxiety disorders are often accompanied by depressive symptoms in the later stage. According to statistics, patients with anxiety disorders currently acc...

Claims

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Application Information

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Patent Type & AuthorityApplications(China)
IPC IPC(8): C07D471/04A61K31/437A61K31/444A61K31/5377A61P25/00A61P35/00A61P37/02A61P25/24A61P25/22A61P25/18A61P25/28A61P25/04A61P25/08A61P25/30A61P25/20
CPCA61K31/437C07D471/04A61P25/00A61P25/04A61P25/08A61P25/18A61P25/20A61P25/22A61P25/24A61P25/28A61P25/30A61P35/00A61P37/02A61P43/00
Inventor杨日芳李云峰李永臻赵楠恽榴红秦娟娟冯忠耀张有志
OwnerINST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A