Ligand id: 9610

Name: CBS-3595

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 85.11
Molecular weight 356.11
XLogP 3.92
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

No information available.
Summary of Clinical Use
Dose-limiting adverse events associated with inhibition of PDE-4 (nausea, vomiting and malaise, 1−2 h postdose) experienced by four first-in-human test subjects led to discontinuation of the clinical study of CBS-3595. This was determined to be due to high levels of active metabolite CBS-3728 (PubChem CID 11012474) in humans (less of this metabolite was measured in preclinical monkey studies) and this metabolite appeared to be selective for the PDE4D3 isoform, which is considered to be responsible for the nausea/vomiting side effects of PDE4 inhibitors. Therefore, isoform selectivity is an essential consideration for the development of future clinical candidates.