Antifungal compound process
Inventors
Hoekstra, William J. • Yates, Christopher M. • Behnke, Mark • Alimardanov, Asaf • David, Scott A. • Fry, Douglas Franklin
Assignees
Mycovia Pharmaceuticals Inc • US Department of Health and Human Services
Publication Number
US-10421741-B2
Publication Date
2019-09-24
Expiration Date
2035-03-19
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Abstract
The present invention relates to a process for preparing compound 1 that is useful as an antifungal agent. In particular, the invention seeks to provide new methodology for preparing compound 1 and substituted derivatives thereof.
Core Innovation
The invention provides a process for preparing compound 1, useful as an antifungal agent, including substituted derivatives thereof. It offers new methodology for preparing these compounds, involving a series of synthetic steps such as epoxide opening, arylation, olefination, dihydroxylation, activation of primary alcohols, ring closure, and enantiomeric enrichment by crystallization with chiral acids.
The invention addresses the need for optimal metal-binding groups in metalloenzyme inhibitors, which balance potency and selectivity to reduce clinical toxicity stemming from off-target inhibition. Existing azole antifungal agents show indiscriminate binding leading to toxicity. Hence, developing improved methodology for efficient and selective synthesis of such therapeutic agents, including compound 1, is significant to meet unmet medical needs.
Claims Coverage
The patent includes two independent claims directed to specific compounds of formula IVb and VI* or VIa, or mixtures thereof. These claims focus on chemical structures central to the invention.
Compound of formula IVb
This feature claims a compound defined by formula IVb with specified structural characteristics.
Compound of formula VI* or VIa, or a mixture thereof
This feature claims compounds of formula VI* or VIa including mixtures, encompassing particular substituents as defined in the patent.
The claims collectively cover the novel compounds represented by formula IVb and VI* or VIa, defining their chemical structures and compositions as inventive embodiments of the invention.
Stated Advantages
The invention provides improved efficiency and selectivity in the synthesis of antifungal compounds, addressing prior issues with potency and off-target toxicity.
The methodology enables production of enantiomerically enriched compounds suitable for pharmaceutical use.
The synthetic process supports scalability from laboratory to commercial production.
Documented Applications
The compounds are useful as antifungal agents inhibiting lanosterol demethylase (CYP51) activity.
Pharmaceutical compositions comprising these compounds can be used to treat subjects suffering from metalloenzyme-related disorders or diseases.
Methods of modulating metalloenzyme activity in subjects by administering these compounds are described.
Agricultural applications include using the compounds as herbicides, pesticides, or growth regulators by treatment of plants or fields.
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