BIA 10-2474

Ligand id: 9001

Name: BIA 10-2474

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 4
Hydrogen bond donors 0
Rotatable bonds 4
Topological polar surface area 65.07
Molecular weight 300.16
XLogP 1.72
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

Classification
Compound class Synthetic organic
IUPAC Name
N-cyclohexyl-N-methyl-4-(1-oxidopyridin-1-ium-3-yl)imidazole-1-carboxamide
Synonyms
BIA-10-2474 | BIA-102474 | example 362 [WO2010074588] [2]
Database Links
GtoPdb PubChem SID 310264779
PubChem CID 46831476
Search Google for chemical match using the InChIKey DOWVMJFBDGWVML-UHFFFAOYSA-N
Search Google for chemicals with the same backbone DOWVMJFBDGWVML
Search UniChem for chemical match using the InChIKey DOWVMJFBDGWVML-UHFFFAOYSA-N
Search UniChem for chemicals with the same backbone DOWVMJFBDGWVML
Wikipedia BIA 10-2474
Comments
BIA 10-2474 was beleived to be reversible inhibitor of fatty acid amide hydrolase (FAAH). It was the heart of a disaterous clinical trial in France which left one participant dead and several others with possibly permanent brain damage. The compound is claimed in patent WO2010074588 [2].
The structure of BIA 10-2474 was disclosed in a clinical trial protocol with EudraCT No: 2015-001799-24.
Pharmacologic inhibition of FAAH is being investigated in the search for novel analgesic drugs [3-5].
More information surrounding this compound and its unfortunate clinical trial outcome is available in two blogposts by our curator Christopher Southan (The unfortunate case of BIA-10-2474 and Molecular details related to BIA 10-2474).

Subsequent analysis of BIA 10-2474's pharmacology is reported by van Esbroeck et al. (2017) [6]. This anaylsis suggests that BIA 10-2474's interaction with FAAH is in fact irreversible. Using activity-based protein profiling (ABPP), this same study reveals that BIA 10-2474 (and its metabolite BIA 10-2639) engages numerous human off-targets including FAAH2 and several lipid serine hydrolases, such as ABHD6, ABHD11, LIPE, and PNPLA6, and xenobiotic drug-metabolizing enzymes CES1, CES2, and CES3, with greater inhibition of ABHD6 and CES2 compared to PNPLA6. The authors postulate that BIA 10-2474 may act to dramatically alter brain lipid metabolism and that this action may have contributed to the compound's neurotoxicity. In the same assays, this action was not replicated by the clinically tested FAAH inhibitor PF-04457845.