Steroids having increased water solubility and resistance against metabolism, and methods for their production
Inventors
Bäckström, Torbjörn • Ragagnin, Gianna
Assignees
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Publication Number
US-8853190-B2
Publication Date
2014-10-07
Expiration Date
Abstract
Steroid compounds having increased resistance against metabolism and increased water solubility are disclosed, together with methods for their production. These substances are suitable for the manufacture of pharmaceuticals for the treatment of steroid related or steroid induced CNS disorders and for use in methods of prevention, alleviation or treatment of such disorders.
Core Innovation
The described subject matter is a steroidal compound defined as 3β-fluor, 5α-pregnan-20-one, or a pharmaceutically acceptable salt thereof, presented as steroid therapeutics for use in the context of central nervous system (CNS) disorder treatment by targeting the GABAA receptor–chloride ionophore complex (GABAA–R). The disclosure also includes pharmaceutical compositions containing a pharmaceutically effective amount of the compound or its salt with a pharmaceutically acceptable carrier. The subject matter addresses prior problems associated with metabolism and aqueous solubility.
The steroid therapeutics are described using steroid scaffolds and derivatives, including pregnane/pregnene androstane/androstene derivatives and related stereoisomers, with general formulae having variable substituents (R1–R12). The disclosure emphasizes structural design themes that protect the 3-position and modify the 20-position, including introduction of a double bond in the steroid core and replacement of the 20-keto with an oxime. The 3-position protection is described using a tertiary alcohol moiety and related substituents.
The disclosure further includes 3β-fluoro, 3α/β-ethynyl, and Δ4-pregnen-20-one oxime analogs, together with comparative mention of oxime versus keto at C20. Pharmaceutically acceptable salts, prodrugs (esters/ethers), solvates, and optical isomers are included within the scope of the steroid therapeutics, and representative compound structures are presented as embodiments of the formula I and formula II scaffolds.
Claims Coverage
The consolidated claim coverage includes one independent claim directed to a specific steroid compound, with dependent claim content adding pharmaceutical composition limitations. In total, two inventive features are identified at the independent and dependent-claim level.
3β-fluoro, 5α-pregnan-20-one steroid compound and pharmaceutically acceptable salt
A compound defined as 3β-fluoro, 5α-pregnan-20-one, or a pharmaceutically acceptable salt thereof.
Pharmaceutical composition with effective amount and carrier
A pharmaceutical composition comprising a pharmaceutically effective amount of the compound of 3β-fluoro, 5α-pregnan-20-one or a salt thereof together with a pharmaceutically acceptable carrier.
The claim coverage is centered on the specific fluorinated steroid compound and its pharmaceutically acceptable salt, with a dependent claim directed to a pharmaceutical composition containing a pharmaceutically effective amount and a pharmaceutically acceptable carrier.
Stated Advantages
Improved metabolic resistance.
Increased water solubility versus saturated or keto/hydroxy references.
Feasibility of oral administration in the context of CNS disorder treatment.
Higher hydrophilicity indicated by HPLC retention-time comparisons versus the saturated or keto/hydroxy references.
Treatment of CNS disorders via targeting the GABAA receptor–chloride ionophore complex (GABAA–R).
Documented Applications
Use of the disclosed steroid therapeutics for treating central nervous system (CNS) disorders by targeting the GABAA receptor–chloride ionophore complex (GABAA–R).
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