5,6-dihydro-1H-pyridin-2-one compounds
Inventors
Tran, Chinh V. • Ruebsam, Frank • Murphy, Douglas E. • Dragovich, Peter • Zhou, Yuefen • Chen, Lijian • Kucera, David
Assignees
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Publication Number
US-7939524-B2
Publication Date
2011-05-10
Expiration Date
Abstract
The invention is directed to 5,6-dihydro-1H-pyridin-2-one compounds of Formula I wherein X is N, and A is and pharmaceutical compositions containing such compounds that are useful in treating infections by hepatitis C virus.
Core Innovation
The document discloses a broad class of compounds of Formula I, wherein X is N and Ring B is a 6-membered aryl optionally substituted by 1-3 R1 moieties. The structure is defined by multiple variables, including A, R1, R2, R4-R16, Z, and n, with each variable constrained to specified structural options and optional substitution patterns, and it includes coverage of a pharmaceutically acceptable salt or stereoisomer thereof.
The disclosed scaffold family is centered on tricyclic benzo[1,2,4]thiadiazin derivatives and related aza-tricyclic and oxa-tricyclic variants, including methanesulfonamide derivatives with substituted benzyl groups such as 4-fluoro-benzyl. Representative structures include hydroxy- and oxo-substituted 3-aza-tricyclo[6.2.1.0^2,7]undec-5-en-5-yl cores, together with stereochemical forms such as rac-di-exo, rac-di-endo, and defined (1R,2S,7R,8S) configurations.
The document also describes a process for preparing 5,6-dihydro-1H-pyridin-2-one compounds. The process includes forming a camphorsulfonate compound from a tricyclic compound using (1S)-(+)-10-camphorsulfonic acid, performing reductive amination with 4-fluorobenzaldehyde to produce an ester compound, coupling the ester with an acetic acid compound, and cyclizing to yield a 5,6-dihydro-1H-pyridin-2-one compound.
Claims Coverage
The consolidated claim coverage includes three main inventive features for the compound genus and one process claim. It centers on the Formula I structural definition with constrained substituent classes, coverage of pharmaceutically acceptable salts or stereoisomers, and a defined multi-step process to prepare 5,6-dihydro-1H-pyridin-2-one compounds.
Compound of formula I with defined heteroatom X and ring B
A compound of Formula I wherein X is N and Ring B is a 6-membered aryl optionally substituted by 1-3 R1 moieties, with A and the remaining variables constrained by the defined structural options.
Substituent variables with constrained chemical classes and optional substitution
R1, R2, R4-R16, Z, n, and R7-R8 are independently limited to specified groups and optional substitution patterns, including Z as -(CR13R14)n- or O with n being 1 or 2.
Pharmaceutically acceptable salt or stereoisomer coverage
The compound of Formula I is included as a pharmaceutically acceptable salt or stereoisomer thereof.
Process for preparing 5,6-dihydro-1H-pyridin-2-one
A process comprising camphorsulfonate formation from a tricyclic compound, reductive amination with 4-fluorobenzaldehyde, coupling with an acetic acid compound, and cyclization to form a 5,6-dihydro-1H-pyridin-2-one compound.
Overall, the claims cover a broad Formula I compound class with tightly specified variable architecture and salt or stereoisomer coverage, together with a defined synthetic process leading to a 5,6-dihydro-1H-pyridin-2-one scaffold.
Stated Advantages
Treating hepatitis C virus (HCV) infection in a mammal.
Preventing hepatitis C virus (HCV) infection.
Inhibiting HCV NS5B polymerase.
Documented Applications
Use of the Formula I compounds for treating hepatitis C virus (HCV) infection in a mammal in need thereof.
Use of the Formula I compounds for preventing hepatitis C virus (HCV) infection.
Use in mammalian treatment contexts described as a medicament, including combinations with excipients and possible co-administration with additional antiviral agent(s) and immunomodulatory agent(s).
Formulation as a pharmaceutically acceptable composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.
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