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Synthesis and application of a kind of phenylpyridazinone derivatives

A technology of phenyl and pyridazine, which is applied in the field of phenylpyridazine derivatives and its application in the treatment of mental and nervous diseases, and can solve the problems of EPS side effects, QT gap prolongation, and low ratio

Active Publication Date: 2022-04-22
NHWA PHARMA CORPORATION +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Typical antipsychotic drugs generally have severe EPS side effects and are ineffective for one-third of schizophrenic patients
[0005] After the 1960s, a series of new-generation antipsychotic drugs were successively developed, including ziprasidone (Ziprasidone), risperidone (Risperidone), etc., which are called second-generation antipsychotic drugs, namely new antipsychotic drugs Although their respective pharmacological effects are not exactly the same, they have common pharmacological characteristics, that is, they are sensitive to 5-hydroxytryptamine (5-HT) receptors (5-HT1A, 2A, 2c) and norepinephrine (NA) The affinity of the body (α1, α2) is much higher than that of the D2 receptor, resulting in a lower ratio of D2 / 5-HT2A
Compared with the first-generation antipsychotic drugs, its clinical effect has more advantages. It is not only as effective as traditional antipsychotic drugs for positive symptoms, but also effective for negative symptoms and cognitive deficit symptoms, and has a wider spectrum of action. However, these drugs have QT Adverse effects such as gap prolongation, hyperprolactinemia and weight gain

Method used

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  • Synthesis and application of a kind of phenylpyridazinone derivatives
  • Synthesis and application of a kind of phenylpyridazinone derivatives
  • Synthesis and application of a kind of phenylpyridazinone derivatives

Examples

Experimental program
Comparison scheme
Effect test

specific Embodiment approach

[0100] The following examples are for illustrative purposes only and are not intended to limit the invention.

[0101] A. Examples of Synthetic Aspects

Embodiment 1

[0102] Example 1, 2-(3,4-dichlorophenyl)-6-(3-(4-(4-methoxyphenyl)piperazin-1-yl)propoxy)pyridazine-3( 2H)-ketone

[0103] Reaction 1

[0104]

[0105] 1) Dissolve 14.5 g of phenylhydrazine hydrochloride and 9.8 g of maleic anhydride in 200 ml of purified water. Under stirring, 40 ml of concentrated hydrochloric acid was slowly added, and after the addition was completed, the mixture was heated to reflux and reacted for 6 hours. After the reaction was completed, the mixture was cooled in an ice-water bath, and a yellow solid was precipitated. Suction filtration, and the filter cake was washed twice with water. Remove the filter cake with saturated NaHCO 3 After dissolving, insoluble matter was filtered off, and the clear liquid was adjusted to pH 2-3 with concentrated hydrochloric acid, and a white solid was precipitated. After suction filtration and drying, 17.3 g was obtained, with a yield of 92.0%.

[0106] 2) Take 9.4g of the first step product, 13.8g of anhydrous ...

Embodiment 2

[0109] Example 2, 2-(3,4-dichlorophenyl)-6-(3-(4-(2-methoxyphenyl)piperazin-1-yl)propoxy)pyridazine-3( 2H)-ketone

[0110] Substituting 2-methoxyphenylpiperazine hydrochloride for 4-methoxyphenylpiperazine hydrochloride, the target compound was prepared according to the method of Example 1.

[0111] 1 H NMR (600MHz, CDCl 3 )δ7.89(d,J=2.5Hz,1H),7.65(dd,J=8.7,2.5Hz,1H),7.51(d,J=8.7Hz,1H),7.06–6.98(m,3H), 6.98–6.89(m, 2H), 6.87(dd, J=8.1, 1.1Hz, 1H), 4.26(t, J=6.4Hz, 2H), 3.87(s, 3H), 3.12(s, 4H), 2.70 (s,4H),2.63–2.51(m,2H),2.09–1.94(m,2H).MS(ESI)m / z489.1([M+H] + )

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PUM

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Abstract

The invention relates to the field of medicine, in particular, the invention relates to a phenylpyridazine derivative and its application. Specifically, the present invention relates to phenylpyridazinone derivatives, a pharmaceutical composition containing the phenylpyridazinone derivatives, and the preparation of the composition and the pyridazinone derivatives in the prevention or treatment of psychoneurological diseases the use of. Pyridazinone derivatives have the structure of formula (I). It has been found through experiments that this type of compound can be used to prevent or treat mental and nervous diseases.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a phenylpyridazine derivative and its application in the treatment of mental and neurological diseases. Background technique [0002] Schizophrenia is a disease characterized by deep cognitive and emotional splits, manifested in the impact of the most basic human behaviors, such as language, thought, perception and self-perception. The symptoms of the disease cover a wide range, the most common of which are mental disorders, such as hallucinations, paranoia, and delusions. [0003] Schizophrenia is the most serious mental illness, affecting approximately 1% of people worldwide, and only 5% of all patients who receive treatment eventually recover fully. In addition, because schizophrenia often leads to comorbidities, such as anxiety disorders, depression, or psychotropic substance abuse, according to a survey by Datamonitor, more than one-third of schizophrenia suff...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D237/16C07D413/14C07D403/12C07D405/12C07D401/14C07D417/14C07D417/12C07D409/14C07D401/12A61K31/506A61K31/501A61P25/18
CPCC07D237/16C07D401/12C07D401/14C07D403/12C07D405/12C07D409/14C07D413/14C07D417/12C07D417/14
Inventor 张桂森曹旭东张译芳邱印利赵松徐祥清刘欣刘笔锋
Owner NHWA PHARMA CORPORATION
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