Fatty alcohol drug conjugates

Abstract

The invention provides conjugates of fatty alcohols and pharmaceutical agents useful in treating cancer, viruses, psychiatric disorders. Compositions, pharmaceutical preparations, and methods of preparation of the fatty alcohols-pharmaceutical agent conjugates are provided.

Description

RELATED APPLICATIONS [0001] This application is a divisional application of U.S. non-provisional application Ser. No. 10 / 107,537, filed Mar. 25, 2002, currently pending, which claims benefit under 35 U.S.C. §119(e) of U.S. provisional Patent Application No. 60 / 278,457, filed Mar. 23, 2001, the entire contents of both of which are herein incorporated by reference.FIELD OF THE INVENTION [0002] The invention relates to conjugates of fatty alcohols and pharmaceutical agents such as anticancer, antiviral, and antipsychotic agents useful, for example, in treating cancer, viruses, and psychiatric disorders, and compositions and formulations thereof. Methods for making and using the conjugates also are provided. BACKGROUND OF THE INVENTION [0003] Improving drug selectivity for target tissue is an established goal in the medical arts. In general, it is desirable to deliver a drug selectively to its target, so that dosage and, consequently, side effects can be reduced. This is particularly th...

AI Technical Summary

Benefits of technology

[0009] The invention relates to the surprising discovery that fatty alcohols can be conjugated to pharmaceutical agents for treatment of a variety of disorders, including but not limited to cancer, viral infections, and psychiatric diseases. The benefits of these pharmaceutical-fatty alcohol conjugates include one or more of the following: targeting of the drug to the tissue of interest; favorably affecting the volume of distribution of the drug in the tissue of interest; reducing toxicity of the drug; reducing side effects of the drug; reducing clearance of the drug; reducing the necessary volume and / or frequency of administration of the drug, or increasing the amount of drug that a subject can tolerate by favorably affecting volume of distribution, tissue distribution, and / or release kinetics of active drug from an inactive conjugate in certain embodiments. Another surprising aspect of the fatty alcohol-pharmaceutical agent conjugates is that once the fatty alcohols are separated from conjugation to the pharmaceutical agents in vivo, the fatty alcohols can be readily converted into naturally occurring fatty acids.

[0010] Any and all of these aforementioned characteristics of the fatty alcohol-pharmaceutical agent conjugates may benefit subjects in need of treatment for diseases such as cancer, psychiatric disorders, and viral diseases and may allow altered dosages of drugs to be administered less frequently, with better results and fewer side effects.

[0123] The conjugated anticancer compounds described herein are less toxic and more effective than the corresponding unconjugated anticancer compounds. Therefore the fatty alcohol-anticancer compound conjugates can be administered in amounts which are equally toxic but more effective, or in doses which are equally effective and less toxic than the corresponding unconjugated anticancer compounds. In general, conjugation of fatty alcohol to anticancer compounds permits an increase in the maximum tolerated dose relative to unconjugated anticancer compounds.

Problems solved by technology

This is particularly the case for toxic agents such as anticancer agents because achieving therapeutic doses effective for treating the cancer is often limited by the toxic side effects of the anticancer agent on normal, healthy tissue.

This increase in potency, however, was not observed when the same lipid derivatives of adenosine receptor antagonists were used, and generalizations thus were not made possible by those studies.

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