Important Compound Classes
Title
Pyrazo-tetraisoquinoline Derivaties as Dopamine D1 Receptor Positive Modulators
Patent Application Number
WO 2019204418, A1
Publication Date
October 24, 2019
Priority Application
US 2018-62660622
Priority Date
April 20, 2018
Inventors
Coates, D. A.; Hao, J.; Hilliard, D. W.
Assignee Company
Eli Lilly and Company, USA
Disease Area
Parkinson’s disease, schizophrenia, ADHD, or Alzheimer’s disease.
Biological Target
Dopamine D1 Receptor
Key Structures
Summary
The present application claims (phenyl)-(pyrazol)-3,4-dihydroisoquinolin-2(lH)-yl)ethan-l-one derivatives as selective positive allosteric modulators (PAMs) of the dopamine D1 receptor. This family of compounds is potentially useful in improving motor symptoms in Parkinson’s disease, in treating certain symptoms of Alzheimer’s disease such as cognitive impairment (e.g., MCI), and in treating certain symptoms of ADHD.
Biological Assay
The Human Dl Receptor PAM Assay was performed in HEK293 cells that stably express the human Dl receptor, and the cAMP production was quantified using HTRF detection. The absolute EC50 and % Top are shown in the following table.
Biological Data
Notes: Compound 1 and compound 8 were shown to have in vivo efficacy in a basal locomotor activity in Male human Dl receptor knock-in mice. Fifteen (15) examples are provided. Pharmacokinetic data and physical state studies are described for a few compounds.
The author declares no competing financial interest.