Important Compound Classes
Title
Tetrazole Derivatives as TRPA1 Inhibitors
Patent Publication Number
WO 2022/079092 A1
Publication Date
April 21, 2022
Priority Application
EP 20201708.3
Priority Date
October 14, 2020
Inventors
Fleck, M. T.; Binder, F. P. C.; Willwacher, J.
Assignee Company
Boehringer Ingelheim International GmbH, Germany
Disease Area
Idiopathic lung disease or cough
Biological Target
TRPA1
Summary
Transient receptor potential channels (TRP channels) are a group of voltage-gated ion channels located mostly on the plasma membrane of numerous mammalian cell types. There are approximately 30 TRP channels sorted into several groups: TRPA, TRPC, TRPM, TRPML, TRPN, TRPP, and TRPV. Transient receptor potential ankyrin 1 (TRPA1) is best known as a sensor for environmental irritants giving rise to somatosensory modalities such as pain, cold, and itch.
TRPA1 is activated by a number of reactive, electrophilic stimuli and non-reactive compounds implicated in cough associated with asthma, chronic pulmonary obstructive disease (COPD), idiopathic pulmonary fibrosis (IPF), post-viral cough, and chronic idiopathic cough. TRPA1 antagonists are effective in studies of atopic dermatitis, contact dermatitis, and psoriasis-associated itch.
The present application describes a series of novel tetrazole derivatives as TRPA1 inhibitors for the treatment of idiopathic lung disease or cough. Further, the application discloses compounds, their preparation, use, and pharmaceutical composition, and treatment.
Definitions
A = phenyl, thienophenyl, benzothiophenyl, and benzofuranyl, unsubstituted or substituted with one or more member of the group R3 selected from CN, halogen, C1-4 alkyl, O-C1-4 alkyl, C1-4 fluoroalkyl, O-C1-4 fluoroalkyl, C3-4 cycloalkyl, O-C3-4 cycloalkyl, C3-4 cyclofluoroalkyl, and O-C3-4 cyclofluoroalkyl;
R1 = H, CH3, or CONH2; and R2 = CH3 or CONH2.
Key Structures
Biological Assay
The in vitro TRPA1 cell activity assay was performed. The compounds described in this application were tested for their ability to inhibit TRPA1. The TRPA1 IC50 (nM) are shown in the table below.
Biological Data
The following table shows representative compounds tested for TRPA1
inhibition and the biological data obtained from testing
representative examples.
Claims
Total claims: 13
Compound claims: 11
Salt claims: 1
Pharmaceutical composition claims: 1
The author declares no competing financial interest.
References
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