Compounds
Inventors
PORRAS DE FRANCISCO, Esther • Remuiñan-Blanco, Modesto Jesús • BOUROTTE, Marilyne • Deprez, Benoit • DEQUIREZ, Geoffroy • Willand, Nicolas
Assignees
Bioversys AG • GlaxoSmithKline Intellectual Property Development Ltd
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Publication Number
US-11253499-B2
Publication Date
2022-02-22
Expiration Date
Abstract
The invention relates to compounds of Formula (I) and their use in therapy, for example in the treatment of mycobacterial infections or in the treatment of diseases caused by Mycobacterium, such as tuberculosis.
Core Innovation
The disclosure is directed to compounds of Formula (I) and pharmaceutically acceptable salts thereof, with n, R1, and R2 constrained as defined. The compounds are presented with substituent patterns in which phenyl and pyridyl groups are optionally substituted by chloro, fluoro, cyano, C1-3 alkyl optionally substituted by one or more fluoro, or C1-3 alkoxy optionally substituted by one or more fluoro, and cycloalkyl, piperidin-1-yl, and tetrahydropyranyl groups are optionally substituted by one or two fluoro.
The subject matter further characterizes multiple specific intermediates and compound examples based on azetidine-1-carboxylate derivatives and fluorinated azetidine-containing compounds. Representative structures include tert-butyl-protected azetidine intermediates, aryl, heteroaryl, cycloalkyl, and tetrahydropyranyl substituents, and fluorophenyl, difluorophenyl, trifluoromethyl-substituted phenyl, fluoromethoxyphenyl, chloro-substituted phenyl, pyridyl variants, and cyclopropyl-, cyclopentyl-, and cyclohexylazetidine motifs.
The disclosure also describes pharmaceutical compositions and medicaments containing the compounds, and supports preparation of compounds within the defined Formula (I) scaffold by providing characterized intermediate structures and example data. The examples and claim framework together present fluorinated scaffold compounds and related azetidine-containing intermediates and salts.
Claims Coverage
The consolidated claim coverage centers on one structurally defined Formula (I) compound claim and additional claims directed to treatment of mycobacterial infection in humans and combination therapy. The compound claim focuses on the variable positions n, R1, and R2 and their tightly limited substituent sets.
A compound of Formula (I) with restricted n, R1, and R2 substituents
A compound of Formula (I) or a pharmaceutically acceptable salt thereof, where n is 1 or 2; R1 is hydrogen, fluoro, methyl or methoxy; and R2 is phenyl, pyridyl, C3-6 cycloalkyl, piperidin-1-yl or tetrahydropyranyl, with phenyl and pyridyl optionally substituted by one to three substituents independently selected from chloro, fluoro, cyano, C1-3 alkyl optionally substituted by one or more fluoro, or C1-3 alkoxy optionally substituted by one or more fluoro, and cycloalkyl, piperidin-1-yl and tetrahydropyranyl optionally substituted by one or two fluoro.
Treating a mycobacterial infection in a human
A method to treat a mycobacterial infection in a human by administering a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt thereof, as defined in Formula (I).
Combination therapy with specified anti-tuberculosis agents
A combination therapy in which the anti-tuberculosis agent is selected from a specified list of anti-tuberculosis drugs or combinations, including beta-lactams and beta-lactam combinations.
Across the provided claims, coverage is centered on a Formula (I) scaffold defined by n, R1, and R2, with optional substitution rules for phenyl, pyridyl, cycloalkyl, piperidin-1-yl, and tetrahydropyranyl. The claim set also includes treatment of mycobacterial infection in humans and combination therapy using specified anti-tuberculosis agents.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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