Hepatitis B capsid assembly modulators
Inventors
Burns, Christopher J. • COBURN, Glen • Liu, Bin • Yao, Jiangchao • BENETATOS, Christopher • Boyd, Steven A. • Condon, Stephen M. • Haimowitz, Thomas
Assignees
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Publication Number
US-11566001-B2
Publication Date
2023-01-31
Expiration Date
Abstract
Described herein are hepatitis B capsid assembly modulators and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for the treatment of hepatitis B.
Core Innovation
The invention relates to compounds of Formula (Ia), or pharmaceutically acceptable salts, solvates, or stereoisomers thereof. The compounds include a substituted pyrrole-carboxamide scaffold with Ring A as aryl and variable substituents R11, R12, R13, R16, and R17, with R17 as cycloalkyl optionally substituted with one, two, or three R7 groups and further R7, R7a, Ra, Rb, and Rc definitions. The disclosed chemical space includes pyrrole-3-carboxamide, tetrahydroindolizine-1-carboxamide, pyrrolizine-7-carboxamide, and related heteroaryl carboxamide scaffolds.
The examples describe specific small-molecule embodiments within the Formula (Ia) space, including N-aryl or heteroaryl groups, stereoisomeric variants, and compounds with cycloalkyl or heterocyclic amino side chains. The exemplified structures include fluoro-, chloro-, methyl-, difluoro-, trifluoromethyl-, and other defined substituent patterns, together with bicyclic, azabicyclic, morpholine, piperidine, piperazine, oxadiazole, thiazole, and other heterocycle-containing variants. The document presents these compounds as concrete members of the defined Formula (Ia) structural framework.
The disclosure also identifies hepatitis B as a therapeutic context for the Formula (Ia) compounds. In the provided material, the compounds are described in relation to hepatitis B capsid assembly modulation and to methods of treating hepatitis B by administering the claimed compounds to a subject. Pharmaceutical composition coverage is also included together with pharmaceutically acceptable excipients.
Claims Coverage
The consolidated claim set centers on one broad independent compound claim to Formula (Ia) and dependent claims that narrow the substituent scope, together with composition and hepatitis B method claims. In total, the independent and dependent coverage identifies five inventive feature groups: the Formula (Ia) scaffold, a phenyl/fluorine subset, R13 restricted to halogen, R16 restricted to hydrogen, and the composition and treatment claims.
Formula (Ia) compound scaffold
A compound of Formula (Ia), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein Ring A is aryl; each R11 is independently halogen; n is 2 or 3; R12 is hydrogen; R13 is hydrogen, halogen, or C1-C6 alkyl; R16 is hydrogen or C1-C6 alkyl; and R17 is cycloalkyl optionally substituted with one, two, or three R7 groups, with R7, R7a, Ra, Rb, and Rc defined by the recited substituent sets.
Ring A phenyl and R11 fluorine subset
A compound of claim 1, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein Ring A is phenyl, n is 2 or 3, and each R11 is independently fluorine.
R13 halogen restriction
A compound of claim 1, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R13 is halogen.
R16 hydrogen restriction
A compound of claim 1, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R16 is hydrogen.
Pharmaceutical composition with pharmaceutically acceptable excipient
A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, together with a pharmaceutically acceptable excipient.
Method for treating hepatitis B by administering the compound
A method for treating hepatitis B by administering a compound of claim 1, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, to a subject.
Overall, the claims cover a broad Formula (Ia) compound family with defined aryl and cycloalkyl-linked substituent constraints, and narrower subsets fixing Ring A as phenyl with fluorinated R11, R13 as halogen, and R16 as hydrogen. The coverage further includes a pharmaceutical composition with an excipient and a method of treating hepatitis B by administering the claimed compound to a subject.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating hepatitis B by administering a compound of claim 1, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, to a subject.
Pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, together with a pharmaceutically acceptable excipient.
Hepatitis B capsid assembly modulation.
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