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

Propofol analogs, process for their preparation, and methods of use

a technology of propofol and analogs, applied in the field of substituted dialkylphenol propofol compounds, can solve the problems of pain upon injection, reduced blood pressure, and relative high incidence of apnea

Inactive Publication Date: 2007-08-09
ABRAXIS BIOSCI LLC +1
View PDF11 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The invention provides new compounds called para-substituted dialkylphenol propofol derivatives and a method for making them. These compounds can be used as pharmaceutical agents to induce general anesthesia, sedation, and hypnotic or sleep effects.

Problems solved by technology

Disadvantages of propofol include a relatively high incidence of apnea, blood pressure reductions, and pain upon injection.

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
  • Propofol analogs, process for their preparation, and methods of use
  • Propofol analogs, process for their preparation, and methods of use
  • Propofol analogs, process for their preparation, and methods of use

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0061] This example illustrates the preparation of (4-fluorophenyl)-(4-hydroxy-3,5-diisopropyl phenyl)methanone (CT7). To a solution of 2,6-diisopropylphenol (3.3 g, 18.5 mmol) in 98 mL of toluene were added dropwise 4-fluorobenzoyl chloride (4 mL, 37 mmol) and aluminum chloride (4.9 g, 37 mmol), while the temperature was maintained at room temperature. Stirring was continued for 7 hours and then the solvent was poured into ice-water. The mixture was extracted with ethyl acetate and hexane (1:9). The combined organic layers were washed with water and brine, dried (Na2SO4) and concentrated. The residue was purified by flash silica gel chromatography to generate the desired product as a yellowish solid. Yield 40%. 1H NMR (500 MHz, CDCl3) δ 1.28 (d, J=6.8 Hz, 12H), 3.18 (hept, J=6.8 Hz, 2H), 5.34 (br s. 1H), 7.55 (s, 2H), 7.16 (d, d, J=8.6 Hz, 1H), 7.15 (d, J=8.6 Hz, 1H), 7.79 (d, J=8.6 Hz, 1H), 7.81 (d, J=8.6 Hz, 1H); Anal. Calcd for (C19H21FO2+H)+ and (C19H21FO2+H)+: 301 and 323. Fou...

example 2

[0062] This example illustrates the preparation of (4-(trifluoromethyl)phenyl)-(4-hydroxy-3,5-diisopropylphenyl)methanone (CT8). The title compound was prepared essentially as described in Example 1. 1H NMR (500 MHz, CDCl3) δ 1.27 (d, J=6.6 Hz, 12H), 3.18 (hept, J=6.6 Hz, 2H), 5.40 (br s. 1H), 7.58 (s, 2H), 7.74 (d, J=8.0 Hz, 2H), 7.85 (d, J=8.0 Hz, 2H); Anal. Calcd for (C20H21F3O2+H)+ and (C20H21F3O2+Na)+: 351 and 373. Found: 351 and 373.

example 3

[0063] This example illustrates the preparation of (4-hydroxy-3,5-diisopropylphenyl)-(4-nitrophenyl)methanone (CY61). The title compound was prepared essentially as described in Example 1. 1H NMR (500 MHz, CDCl3) δ 1.27 (d, J=6.9 Hz, 12H), 3.20 (hept, J=6.9 Hz, 2H), 5.73 (br s. 1H), 7.57 (s, 2H), 7.89 (d, J=8.8 Hz, 2H), 8.33 (d, J=8.8 Hz, 2H); Anal. Calcd for (C19H21NO4+H)+ and (C19H21NO4+Na)+: 328 and 350. Found: 328 and 350.

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
pressuresaaaaaaaaaa
pressuresaaaaaaaaaa
diameteraaaaaaaaaa
Login to View More

Abstract

The invention provides para substituted dialkylphenol derivatives of propofol. The invention further provides pharmaceutical compositions comprising such analogs, methods for preparing such analogs, and methods of using such analogs to induce general anesthesia, sedation, and / or hypnotic or sleep effects in a patient.

Description

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS [0001] This patent application claims the benefit of U.S. Provisional Patent Application No. 60 / 531,954, filed on Dec. 23, 2003, which is incorporated by reference herein.FIELD OF THE INVENTION [0002] The present invention relates to derivatives of propofol. More particularly, the invention relates to para-substituted dialkylphenol propofol compounds, processes for their preparation, and pharmaceutical compositions containing them. BACKGROUND OF THE INVENTION [0003] Propofol (2,6-diisopropylphenol, formula I), is a short-acting hypnotic agent, effective for induction and maintenance of anesthesia (see, e.g., Rees et al., Annu. Rep. Med. Chem., 31, 41-50 (1996), and Trapani et al., Curr. Med. Chem., 7, 249 (2000)). Propofol also is used for intravenous (iv) sedation by target-controlled infusions (see, e.g., Leitch, Br. Dent. J., 194, 443 (2003)). [0004] Induction of anesthesia with propofol is rapid, and maintenance can be achieved by ...

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(United States)
IPC IPC(8): A61K31/05A61K31/12C07C39/367C07C39/373C07C45/00C07C45/46C07C49/83C07C49/84C07C69/78C07C205/45C07C225/22C07C235/84C07C251/48C07C255/56C07C309/87C07C311/29C07C317/24C07C325/02C07D317/54C07D317/56C07D317/58
CPCA61K31/05A61K31/095C07D317/58C07D317/56C07D317/54A61K31/12A61K31/15C07C39/367C07C39/373C07C45/46C07C49/83C07C49/84C07C69/78C07C205/45C07C225/22C07C235/84C07C251/48C07C255/56C07C309/87C07C311/29C07C317/24C07C325/02A61P23/00A61P25/00A61P25/20
Inventor TAO, CHUNLINYU, CHENG ZHIDESAI, NEIL P.TRIEU, VUONG
Owner ABRAXIS BIOSCI LLC