Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Diaryl and arylheteroaryl urea derivatives as modulators of the 5-HT2A serotonin receptor useful for the prophylaxis and treatment of disorders related therto

A 5-HT2A, receptor technology, used in biochemical equipment and methods, microbial assay/inspection, preparations for in vivo tests, etc.

Inactive Publication Date: 2015-01-07
ARENA PHARMA
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Both have antipsychotic effects, but typical treatment also includes concomitant motor-related side effects (extrapyramidal syndrome, eg lip twitching, tongue knotting, displacement movements, etc.)

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
  • Diaryl and arylheteroaryl urea derivatives as modulators of the 5-HT2A serotonin receptor useful for the prophylaxis and treatment of disorders related therto
  • Diaryl and arylheteroaryl urea derivatives as modulators of the 5-HT2A serotonin receptor useful for the prophylaxis and treatment of disorders related therto
  • Diaryl and arylheteroaryl urea derivatives as modulators of the 5-HT2A serotonin receptor useful for the prophylaxis and treatment of disorders related therto

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0614] for the active content of 125 Synthetic methods for I to be incorporated into target molecules include:

[0615] A. The Sandmeyer reaction and similar reactions - This procedure converts an aryl or heteroaryl amine to a diazonium salt, such as tetrafluoroborate, and subsequently uses Na 125 I convert it into 125 I labeled compound. Representative procedures are reported by Zhu, D.-G. and co-workers in J. Org. Chem., 2002, 67, 943-948.

[0616] B. Ortho-iodine of phenols [ 125 I] Reaction - This procedure allows the 125 I was incorporated in the ortho position of the phenol as reported by Collier, T.L. and co-workers, J. Labeled Compd. Radiopharm., 1999, 42, S264-S266.

[0617] C. use 125 I Substitution of Brominated Aryl and Heteroaryl - This method generally consists of a two-step process. The first step is: in trialkyltin halide or hexaalkylditin [eg (CH 3 ) 3 SnSn(CH 3 ) 3 ] in the presence of, for example, Pd-catalyzed reactions [ie, Pd(Pd(Ph 3 P) 4 )] ...

example 1

[0623] Example 1 Synthesis of Compounds of the Invention.

[0624] Compounds described in the present invention are synthesized in Figures 17 to 21 as well as Figures 29 to 34 , where the symbols have the same definitions as used throughout this disclosure.

[0625] The compounds of the present invention and their synthesis are further illustrated by the following examples. However, the following examples are provided to further illustrate the invention without limiting the invention to these particular examples. Compounds described herein (above and below) were named according to CS Chem DrawUltra Version 7.0.1, AutoNom version 2.2. In certain instances, common names are used and it is understood that such common names should be recognized by those skilled in the art.

[0626] Chemistry: on a Varian Mercury Vx-400 equipped with 4-nuclei automatic switchable probe and z-gradient or on a Varian equipped with QNP (Quad Nucleus Probe) or BBI (Broad Band Inverse) and z-gradi...

example 11

[0629] Example 1.1: Preparation of intermediate 3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-aniline.

[0630] To a stirred solution of 4-bromo-5-(2-methoxy-5-nitro-phenyl)-1-methyl-1H-pyrazole (1.799 g, 5.76 mmol) in EtOH (20 mL) was added SnCl 2 2H 2 O (5.306 g, 23.05 mmol, 4.0 equiv), the mixture was stirred at reflux for 2 hours, and the EtOH was removed under vacuum. The resulting solid was dissolved in EtOAc, 1N NaOH (30 mL) was added, and the mixture was stirred overnight. The white precipitate was filtered off through celite, and the aqueous phase was extracted with EtOAc (3 x 80 mL). with anhydrous MgSO 4 The combined organic phases were dried, filtered and evaporated. through SiO 2 The crude reaction mixture was purified by column chromatography (eluent: EtOAc / hexane = 1 / 3, then 1 / 1) to yield 3-(4-bromo-2-methyl-2H-pyridine as a white solid Azol-3-yl)-4-methoxy-aniline (1.430 g, 5.07 mmol, 88%): LCMS m / z (%) = 282 (M+H 79 Br, 98), 284 (M+H 81 Br, 100). 1 ...

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 relates to certain pyrazole derivatives of Formula (I) and pharmaceutical compositions thereof that modulate the activity of the 5-HT2A serotonin receptor. Compounds and pharmaceutical compositions thereof are directed to methods useful in the prophylaxis or treatment of platelet aggreagation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, reducing the risk of blood clot formation, asthma or symptoms thereof, agitation or a symptom, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de la Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorder, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, and sleep disorders, sleep disorders, diabetic-related disorders and the like. The present invention also relates to the method of prophylaxis or treatment of 5-HT2A serotonin receptor mediated disorders in combination with a dopamine D2 receptor antagonist such as haloperidol, administered separately or together.

Description

[0001] This application is the application number 200480021009.5, the application date is July 21, 2004, the applicant is Ainina Pharmaceutical Company, and the invention name is "for the prevention and treatment of related diseases and as a 5-HT2A serotonin receptor modulator. Aryl and aryl heteroaryl urea derivatives” is a divisional application of the Chinese invention patent application. technical field [0002] The present invention relates to certain diaryl and arylheteroaryl urea derivatives of formula (I) and pharmaceutical compositions thereof, which modulate 5-HT 2A Serotonin receptor activity. Compounds and pharmaceutical compositions thereof are directed to methods for preventing or treating the following diseases: platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina pectoris, stroke, atrial fibrillation, reducing the risk of thrombosis, asthma or its symptoms, agitation or symptom, behavioral disorder, drug-induc...

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 Patents(China)
IPC IPC(8): C12Q1/02C07D231/16C07D231/12C07D401/12C07D405/12A61K49/00A61K31/415A61K31/496A61K31/5377A61K31/454A61K31/4155A61P7/02A61P9/00A61P9/10A61P25/20
CPCC07D231/12C07D405/12A61K31/415C07D231/16C07D401/12A61K31/4155A61K31/454A61K31/496A61K31/5377A61P1/04A61P1/08A61P1/14A61P11/00A61P11/06A61P13/12A61P19/02A61P25/00A61P25/02A61P25/08A61P25/14A61P25/16A61P25/18A61P25/20A61P25/22A61P25/28A61P25/32A61P27/02A61P29/00A61P3/08A61P43/00A61P7/02A61P7/04A61P9/00A61P9/10A61P3/10
Inventor 布拉德利·特加登洪纳帕·贾亚库马尔李红梅索尼娅·斯特拉-普莱内特彼得·伊恩·多萨
Owner ARENA PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com