Meta tyrosine derivatives as rho-kinase inhibitors
Inventors
Accetta, Alessandro • RANCATI, Fabio • Edwards, Christine • Bhalay, Gurdip • TISSELLI, Patrizia
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11725007-B2
Publication Date
2023-08-15
Expiration Date
Abstract
The invention relates to compounds of formula (I) inhibiting Rho Kinase that are meta tyrosine derivatives, processes for preparing such compounds, pharmaceutical compositions containing them and therapeutic use thereof. Particularly the compounds of the invention may be useful in the treatment of many disorders associated with ROCK enzymes mechanisms, such as pulmonary diseases including asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH).
Core Innovation
The invention relates to a compound of formula (I) having variable integers n, q, and m that are zero or an integer from 1 to 2. The compound includes substituent group definitions for R1, and for R2 and R3, with R2 and R3 either selected from specified classes or alternatively taken together with the nitrogen atom they are linked to to form a mono-cyclic saturated or partially saturated heterocyclic radical. The invention also covers pharmaceutically acceptable salts and solvates of the compound.
The partial content describes the preparation of substituted pyrrolo[2,3-b]pyridine oxyphenyl acyl/amide derivatives that match the claimed core scaffold. It includes formation of a substituted intermediate via coupling of an intermediate with 1-methylpiperazine, followed by deprotection/workup to obtain Example 1, and characterization using LCMS and 1H NMR. It further describes the synthesis of multiple analogs by substituting different amines and providing characterization data.
The partial content also describes an additional example prepared from protected intermediates through acrylate formation, construction of a nitrobutanoate, reduction, Boc protection, ester hydrolysis, and then coupling with 2-(pyridin-4-yl)ethylamine. The resulting example corresponds to a specific butanamide structure containing a 3-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl oxy phenyl motif and an N-(2-(pyridin-4-yl)ethyl) butanamide portion, and includes LCMS and 1H NMR characterization.
Claims Coverage
The document contains one independent compound claim and additional dependent claims that refine compound parameters and include pharmaceutically acceptable salts and solvates.
Compound of formula (I) with variable integers n, q, and m
A compound of formula (I) wherein n, q and m are zero or an integer from 1 to 2.
Defined substituent selection for R1, R2 and R3
R1 is selected from the group consisting of H, halogen, CN, and (C1-C6) alkyl, and R2 and R3, the same or different, are selected from the group consisting of H, (C1-C6) alkyl, (C1-C6) haloalkyl, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, (C1-C6) alkoxy (C1-C6) alkyl, and heteroaryl(C1-C6)alkyl.
Heterocyclic radical formed by R2 and R3 linked to nitrogen
Alternatively, R2 and R3, taken together with the nitrogen atom they are linked to, form a mono-cyclic saturated or partially saturated heterocyclic radical, wherein at least one further ring carbon atom is optionally replaced by N, and the heterocyclic radical is optionally further substituted with one or more (C1-C6) alkyl groups.
Pharmaceutically acceptable salts and solvates
The compound of formula (I) is provided together with pharmaceutically acceptable salts and solvates thereof.
The claim coverage focuses on a compound framework defined by formula (I), with substituent classes for R1 and for R2/R3 or an alternative mono-cyclic heterocyclic radical option, and explicitly includes pharmaceutically acceptable salts and solvates.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
Interested in licensing this patent?