Unlock instant, AI-driven research and patent intelligence for your innovation.

Serotonin 5-ht2b inhibitory compounds

A compound, piperidine technology, applied in the field of serotonin 5-HT2B inhibitory compounds, can solve the problem of hERG having no affinity

Active Publication Date: 2021-11-09
ZOETIS SERVICE LLC
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The compounds of the present invention show a better safety profile than other known c5-HT2B antagonists because they have affinity for the c5-HT2B receptor but not hERG

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
  • Serotonin 5-ht2b inhibitory compounds
  • Serotonin 5-ht2b inhibitory compounds
  • Serotonin 5-ht2b inhibitory compounds

Examples

Experimental program
Comparison scheme
Effect test

example

[0324] The following examples provide a more detailed description of the process conditions for the preparation of compounds of the invention. It should be understood, however, that the invention is not intended to be limited to the details of the following modes of preparation, as fully described herein and claimed.

example 1

[0325] Example 1. (4-((1H-Imidazol-2-yl)amino)piperidin-1-yl)(4'-fluoro-[1,1'-biphenyl]-4-yl)methanone (Scheme 2 )

[0326]

[0327] step 1 . Preparation of tert-butyl 4-(1H-imidazol-2-ylamino)piperidine-1-carboxylate.

[0328] 4-Oxopiperidine-1-carboxylic acid tert-butyl ester (5g, 25.12mmol), 1H-imidazol-2-amine hydrochloride (4.48g, 37.68mmol), trimethylamine (10.31mL, 75.36mmol) and A mixture of titanium(IV) isopropoxide (15.22 mL, 50.24 mmol) was stirred in THF (100 mL) at 25°C overnight. Sodium cyanoborohydride (2.37 g, 37.68 mmol) and methanol (10 mL) were then added. The reaction mixture was maintained at 25°C for 4 hours. Water (100 mL) and ethyl acetate (100 mL) were added, the organic layer was separated and evaporated to give an oil. Purification by chromatography (5% methanol in DCM) afforded the title compound as a white solid.

[0329] step 2 . Preparation of 4-(1H-imidazol-2-amino)piperidine hydrochloride.

[0330] tert-Butyl 4-(1H-imidazol-2-ylami...

example 2

[0333] Example 2. (4-(1H-Imidazol-2-yl)piperidin-1-yl)(3'-(methylsulfonyl)-[1,1'-biphenyl]-4-yl)methanone (Scheme 3)

[0334]

[0335] step 1 . Preparation of methyl 3'-(methylthio)-[1,1'-biphenyl]-4-carboxylate

[0336] (3-Bromophenyl)(methyl)sulfonamide (1.5g, 7.38mmol) and (4-(methoxycarbonyl)phenyl)boronic acid (1.72g, 9.6mmol) in DMF (10mL) at 25°C Stir the solution, add K 3 PO 4 (4.69 g, 22.1 mmol). The reaction mixture was saturated with argon for 10 minutes. Add PdCl to it 2 (dppf)DCM (301 mg, 0.36 mmol) and stirred at 80°C for 16 hours. The reaction was monitored by TLC and LCMS. After the reaction was complete, it was diluted with water (100 mL) and extracted with ethyl acetate (2 x 100 mL). The organic portion was dried, concentrated, and the residue was purified by flash column chromatography (30% ethyl acetate in hexanes) to afford the title compound as a white solid.

[0337] step 2 . Preparation of methyl 3'-(methylsulfonyl)-[1,1'-biphenyl]-4-car...

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 compounds of the invention, as described herein, are novel serotonin 5-HT2B antagonists useful for the treatment of myxomatous mitral valve degeneration (MMVD), congestive heart failure (CHF), and / or asymptomatic heart failure in animals, preferably canine.

Description

technical field [0001] The present invention describes novel compounds that are serotonin 5-HT2B receptor antagonists and are useful in the treatment of mitral valve disease and congestive heart failure in animals. The invention also describes compositions comprising the compounds of the invention and methods of using the compounds to treat animals with mitral valve disease and congestive heart failure. Background technique [0002] The serotonin 5-HT2B receptor was originally characterized as a serotonin-derived G protein-coupled receptor controlling contraction of the rat gastric fundus (Clineschmidt et al., 1985, J. Pharmacol. Exp. Ther.", 235, 696). Since then, 5-HT2B has been detected in human tissues, including adipose tissue, central nervous system, heart, liver, intestine, lung, skeletal muscle, spleen and other organs and tissues (Kursar et al., 1994 , "Molecular Pharmacology (Mol.Pharmacol.), 46,227; Sanden et al., 2000, "Neurochem Int.", 36, 427-435; Borman et al...

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): C07D401/04C07D401/12C07D401/14C07D405/14C07D409/14A61K31/416A61K31/4178A61P25/00
CPCC07D401/04C07D401/12C07D401/14C07D405/14C07D409/14
Inventor R·A·艾文G·苏布拉马尼安邓金霞(南希)
Owner ZOETIS SERVICE LLC