Process for preparing a compound useful to treat mycoses
Inventors
COLLEY, Thomas Christopher • Ito, Kazuhiro • RAPEPORT, Garth • Strong, Peter • Murray, Peter John • Onions, Stuart Thomas • Sunose, Mihiro
Assignees
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Publication Number
US-11661415-B2
Publication Date
2023-05-30
Expiration Date
Abstract
A process for preparing a compound of formula (II): includes reacting a compound of formula (VIII): with a compound of formula (XIV):
Core Innovation
The patent describes an aqueous suspension formulation comprising a compound of formula (I) or a specific triazole/difluorophenyl piperazine benzamide compound identified as Example 1, optionally as a pharmaceutically acceptable salt. The document defines the compound family by variable substituent options and presents representative embodiments within that formula family.
The document characterizes the compounds in the context of mycoses, particularly invasive or airway fungal infections such as pulmonary aspergillosis caused by Aspergillus spp. It also reports biological evaluation against Aspergillus fumigatus, including azole-sensitive and azole-resistant strains, with potency, cytotoxicity, and infection-related assay readouts.
The document further describes aqueous suspension and topical administration contexts, including application to lung or nose and inhalation formulation contexts. It also reports combination effects with posaconazole and in vivo mouse efficacy in immunocompromised neutropenic A/J models with prophylactic and therapeutic intranasal dosing.
Claims Coverage
The claim coverage identifies one inventive feature centered on an aqueous suspension formulation of a compound of formula (I) with defined substituent-variable options, optionally as a pharmaceutically acceptable salt.
Aqueous suspension formulation of a compound of formula (I)
An aqueous suspension formulation comprising a compound of formula (I), wherein variable substituents are defined as specified in the claim, optionally as a pharmaceutically acceptable salt thereof.
Overall, the claim coverage centers on an aqueous suspension formulation of compound of formula (I) with specifically defined substituent options, optionally as a pharmaceutically acceptable salt.
Stated Advantages
Potent antifungal activity, including inhibition of Aspergillus fumigatus and potent inhibition of fungal infection in immunosuppressed mice.
Low systemic exposure after topical administration.
Sustained inhibition and extended DFB50 versus monotherapy with posaconazole.
Reduced inflammatory cell accumulation, body-weight loss outcomes, and survival compared with posaconazole monotherapy.
Documented Applications
Treatment or prevention of mycoses, including invasive or airway fungal infections such as pulmonary aspergillosis caused by Aspergillus spp.
Formulations for topical administration to lung or nose, including inhalation formulation contexts.
Use in combination contexts with antifungal and other partner agents, including azoles, amphotericin B, echinocandins, and inhibitors of HMG-CoA reductase.
Treatment and/or prevention of mycosis, including mycosis caused by Aspergillus spp.
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