1,2-Diamines as inhibitors of co-activator associated arginine methyltransferase 1 (CARM1)

We have identified the N 1-benzyl- N 2-methylethane-1,2-diamine unit as a substitute for the ( S)-alanine benzylamide moiety for the design of co-activator associated arginine methyltransferase 1 (CARM1) inhibitors. The potency of these inhibitors is in the same order of magnitude as their predecess...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2009-12, Vol.19 (23), p.6725-6732
Main Authors: Therrien, Eric, Larouche, Guillaume, Manku, Sukhdev, Allan, Martin, Nguyen, Natalie, Styhler, Sylvia, Robert, Marie-France, Goulet, Anne-Christine, Besterman, Jeffrey M., Nguyen, Hannah, Wahhab, Amal
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
CARM1 inhibitors
Co-activator associated arginine methyltransferase 1
Diamines - chemical synthesis
Diamines - chemistry
Diamines - pharmacology
Drug Design
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
General aspects
Histone methyltransferase inhibitors
Medical sciences
Models, Molecular
Molecular Structure
Pharmacology. Drug treatments
PRMT4 inhibitors
Protein-Arginine N-Methyltransferases - antagonists & inhibitors
Stereoisomerism
Structure-Activity Relationship
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Summary:We have identified the N 1-benzyl- N 2-methylethane-1,2-diamine unit as a substitute for the ( S)-alanine benzylamide moiety for the design of co-activator associated arginine methyltransferase 1 (CARM1) inhibitors. The potency of these inhibitors is in the same order of magnitude as their predecessors and their clearance, volume of distribution, and half lives were greatly improved. We have identified the N 1-benzyl- N 2-methylethane-1,2-diamine unit as a substitute for the ( S)-alanine benzylamide moiety for the design of co-activator associated arginine methyltransferase 1 (CARM1) inhibitors. The potency of these inhibitors is in the same order of magnitude as their predecessors and their clearance, volume of distribution, and half lives were greatly improved.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2009.09.110