Derivatives of quinoline as inhibitors of DYRK1A and/or DYRK1B kinases
Inventors
Dreas, Agnieszka • Fabritius, Charles-Henry • Dzienia, Andrzej • Buda, Anna • Galezowski, Michal • Kachkovskyi, Georgiy • Kulesza, Urszula • Kucwaj-Brysz, Katarzyna • Szamborska-Gbur, Agnieszka • Czardybon, Wojciech • Vilenchik, Maria • Frid, Michael • Kuznetsova, Alexandra
Assignees
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Publication Number
US-10577365-B2
Publication Date
2020-03-03
Expiration Date
Abstract
The present invention relates to the compound of formula (I) and salts, stereoisomers, tautomers or N-oxides thereof. The present invention is further concerned with the use of such a compound or salt, stereoisomer, tautomer or N-oxide thereof as medicament and a pharmaceutical composition comprising said compound.
Core Innovation
The invention relates to compounds of formula (I), or salts, stereoisomers, tautomers or N-oxides thereof, defined by multiple position-dependent substituents selected from explicitly stated groups. The variables include R1, R2, R3, R4, R5, R6, R6a, R6b, R7, R8, R9, R10, R11, R11a and R11b, with substitutable carbon atoms and heteroatoms independently unsubstituted or substituted with one or more listed substituents.
The scope includes heterocyclic, heterobicyclic, carbocyclic and carbobicyclic ring systems containing O, N or S, with N- and/or S-atoms independently oxidized or non-oxidized, and ring sizes of 3- to 9-membered and 6- to 14-membered. The structural scope includes carbonyl, sulfonyl, sulfinyl, oxy and amino-containing patterns, together with carbon-based substituents such as H, halogen, CN, NO2, C1-C6-alkyl, C1-C6-haloalkyl, C2-C6-alkenyl and C2-C6-alkynyl.
The disclosure also describes a pharmaceutical-relevant fused heteroaromatic scaffold including pyrrolo[2,3-b]pyridine, quinoline and pyridine substitution patterns, with named example compounds, hydrochloride salts, and stereochemical and tautomeric forms. The examples further include substituted quinoline derivatives and pyrrolo[2,3-b]pyridine derivatives, as well as reported synthetic examples and intermediates within the described chemical series.
Claims Coverage
The consolidated claim coverage centers on one independent compound claim for formula (I) and dependent claims that refine substituent choices, ring-size constraints and formulation coverage. Across the provided items, the independent claim defines a broad genus of compounds with extensive substituent selection and heterocyclic/heterobicyclic ring systems containing O, N and/or S with optional oxidation states; one dependent claim also covers a pharmaceutical composition. The inventive features below merge overlapping claim language from the inputs.
Compound of formula (I) with defined substituent scope
A compound of formula (I), or a salt, stereoisomer, tautomer or N-oxide thereof, wherein R1 and R3 are independently selected from explicitly listed groups, R2 and R4 are independently selected from explicitly listed groups, R5, R6, R6a and R6b are independently selected from explicitly listed groups, and the compound includes cyclic and bicyclic moieties with heteroatoms selected from O, N or S and optionally oxidized or non-oxidized N- and/or S-atoms.
Narrowed R2 substituent scope
The compound of claim 1, wherein R2 is selected from H, halogen, CN, NO2, C1-C2-alkyl, C1-C2-alkenyl, C1-C2-alkoxy and C1-C2-haloalkoxy, or the broader R2 list recited in the other claim texts.
Constrained R4 and ring-size limitation
The compound of claim 1 is defined by a specific substituent R4 and by containing a specified 5- to 6-membered saturated, partially unsaturated or fully unsaturated carbocyclic or heterocyclic moiety, with N- and/or S-atoms optionally oxidized or non-oxidized.
Defined R5, R6, R6a and R6b with 5- to 6-membered ring attachment
The compound of claim 1 is defined by specific independent choices for R5, R6, R6a and R6b and by attachment to a 5- to 6-membered saturated, partially unsaturated or fully unsaturated carbocyclic or heterocyclic ring containing O, N and/or S, together with independently chosen substituents on substitutable carbon atoms and heteroatoms.
Enumerated heterocyclic derivative structures
A compound selected from a defined group of specific named heterocyclic and substituted quinoline/pyrrolopyridine derivatives, including hydrochloride salts.
Pharmaceutical composition
A pharmaceutical composition containing a pharmaceutically effective amount of the compound of claim 1, optionally together with a pharmaceutically acceptable carrier, diluent or excipient.
The claim coverage is centered on the formula (I) compound definition with broadly and then more narrowly defined substituent and ring-system options, including 5- to 6-membered ring limitations in dependent claims. The merged claim set also includes enumerated named derivative structures and a pharmaceutical composition claim.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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