ABT-354

Clinical data
Other names	SLV-354, SLV354
Legal status
Legal status	Investigational
Identifiers
IUPAC name N-[[5-[[N-Ethyl-C-(4-ethyl-3,4-dihydropyrazol-2-yl)carbonimidoyl]sulfamoyl]thiophen-2-yl]methyl]benzamide
PubChemCID	24759217
Chemical and physical data
Formula	C20H25N5O3S2
Molar mass	447.57 g·mol−1
3D model (JSmol)	Interactive image
SMILES CCC1CN(N=C1)C(=NCC)NS(=O)(=O)C2=CC=C(S2)CNC(=O)C3=CC=CC=C3
InChI InChI=1S/C20H25N5O3S2/c1-3-15-12-23-25(14-15)20(21-4-2)24-30(27,28)18-11-10-17(29-18)13-22-19(26)16-8-6-5-7-9-16/h5-12,15H,3-4,13-14H2,1-2H3,(H,21,24)(H,22,26) Key:MGPUNPTXLIXELQ-UHFFFAOYSA-N

ABT-354 (also known asSLV-354 orSLV354) is an investigational small molecule drug developed byAbbVie, Inc. as a selective antagonist of the serotonin5-HT₆ receptor (HTR6), with intended applications in the treatment ofcognitive disorders such as mild-to-moderateAlzheimer’s disease.^[1]

ABT-354 selectively antagonizes the 5-HT₆ receptor, aG protein-coupled receptor almost exclusively expressed in thecentral nervous system (CNS), where it modulatesneurotransmitter systems includingacetylcholine,glutamate,dopamine, andnorepinephrine.^[2] Blockade of 5-HT₆ receptors has been shown in preclinical models to enhance cholinergic andglutamatergic neurotransmission, leading to improvements in cognitive performance and memory.^[2][3] Evidence from animal studies indicates that both 5-HT₆ receptor antagonists and agonists can paradoxically exertprocognitive, antidepressant, andanxiolytic effects, demonstrates the complex pharmacology of this receptor class.^[2][3]

Despite promising preclinical results, several selective 5-HT₆ receptor antagonists (e.g.,idalopirdine,intepirdine) have failed to demonstrate significant cognitive benefits in late-stage clinical trials for Alzheimer’s disease, possibly due to the complexity of the disorder and the need for multitarget approaches.^[3] Recent advances in drug design, such as the development of neutral antagonists and multitargetligands, may offer new opportunities for therapeutic intervention.^[4][5]

Clinical trials for ABT-354 have focused on assessing its safety, tolerability, andpharmacokinetics in patients with mild-to-moderate Alzheimer’s disease who are concurrently receiving stable doses ofacetylcholinesterase inhibitors.^[6] These studies included participants aged 55 to 90 years and employed multiple dosing regimens.^[6]

• 5-HT6 antagonists
• Benzamides
• Experimental drugs
• Guanidines
• Thiophenes
• Sulfonamides
• Pyrazoles
• Ethyl compounds

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