Paliperidone amino acid derivatives and application thereof

An alkyl and methyl technology, applied in the field of paliperidone amino acid derivatives and its application, can solve problems such as weight gain

Active Publication Date: 2015-01-21
NHWA PHARMA CORPORATION +1
View PDF3 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, at the same time paliperidone has an effect on the histamine receptor H 1 and adrenergic alpha 1 The receptor also h

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Paliperidone amino acid derivatives and application thereof
  • Paliperidone amino acid derivatives and application thereof
  • Paliperidone amino acid derivatives and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0056] Embodiment 1, 3 (2 (4 (6 fluoro benzisoxazole) 3 piperidinyl) ethyl) 2 methyl 4 oxygen 6, 7, 8, 9-tetrahydro-4H-pyrido[1,2-a]9-pyrimidinyl-4-aminobutyrate hydrochloride

[0057] (1) Take 4-aminobutyric acid (10.3g, 100mmol), add it to the reaction flask, add 50ml water and 100ml acetone, add triethylamine (110mmol), stir at room temperature until all is dissolved, add Boc in batches Acid anhydride (26.2g, 120mmol), react at room temperature for 4h. Stop the reaction, evaporate the acetone under reduced pressure, extract with ether 50ml×2, discard several layers, adjust the pH of the aqueous layer to 4-5 with 10% dilute hydrochloric acid, extract with ethyl acetate 200ml×3, combine several layers , Dried with anhydrous magnesium sulfate, filtered, and spin-dried the filtrate to obtain 18.5 g of colorless oil, with a yield of 91.1%. MS(ESI)m / z204.2([M+H] + ).

[0058] (2) Take 2.0g (10mmol) of the product of the first step, add 50ml of dichloromethane, add 3.4g (9mmol) of p...

Example Embodiment

[0060] Example 2, 3 (2 (4 (6 fluoro benzisoxazole) 3 piperidinyl) ethyl) 2 methyl 4 oxygen 6, 7, 8, 9-tetrahydro-4H-pyrido[1,2-a]9-pyrimidinyl-3-(aminomethyl)-5-methylhexanoate hydrochloride

[0061] Using 3-aminomethyl-5-methylhexanoic acid instead of 4-aminobutyric acid, the target compound 2 was prepared according to the method of Example 1.

[0062] The structural formula of target compound 2 is shown in Table 1, melting point: 185-187°C. 1 H NMR(DMSO)δ11.15(s,1H), 8.19-8.23(m,1H), 7.69-7.73(m,1H), 7.30-7.35(m,1H), 5.68(t,J=8Hz,2H ), 3.95-3.98 (m, 1H), 3.71-3.76 (m, 3H), 3.45-3.51 (m, 4H), 3.11-3.18 (m, 4H), 2.92-2.96 (m, 1H), 2.51-2.56 (m, 4H), 2.51 (s, 2H), 2.38-2.40 (m, 2H), 2.31 (s, 3H), 2.23-2.27 (m, 2H), 1.72-1.99 (m, 7H), 1.02 (d ,J=6.6Hz,6H). MS(ESI)m / z568.3([M+H] + ).

Example Embodiment

[0063] Example 3, 3 (2 (4 (6 fluoro benzisoxazole) 3 piperidinyl) ethyl) 2 methyl 4 oxygen 6, 7, 8, 9-tetrahydro-4H-pyrido[1,2-a]9-pyrimidinyl-4-amino-2-methylbutyrate hydrochloride

[0064] Using 4-amino-2-methylbutyric acid instead of 4-aminobutyric acid, the target compound 3 was prepared according to the method of Example 1.

[0065] The structural formula of target compound 3 is shown in Table 1, melting point: 188-189°C. 1 H NMR(DMSO)δ11.20(s,1H), 8.17-8.20(m,1H), 7.70-7.76(m,1H), 7.29-7.33(m,1H), 5.70(t,J=8Hz,2H ), 3.89-3.92 (m, 1H), 3.72-3.77 (m, 3H), 3.45-3.51 (m, 4H), 3.14-3.18 (m, 4H), 2.95-2.99 (m, 1H), 2.51-2.57 (m, 4H), 2.38-2.41 (m, 2H), 2.99 (s, 3H), 2.23-2.27 (m, 3H), 1.92-1.99 (m, 5H), 1.43 (d, J=6Hz, 2H) . MS(ESI)m / z526.3([M+H] + ).

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The present invention belongs to pharmaceutical chemistry field. Paliperidone amino acids derivates and use thereof are disclosed After experiment, it is found that the compounds can be used for preparing medicant for treating mental diseases.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to paliperidone amino acid derivatives and applications thereof. Background technique [0002] Schizophrenia is the most serious and harmful disease among all mental diseases, with a global incidence of about 1‐2%. Patients with schizophrenia have a lifetime prevalence of 0.7-0.8%, with no apparent relationship to sex, race, or social boundaries, and a mortality rate 2-3 times higher than in the general population. The latest research shows that the social burden of mental illness ranks first among diseases in China, surpassing diseases such as cardiovascular and cerebrovascular diseases, respiratory system and malignant tumors. [0003] There are two main categories of existing schizophrenic drugs: typical anti-schizophrenic drugs and atypical anti-schizophrenic drugs. Typical antipsychotics (eg, chlorpromazine and haloperidol) block dopamine D 2 receptor, and has ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07D471/04A61K31/519A61P25/18A61P25/22A61P25/24
CPCC07D471/04A61P25/18A61P25/22A61P25/24
Inventor 张桂森陈寅孙家权徐祥清于民权刘欣刘笔锋
Owner NHWA PHARMA CORPORATION
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap