Synthesis and hydrolytic behavior of two novel tripartate codrugs of naltrexone and 6beta-naltrexol with hydroxybupropion as potential alcohol abuse and smoking cessation agents.

Synthesis and hydrolytic behavior of two novel tripartate codrugs of naltrexone and 6beta-naltrexol with hydroxybupropion as potential alcohol abuse and smoking cessation agents. Research Abstract Details 

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Synthesis and hydrolytic behavior of two novel tripartate codrugs of naltrexone and 6beta-naltrexol with hydroxybupropion as potential alcohol abuse and smoking cessation agents. Abstract Text:

Mohamed O Hamad,Paul K Kiptoo,Audra L Stinchcomb,Peter A Crooks,

A codrug approach for simultaneous treatment of alcohol abuse and tobacco dependence is considered as very desirable because of substantial evidence that smoking is increased significantly during drinking, and that smoking is regarded as a behavioral 'cue' for the urge to consume alcohol. The purpose of this study was to design and synthesize codrugs for simultaneous treatment of alcohol abuse and tobacco dependence. Two novel tripartate codrugs of naltrexone (NTX) and naltrexol (NTXOL) covalently linked to hydroxybupropion (BUPOH) were synthesized (25 and 26, respectively), and their hydrolytic cleavage to the parent drugs was determined. These codrugs were generally less crystalline when compared to NTX, or NTXOL, as indicated by their lower melting points, and were expected to be more lipid-soluble. Also, the calculated clogP values were found to be higher for the codrugs compared to those for NTX and NTXOL. The studies on the hydrolysis of the codrugs provided good evidence that they could be efficiently converted to the parent drugs in buffer at physiological pH. Thus, these codrugs are likely to be cleaved enzymatically in vivo to generate the parent drugs, and are considered to be potential candidates for simultaneous treatment of alcohol abuse and tobacco dependence.

Synthesis and hydrolytic behavior of two novel tripartate codrugs of naltrexone and 6beta-naltrexol with hydroxybupropion as potential alcohol abuse and smoking cessation agents. Publishing Authors By Initials

MO Hamad,PK Kiptoo,AL Stinchcomb,PA Crooks,

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Synthesis and hydrolytic behavior of two novel tripartate codrugs of naltrexone and 6beta-naltrexol with hydroxybupropion as potential alcohol abuse and smoking cessation agents. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Bioorganic & medicinal chemistry

VOLUME: 14

Page Numbers: 7051-61

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ISSN: 0968-0896

DAY: 23

MONTH: 06

YEAR: 2006

Synthesis and hydrolytic behavior of two novel tripartate codrugs of naltrexone and 6beta-naltrexol with hydroxybupropion as potential alcohol abuse and smoking cessation agents. Information

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LANGUAGE: eng

NlmUniqueID: 9413298

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Grant and Affiliation Information for Synthesis and hydrolytic behavior of two novel tripartate codrugs of naltrexone and 6beta-naltrexol with hydroxybupropion as potential alcohol abuse and smoking cessation agents.

AFFILIATION: College of Pharmacy, Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536-0082, USA.

Country: England

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MEDLINETA: Bioorg Med Chem

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