Olanzapine derivative, preparation method and uses thereof

A derivative, olanzapine technology, applied in the field of olanzapine derivatives, can solve the problem of high price

Inactive Publication Date: 2020-01-10
成都阿奇生物医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But most of them are expensive, representative drugs include clozapine, risperidone, quetiapine etc.

Method used

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  • Olanzapine derivative, preparation method and uses thereof
  • Olanzapine derivative, preparation method and uses thereof
  • Olanzapine derivative, preparation method and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] The synthesis of embodiment 1 olanzapine derivative intermediate formula II

[0019] N 2 Under protection, the raw materials olanzapine (1.00g, 3.2mmol, 1eq), triethylamine (4.49mL, 32mmol, 10eq), and tetrahydrofuran (10mL) were sequentially added into a three-necked flask equipped with a thermometer and a stirrer. Cool in an ice bath to 5°C, add dropwise a solution of chloroacetyl chloride (0.510mL, 6.4mmol, 2eq) in tetrahydrofuran (5mL), monitor by TLC until the reaction is complete, stop the reaction, filter the reaction solution with suction, recover the solvent under reduced pressure, and use the residual solution for After washing with saturated sodium bicarbonate solution (30 mL) three times, the organic layer was taken and separated by column chromatography to obtain an intermediate, yellow powder, yield 40%, m.p.245-247°C.

[0020]

[0021] Synthesis of formula 1 intermediate formula II

[0022] Scheme 1Synthesis of intermediates

Embodiment 2

[0023] The preparation of embodiment 2 compound 1

[0024]

[0025] Add intermediate formula II (0.200g, 0.51mmol, 1eq), potassium carbonate (0.352g, 2.55mmol, 5eq), hexahydropyridine (1.01mL, 10.2mmol, 20eq) in a there-necked flask equipped with a thermometer and a stirrer, Tetrahydrofuran (20 mL) was used as a solvent, and the oil bath was heated to reflux. The completion of the reaction was monitored by TLC spotting, and the reaction was stopped. The solvent was recovered by rotary evaporation to obtain a yellow oil. Dichloromethane (10mL) dissolved the oily matter, washed with distilled water (30mL) three times, took the organic layer, recovered the solvent by rotary evaporation, and separated by column chromatography (ethyl acetate:methanol=20:1) to obtain the olanzapine hexahydropyridine derivative , yellow powder, yield 80%, m.p.262-263℃; 1 H NMR (400MHz, CDCl 3 )δ: 7.22(d, J=7.9Hz, 1H), 7.16(d, J=7.0Hz, 1H), 7.11(d, J=7.4Hz, 1H), 7.03(t, J=7.4Hz, 1H) ,6.45(s,1H),...

Embodiment 3

[0026] The preparation of embodiment 3 compound 2

[0027]

[0028] Add olanzapine derivative intermediate formula II (0.200g, 0.51mmol, 1eq), potassium carbonate (0.352mg, 2.55mmol, 5eq), tetrahydropyrrole (0.850mL, 10.2 mmol, 20eq), tetrahydrofuran (20mL) was used as a solvent, heated to reflux, and the reaction was monitored by TLC spotting, the reaction was stopped, cooled and left standing, and the solvent was recovered by rotary evaporation to obtain a yellow oil. Dichloromethane (10mL) dissolved the oil, washed three times with distilled water (30mL), took the organic layer, concentrated, and separated by column chromatography (ethyl acetate: methanol: 20:1) to obtain olanzapine tetrahydropyrrole derivatives, yellow Powder, yield 71%, melting point 235-235°C; 1 H NMR (400MHz, CDCl 3 )δ: 7.25 (d, J = 7.5Hz, 1H), 7.17 (dd, J = 14.3, 7.8Hz, 2H), 7.06 (t, J = 7.5Hz, 1H), 6.48 (s, 1H), 3.54 ( ddd, J=26.1, 22.5, 17.2Hz, 6H), 2.68–2.28(m, 14H), 1.88–1.66(m, 4H); 13 CNMR...

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Abstract

The invention discloses an olanzapine derivative, which has a structural formula represented by a formula I. The invention also provides a preparation method and applications of the olanzapine derivative. Compared with olanzapine, the olanzapine derivative of the invention can improve the survival rate of cells and significant reduce apoptosis index.

Description

technical field [0001] The invention relates to an olanzapine derivative, which belongs to the field of medicines. Background technique [0002] In recent years, with the acceleration of the pace of life, people's pressure has further increased. Schizophrenia and cancer have become diseases that cannot be ignored in today's society, seriously affecting the normal development of society and normal public order. [0003] The etiology of schizophrenia is relatively complex, most of its patients onset in young adults, and most patients have similar performance of system disorders. Through a large number of clinical observations, it is found that these obstacles are mainly manifested in the following aspects, such as the level of perception, the level of thinking and thinking, and the aspects of emotional expression and conscious behavior, especially the mental activities of patients and the surrounding environment Out of harmony with inner experience, even divorced from realit...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D495/04A61P25/18A61P25/00
CPCA61P25/00A61P25/18C07D495/04
Inventor 陈方石万棋牛春黎勇曹婷婷杨子耀
Owner 成都阿奇生物医药科技有限公司
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