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-10662179-B2
Publication Date
2020-05-26
Expiration Date
Abstract
A process for preparing a compound of formula (I): includes reacting a compound of formula (II): with a compound of formula (III):
Core Innovation
The invention relates to a process for preparing a compound of formula (I), or a salt thereof, wherein substituent variables are defined by R, R1a, R1b, R2, R3, R4, X, Y, R5, and R6. The process comprises reacting a compound of formula (II), or an activated derivative thereof, with a compound of formula (III), and alternative reacting routes use compounds of formulas (XV) and (XI) where Z is a leaving group, or compounds of formulas (XX) and (XXI).
The invention further relates to antifungal compounds of formula (I) and includes pharmaceutical composition and formulation uses. The compounds of formula (I) are defined with multiple substituent variables including hydrogen, halo, cyano, haloalkyl, haloalkoxy, alkyl, alkoxy, hydroxyalkyl, and SO2NR5R6 options, and the structural definitions support multiple related compound embodiments and salts.
The problem addressed is the treatment of mycoses, including Aspergillus spp. and Candida spp., and the reported biological relevance is stated as potent inhibition of Aspergillus fumigatus growth in vitro and inhibition of Aspergillus infections in immunosuppressed mice.
Claims Coverage
The claim set includes three independent process claims, each defining a process for preparing a compound of formula (I) (or a salt thereof) via a different reaction framework. Across the independent claims, the inventive features primarily lie in the defined reaction pairings and the narrowed substituent-variable selections introduced by dependent claims.
Reacting formula (II) with formula (III) to prepare formula (I)
A process for preparing a compound of formula (I) (or a salt thereof), comprising reacting a compound of formula (II) (or an activated derivative thereof or a salt thereof) with a compound of formula (III) (or a salt thereof), where the variables R, R1a, R1b, R2, R3, R4, X, Y, R5, and R6 are as defined for formula (I).
Reacting formula (XV) with formula (XI) using a leaving group Z
A process for preparing a compound of formula (I) (or a salt thereof), comprising reacting a compound of formula (XV) (or its salt) with a compound of formula (XI) (or its salt), where Z represents a leaving group, and where R, R1a, R1b, R2, R3, R4, X, and Y are as defined for the compound of formula (I).
Reacting formula (XX) with formula (XXI) to prepare formula (I)
A process for preparing a compound of formula (I) (or a salt thereof), comprising reacting a compound of formula (XX) (or its salt) with a compound of formula (XXI) (or its salt), where R2, R3, R4, and X are as defined for the compound of formula (I) for formula (XX), and R, R1a, and R1b are as defined for the compound of formula (I) for formula (XXI).
Overall, the claim coverage is directed to preparing compounds of formula (I) by reacting specific precursor formulas (II)+(III), (XV)+(XI) where XI includes a leaving group Z, and (XX)+(XXI). The dependent claims narrow the broad variable definitions by fixing specific selections for R, R1a, R1b, R2, R3, R4, X, Y, and Z.
Stated Advantages
Potent inhibition of Aspergillus fumigatus growth in vitro.
Inhibition of Aspergillus infections in immunosuppressed mice.
Documented Applications
Use of the antifungal compounds of formula (I) against mycoses, including Aspergillus spp. and Candida spp., with evaluation against Aspergillus fumigatus growth and Aspergillus infections.
Pharmaceutical composition and formulation uses.
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