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

Prodrugs and methods of making and using the same

A kind of technology of prodrug and compound, applied in the field of prodrug and its preparation and use

Inactive Publication Date: 2010-03-24
NEUROGESX INC
View PDF8 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although benzodiazepines The low toxicity of the class makes them a good choice for such diseases, but their potential for abuse makes physicians wary of prescribing them

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
  • Prodrugs and methods of making and using the same
  • Prodrugs and methods of making and using the same
  • Prodrugs and methods of making and using the same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0227] Embodiment 1: the synthesis of N-phosphonooxymethyl levorphanol

[0228] Preparation of di-tert-butyl chloromethyl phosphate (3). Di-tert-butyl chloromethyl phosphate was prepared according to Scheme 1 of the reaction example.

[0229]

[0230] Example reaction scheme 1

[0231] Di-tert-butyl phosphate (2). To a solution of di-tert-butyl phosphite (1) (25 g, 128 mmol) and potassium bicarbonate (7.g, 77.9 mmol) in 28 mL of water stirred in an ice bath was added 6 equal parts of permanganese over a period of 1 hour Potassium phosphate powder (34.7 g, 220 mmol). The purple mixture was stirred for an additional 45 minutes at room temperature. Thelerite (5 g) was added and the resulting mixture was stirred at 60°C. The mixture was filtered through a celite filter cake and the filter cake was washed with 3x50 mL of water. The combined filtrates were mixed with 10 g of sorite and stirred at 60°C for 30 minutes. The mixture was filtered again through celite, and the...

Embodiment 2

[0239] Example 2: Chemical Hydrolysis Studies

[0240]The aqueous solution stability of N-phosphonooxymethyl levorphanol at 37°C, pH 1.2, 6 and 8 was determined by comparing sample solutions at the specified time points indicated in the data table below. Various pH (1.2, 6 and 8) PBS solution. The solubility of N-phosphonooxymethyl levorphanol at pH 8 in PBS was found to be approximately 137 mg / mL. Levorphanol (free base) dissolves less than 1 mg / mL by sonication at 37°C. A 50 [mu]L sample was collected at the t=0 time point. The remaining solution was then divided into 5 aliquots (175 μL each) using microcentrifuge tubes labeled according to the sampling time point. The airtight, sealed vials were then incubated at 37°C in a temperature-controlled water bath. At each time point, the appropriate vial was removed from the water bath and a 50 μL sample was withdrawn for HPLC analysis. Table 1 below presents the HPLC analytical data indicating the test conditions, samplin...

Embodiment 3

[0247] Example 3: Enzymatic Hydrolysis Studies

[0248] Determination of N-phosphonooxymethyllevorphanol by HPLC by comparing the area under the peak of the sample solution at specific time points (0, 0.5, 1.25, 3, 5.5, and 23 hours) with the area under the peak of a freshly prepared sample Stability at pH 8, 37°C in the presence of alkaline phosphatase (EC 3.1.3.1; Sigma-Aldrich catalog #P7923). Alkaline phosphatase (400 units) was added to 10 mL of alkaline phosphatase stabilization buffer (APSB; Sigma-Aldrich catalog #A4955) maintained at 37°C. The pH of the solution was determined by dropping 25 μL of the solution onto a calibrated color-pH indicator strip (pH 2-9, Darmstadt, Germany) and comparing the color to the calibrated range. N-phosphonooxymethyllevorphanol (3 mg) was added to 3 mL of the above enzyme+buffer and incubated at 37°C. At each sampling time point, 200 μL aliquots were injected into labeled microcentrifuge tubes, each containing 50 μL of Alkaline Phos...

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

Prodrugs of parent drugs and methods of making and using the same are described. The prodrugs comprise an amine-containing parent drug moiety and a prodrug moiety, such as methoxyphosphonic acid or ethoxyphosphonic acid. The prodrugs may be employed in therapy for the treatment of various indications, such as pain, and in methods of decreasing the abuse potential of abuse-prone drugs and / or delaying the onset of parent drug activity and / or prolonging parent drug activity as compared to administration of a parent drug.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Application Serial No. 60 / 873,519, filed December 5, 2006. [0003] Statement Regarding Federally Sponsored Research or Development [0004] not applicable. Background of the invention [0005] Many therapeutically beneficial drugs have one or more undesired properties that limit the drug's use in therapy. For example, the administration of certain drugs is accompanied by unwanted side effects. Certain drugs have a short half-life, while others are unstable or have a limited shelf life. Still other drugs, while therapeutically effective, still have potential for abuse. [0006] Drugs prone to abuse constitute a broad drug spectrum with applications in various therapeutic areas such as pain, insomnia, narcolepsy, depression, attention deficit disorder, attention deficit hyperactivity disorder, panic anxiety disorder, anesthesia, and weight loss. Opioids, stimulants, ...

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): A61K47/48
CPCA61K47/48084A61K47/548A61P19/02A61P25/04A61P25/14A61P25/20A61P25/22A61P25/24A61P29/00A61K31/343C07D211/28C07D225/06C07D489/12
Inventor N·穆罕默德K·R·布雷
Owner NEUROGESX INC
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