Benzo-isoxazol piperidine derivative and application in preparing analgesic and sedative medicaments

A technology of benzisoxazole piperidine and fluorobenisoxazole is applied to benzisoxazole piperidine derivatives and application fields in the preparation of analgesic and sedative drugs, and can solve the problem of poor treatment effect and inability to Meet clinical treatment requirements and other issues

Active Publication Date: 2010-06-30
NHWA PHARMA CORPORATION +1
View PDF0 Cites 9 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] However, currently developed 5-HT reuptake inhibitors and 5-HT 2A Antagonists still have some defects in analgesic effect and toxic side effects, such as 5-HT reuptake inhibition and 5-HT 2A Although the antagonist trazodone has definite curative effect on some persistent pains and its clinical effect is better than that of ibuprofen, it has poor therapeutic effect on other severe acute and chronic pains and is far from meeting the clinical treatment requirements; while nefazodone Now withdrawn from the market due to severe hepatotoxicity

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
  • Benzo-isoxazol piperidine derivative and application in preparing analgesic and sedative medicaments
  • Benzo-isoxazol piperidine derivative and application in preparing analgesic and sedative medicaments
  • Benzo-isoxazol piperidine derivative and application in preparing analgesic and sedative medicaments

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0097] Preparation of N-(2-(1-indolyl)ethyl)-4-(3-(6-fluorobenzoisoxazolyl))piperidine (II-1) hydrochloride

[0098] Using indole as a raw material, N-(2-chloroethyl)indole was prepared according to the synthesis and post-treatment methods in General Method 1. Take N-(2-chloroethyl)indole (1.0g, 0.0055mol), 4-(3-(6-fluorobenzoisoxazolyl))piperidine (1.10g, 0.005mol), DIPEA (2.58 g, 0.02mol) and KI (0.83g, 0.005mol) in 30ml of acetonitrile solution, reflux reaction for 12 hours, according to the post-treatment operation in General Method 1, 1.31g of white crystals were obtained with a yield of 65.5%. Melting point: 216-218°C.

[0099] Elemental Analysis: C 22 h 22 FN 3 O·HCl·H 2 O (Theoretical %: C 63.23, H 6.03, N 10.05, Cl 8.48; Experimental % C 63.15, H 6.021, N 10.08, Cl 8.51); MS: m / z 363.2 (M + )

[0100] 1 HNMR (DMSO-d 6 ): δ2.21~2.25(m, 2H), 2.34~2.44(m, 2H), 3.13~3.22(m, 2H,), 3.43~3.52(m, 3H), 3.63~3.67(m, 2H), 4.76 ~4.81(m, 2H), 6.50~6.52(d, 1H, J=3.2 Hz,),...

Embodiment 2

[0102] Preparation of N-(3-(1-indolyl)propyl)-4-(3-(6-fluorobenzoisoxazolyl))piperidine (II-2) hydrochloride

[0103] Using indole as raw material, N-(3-chloropropyl)indole was prepared according to the synthesis and post-treatment methods in General Method 1. Take N-(3-chloropropyl)indole (1.07g, 0.0055mol), 4-(3-(6-fluorobenzoisoxazolyl))piperidine (1.10g, 0.005mol), DIPEA (2.58 g, 0.02mol) and KI (0.83g, 0.005mol) in 30ml of acetonitrile solution, reflux reaction for 12 hours, according to the post-treatment operation in General Method 1, 1.28g of white crystals were obtained with a yield of 61.8%. Melting point: 209-211°C.

[0104] Elemental Analysis: C 23 h 24 FN 3 O·HCl·2H 2 O (Theoretical %: C 66.74, H 6.02, N 10.15, Cl 8.57; Experimental % C 66.70, H 6.01, N 10.12, Cl 8.55); MS: m / z 377.2 (M + )

[0105] 1 HNMR (DMSO-d 6 ): δ2.12~2.20(m, 2H), 2.21~2.25(m, 2H), 2.34~2.45(m, 2H), 3.14~3.22(m, 2H), 3.42~3.50(m, 3H)3.64~ 3.67(m, 2H), 4.77~4.80(m, 2H 2 ), 6.52-8....

Embodiment 3

[0107] Preparation of N-(4-(1-indolyl)butyl)-4-(3-(6-fluorobenzoisoxazole))piperidine (II-3) hydrochloride

[0108] Using indole as raw material, N-(4-chlorobutyl)indole was prepared according to the synthesis and post-treatment methods in General Method 1. Take N-(4-chlorobutyl)indole (1.14g, 0.0055mol), 4-(3-(6-fluorobenzoisoxazolyl))piperidine (1.10g, 0.005mol), DIPEA (2.58 g, 0.02mol) and KI (0.83g, 0.005mol) in 30ml of acetonitrile solution, reflux reaction for 16 hours, according to the post-treatment operation in General Method 1, 1.33g of white crystals were obtained, with a yield of 62.1%. Melting point: 201-203°C.

[0109] MS: m / z 391.2 (M + )

[0110] 1 HNMR (DMSO-d 6 ): 1.68~1.74(m, 2H), 1.79~1.85(m, 2H), 2.16~2.21(m, 2H), 2.27~2.37(m, 2H), 3.00~3.13(m, 4H), 3.41~3.48 (m, 1H), 3.53~3.57(m, 2H), 4.20~4.25(t, 2H, J=6.8Hz), 6.43(d, 1H, J=6.4Hz), 7.01(t, 1H, J=7.6 Hz), 7.13(t, 1H, J=7.6Hz), 7.33(td, 1H, J=9.2Hz, J=2.0Hz), 7.42(d, 1H, J=3.2Hz), 7.52(d, 1H, J=7.6...

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

PropertyMeasurementUnit
melting pointaaaaaaaaaa
melting pointaaaaaaaaaa
Login to view more

Abstract

The invention discloses a benzo-isoxazol piperidine derivative and an application in preparing analgesic and sedative medicaments. The compound has the antagonism of 5-HT2A and the mediation action of serotonin systems such as the reuptake inhibition of 5-HT, and the like. The derivative is the free alkali or salt of a compound having the structural general formula disclosed in the specification. Proved by pharmacological tests, the compound has good analgesic and sedative activities and smaller toxic and side effects. The structural general formula of the derivative is disclosed in the specification.

Description

technical field [0001] The invention relates to a novel benzoisoxazole piperidine derivative and its application in the preparation of analgesic and sedative drugs. Background technique [0002] Such as tumor pain, postoperative pain, and various recurrent severe acute and chronic pains have plagued tens of millions of patients and are currently a major clinical problem. The existing clinical analgesic drugs can be mainly divided into three categories: 1) non-steroidal anti-inflammatory analgesics 2) opioid analgesics 3) other non-opioid analgesics, mainly including: local anesthetics, antidepressants drugs, antiepileptic drugs, etc. For acute pain and cancer pain, currently opioid analgesics are mainly used clinically or supplemented with some non-steroidal anti-inflammatory analgesics. However, opioid analgesics have side effects such as addiction, respiratory depression, and decreased gastric motility, which limit their widespread use. In the treatment of various chron...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07D413/14A61K31/454A61P25/04A61P25/20
CPCC07D413/14A61P25/04A61P25/20A61P29/00
Inventor 李建其王冠张桂森吕娜焦广俊刘世成周世暇
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