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

2-Acylaminothiazole derivatives or salts thereof

A technology of thiazole and carbamoyl, applied in the field of 2-acylaminothiazole derivatives or their salts

Active Publication Date: 2019-12-31
ASAHI PHARMA CO LTD
View PDF8 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in these drugs, cholinergic side effects such as diarrhea, abdominal pain, and sweating are known

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
  • 2-Acylaminothiazole derivatives or salts thereof
  • 2-Acylaminothiazole derivatives or salts thereof
  • 2-Acylaminothiazole derivatives or salts thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0370] Hereinafter, the production method of the compound of formula (I) will be described in further detail based on the examples. It should be noted that the present invention is not limited to the compounds described in the following examples. In addition, the production method of the raw material compound is shown in the production example. In addition, the production method of the compound of the formula (I) is not limited to the production method of the specific examples shown below, and the compound of the formula (I) can also be produced by a combination of these production methods, or it is obvious to those skilled in the art method of manufacture.

[0371] In addition, in this specification, naming software, such as ACD / Name (registered trademark, Advanced Chemistry Development, Inc.), may be used for naming compounds.

[0372] In the measurement of powder X-ray diffraction, RINT-TTRII was used, and the measurement was carried out under the following conditions: th...

manufacture example 1

[0378] 4-[3-Fluoro-5-(trifluoromethyl)phenyl]-5-{[(2R)-2-methylpyrrolidin-1-yl]methyl}-1,3-thiazole-2 - A mixture of amine (1.0 g), 5-chloropyrazine-2-carboxylic acid (685 mg), COMU (1.9 g), dioxane (10 mL) and N,N-diisopropylethylamine (1.5 mL) Stir at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 5-chloro-N-(4-[3-fluoro-5-(trifluoromethyl)phenyl]-5-{[ (2R)-2-Methylpyrrolidin-1-yl]methyl}-1,3-thiazol-2-yl)pyrazine-2-carboxamide (800 mg).

manufacture example 2

[0380] 5-Chloropyrazine-2-carboxylic acid (1.7 g), N,N-dimethyl-4-aminopyridine (340 mg) and WSCD.HCl (2.1 g) were added to 5-{[(2R)-2 -Methylpyrrolidin-1-yl]methyl}-4-[4-(trifluoromethyl)thiophen-2-yl]-1,3-thiazol-2-amine (2.9g) and dichloromethane ( 60 mL) and stirred at 40 °C for 15 minutes. The reaction mixture was cooled to room temperature, diluted with chloroform, and washed with saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted with chloroform / methanol, and the organic layers were combined and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform-ethyl acetate) to obtain 5-chloro-N-(5-{[(2R)-2-methylpyrrolidin-1-yl]methyl}-4 as a solid -[4-(Trifluoromethyl)thiophen-2-yl]-1,3-thiazol-2-yl)pyrazine-2-carboxamide (2.4 g).

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

Provided are compounds useful as active ingredients of pharmaceutical compositions for treating urinary storage disorders, voiding disorders, and lower urinary tract diseases. The inventors have found that thiazole derivatives substituted at the 2-position of pyrazine carbonylamino are excellent muscarine M 3 receptor positive allosteric modulator, and it is expected to act as the same as muscarinic M 3 A prophylactic or therapeutic agent for bladder / urological diseases related to receptor-mediated bladder contraction, thereby completing the present invention. Expect 2-acylaminothiazole derivatives or salts thereof of the present invention as 3 A prophylactic or therapeutic agent for bladder / urological diseases related to receptor-mediated bladder contraction (such as voiding disorders such as hypoactive bladder).

Description

technical field [0001] The present invention relates to a kind of pharmaceutical composition, especially can be used as and muscarinic M 3 A 2-amidothiazole derivative or a salt thereof as an active ingredient of a pharmaceutical composition for the treatment of bladder / urinary diseases related to receptor-mediated bladder contraction. Background technique [0002] The important roles of the lower urinary tract are urine storage and urination, which are regulated by the synergistic action of the bladder and urethra. In other words, the smooth muscle of the bladder relaxes during urine storage, and the urethral resistance is maintained at a high state by the contraction of the urethral sphincter, thereby maintaining urination continence. On the other hand, the smooth muscle of the bladder contracts during urination, and at the same time the smooth muscle of the urethra relaxes, and the contraction of the external urethral sphincter is also inhibited. Disorders of the lower ...

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): C07D417/14A61K31/497A61P13/02A61P13/10A61P43/00
CPCC07D417/14A61K31/497A61P13/00A61P13/02A61P13/10A61P43/00A61K31/427
Inventor 高桥泰辅小池贵德根来贤二田中宏明前田纯横山和宏高松肇
Owner ASAHI PHARMA CO LTD
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