Heteroaryl compounds and their use as therapeutic drugs
Inventors
Kim, Myeong-Seop • KIM, Sumin • Kim, Jin Kwan • Kim, Hadong • RYU, Ki Moon • Park, Seong Jin • Park, Taesun • SHEEN, Joon-Ho • Yoon, Taeyoung • JANG, Mi Yeon
Assignees
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Publication Number
US-10125118-B2
Publication Date
2018-11-13
Expiration Date
Abstract
The present invention provides heterocyclic compounds, the stereoisomer thereof, the enantiomer thereof, or the pharmaceutically acceptable salt, which are capable of modulating the activity of Mer receptor tyrosine kinase (MERTK). This invention also provides pharmaceutical compositions thereof, methods to prepare the said compounds, and the use of such compounds as a medicament.The present invention is directed to MERTK inhibitory compounds with marked potency, thereby having an outstanding potential for a pharmaceutical intervention of cancer and any other diseases related to MERTK dysregulation.
Core Innovation
The invention relates to heterocyclic compounds represented by Formula Ia and Formula Ib, including stereoisomers, enantiomers, and pharmaceutically acceptable salts. The compounds are defined by extensive structural variables, including X, Y, W, Z, V1, V2, X1 to X5, R3, R6, R8, R9, R10, R11, R13, R13′, R14, R15, R16, R17, R18 to R21, and linker group L, with optional ring-forming combinations and substitution patterns.
The disclosure also enumerates specific nicotinamide-based examples, including compounds bearing a 1-methyl-1H-pyrazol-4-yl group and stereodefined cyclopentyl or related frameworks. Representative examples include benzyloxy-substituted and other substituted aromatic or heteroaromatic variants, together with stereochemical designations such as (1S,2S), (1R,2R), trans, cis, (3S,4S), and related derivatives.
The compounds are characterized in the examples by analytical data including 1H NMR, ESI-MS, LC-MS, and LC/ESI MS, with reported m/z [M+H] values. The disclosure further ties the heterocyclic compounds to Mer kinase inhibition and to pharmaceutical composition language with pharmaceutically acceptable carriers.
Claims Coverage
The consolidated claim coverage includes broad Formula Ia and Formula Ib heterocyclic compound claims, selected nicotinamide examples, and related pharmaceutical composition and Mer kinase-linked use claims. Across these independent claims, the inventive features include defined heterocyclic structures, stereoisomers, enantiomers, and pharmaceutically acceptable salts, together with composition and prevention or treatment language linked to Mer kinase inhibition; overall, the record supports five main inventive feature themes.
Heterocyclic compounds of Formula Ia
A heterocyclic compound represented by Formula Ia, a stereoisomer thereof, an enantiomer thereof, or a pharmaceutically acceptable salt thereof, with defined options for X, Y, W, Z, substituents R3, R6, R8, R9, R10, R11, R15, R16, R17, and R18 to R21, and optional ring-combination rules.
Heterocyclic compounds of Formula Ib
A heterocyclic compound represented by Formula Ib, a stereoisomer thereof, an enantiomer thereof, or a pharmaceutically acceptable salt thereof, with defined options for X, W, V1, V2, X1 to X5, and substituents R3, R8, R9, R10, R11, R13, R13′, R14, R15, R16, R17, and L, including ring-formation rules.
Selected nicotinamide examples
A heterocyclic compound, a stereoisomer thereof, an enantiomer thereof, or a pharmaceutically acceptable salt thereof, wherein the heterocyclic compound is any one of the listed Example compounds, including nicotinamide-based structures.
Pharmaceutical composition with pharmaceutically acceptable carrier
A pharmaceutical composition comprising a heterocyclic compound or specified heterocyclic structure, together with a pharmaceutically acceptable carrier.
Mer kinase-inhibiting prevention or treatment
A pharmaceutical composition including a Mer kinase-inhibiting heterocyclic compound in an amount effective for preventing or treating a disease influenced by Mer kinase inhibition.
Overall, the claims cover broad heterocyclic nicotinamide-related compound classes defined by Formula Ia and Formula Ib, selected examples, and pharmaceutical composition/use claims tied to Mer kinase inhibition.
Stated Advantages
Inhibition of Mer kinase.
Prevention or treatment of a disease influenced by Mer kinase inhibition.
Provides Mer activity for cancer prevention and/or treatment.
Documented Applications
A pharmaceutical composition including a Mer kinase-inhibiting heterocyclic compound for preventing or treating a disease influenced by Mer kinase inhibition.
Preventing or treating cancer.
Preventing or treating immune-related diseases including infection and sepsis.
Analytical characterization of Mer-kinase-inhibiting heterocyclic nicotinamide derivatives using MS, 1H NMR, LC-MS, LC/ESI MS, and reported m/z values.
Compound family exemplification through named examples and intermediates, including synthetic scheme references and preparation of specific examples.
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