A kind of substituted quinoline compound and its pharmaceutical composition

A compound and composition technology, applied in the field of medicine, can solve the problems of cholinesterase inhibitor side effects, unsatisfactory curative effect and the like

Active Publication Date: 2021-04-06
SHENZHEN TARGETRX INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, cholinesterase inhibitors can hav...

Method used

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  • A kind of substituted quinoline compound and its pharmaceutical composition
  • A kind of substituted quinoline compound and its pharmaceutical composition
  • A kind of substituted quinoline compound and its pharmaceutical composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1 Preparation of 5-d-3-benzenesulfonyl-8-piperazin-1-yl-quinoline (compound 10)

[0047]

[0048] Concrete synthetic steps are as follows:

[0049]

[0050] Step 1: Synthesis of compound 3.

[0051] Under nitrogen protection, N-iodosuccinimide (NIS, 6.88g, 30.58mmol) was added to the acetic acid solution (20mL) of 8-fluoroquinoline (compound 1, 3.0g, 20.39mmol), heated to 80°C and stirred overnight at this temperature. Add sodium sulfite (1.5g) and stir for 1 hour, then add iodine to quench the reaction, cool to room temperature after 1 hour, filter under low pressure, wash the crystals with acetic acid / water (1 / 2), and dry to obtain a yellow solid product Compound 3 3.5 g, the yield is 69%. LC-MS(APCI): m / z=293.9(M+1) + . 1 H NMR (300MHz, CDCl 3 ) (δ / ppm) 9.08 (d, J = 1.8 Hz, 1H), 8.58 (t, J = 1.8 Hz, 1H), 7.52-7.43 (m, 3H).

[0052] Step 2: Synthesis of Compound 5.

[0053] Under the protection of nitrogen, compound 4 (219mg, 2.49mmol) and cupro...

Embodiment 2

[0062] Example 2 Preparation of 3-benzenesulfonyl-8-(2,2,3,3,5,5,6,6-d8 piperazine)-1-yl-quinoline (compound 12)

[0063]

[0064] Concrete synthetic steps are as follows:

[0065]

[0066] Step 1: Synthesis of Compound 12.

[0067] Compound 5 (170 mg, 452 μmol) and potassium carbonate (38 mg, 3.17 mmol) were dissolved in 5 mL of n-propanol (n-PrOH), compound 11 (278 mg, 2.26 mmol) was added to the solution, heated to 95 ° C and Reacted for 17 hours, removed the solvent, added water and extracted with ethyl acetate, collected the organic phase and purified to obtain 25 mg of compound 12 as a yellow solid product with a yield of 15%. LC-MS(APCI): m / z=362.2(M+1) + . 1 H NMR (300MHz, CDCl 3 )(δ / ppm) 9.23(d, J=2.4Hz, 1H), 8.81(t, J=2.4Hz, 1H), 8.06-8.03(m, 2H), 7.65-7.56(m, 5H), 7.32- 7.29 (m, 1H).

Embodiment 3

[0068] Example 3 Preparation of 3-benzenesulfonyl-8-piperazin-1-yl-5,7-d2-quinoline (compound 13)

[0069]

[0070] Concrete synthetic steps are as follows:

[0071]

[0072] Step 1: Synthesis of Compound 13.

[0073] Compound 7 (130mg, 287μmol) was dissolved in deuterium water (5mL), deuterated hydrochloric acid (24μL, 287μmol, 12M / L) was added dropwise, heated to 180°C and microwaved for 2 hours, cooled to room temperature, poured into saturated Sodium bicarbonate solution was extracted with dichloromethane, and the organic phase was collected and purified by column to obtain 30 mg of compound 13 as a yellow solid product with a yield of 30%. LC-MS(APCI): m / z=353.3(M+1) + . 1 H NMR (300MHz, CDCl 3 )(δ / ppm) 9.22(d, J=2.4Hz, 1H), 9.05(d, J=2.4Hz, 1H), 8.10-8.07(m, 2H), 7.72-7.62(m, 4H), 3.25( t,J=4.5Hz, 4H), 2.96(t,J=4.5Hz, 4H).

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Abstract

The present invention discloses substituted quinoline compounds represented by formula (I) and compounds containing the compounds, or polymorphs, pharmaceutically acceptable salts, prodrugs, stereoisomers, isotopic variants, hydrates or Pharmaceutical compositions of solvates and uses thereof. The quinoline compound disclosed in the present invention and the composition comprising the compound can be used as 5-HT 6 The receptor antagonist has better properties of pharmacokinetic parameters and can be used to prepare a drug for treating Alzheimer's disease. (I).

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a quinoline compound, a composition containing the compound and uses thereof. Background technique [0002] 5-Hydroxytryptamine (5-HT) is a kind of vasoactive amine that widely exists in the body and acts on 5-HT receptors. According to the structure and function, 5-HT receptors can be divided into 7 families and 14 subtypes. Among them, the receptor subtypes involved in the learning and memory process mainly include 5-HT 1A , 5-HT 1B , 5-HT 2 , 5-HT 3 , 5-HT 5 , 5-HT 6 , 5-HT 7 Subtype. 5-HT is a relatively important monoamine neurotransmitter in the central nervous system, and participates in many physiological processes such as human sensory, motor and behavior. [0003] As a member of the 5-HT receptor family, 5-HT 6 The receptors are almost all located in the central nervous system, especially highly expressed in areas related to learning and memory, s...

Claims

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Application Information

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IPC IPC(8): C07D215/40C07B59/00A61K31/496A61P25/24A61P25/22A61P25/28A61P25/14A61P25/18A61P9/10A61P3/04
CPCA61K31/496C07B59/00C07D215/40
Inventor 王义汉李焕银
Owner SHENZHEN TARGETRX INC
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