title: 1,2-Diamines as inhibitors of co-activator associated arginine methyltransferase 1 (CARM1).
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, MethylGene Inc, Montreal, Quebec, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Therrien
authors.forename: Guillaume
authors.initials: G
authors.lastname: Larouche
authors.forename: Sukhdev
authors.initials: S
authors.lastname: Manku
authors.forename: Martin
authors.initials: M
authors.lastname: Allan
authors.forename: Natalie
authors.initials: N
authors.lastname: Nguyen
authors.forename: Sylvia
authors.initials: S
authors.lastname: Styhler
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Robert
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Goulet
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Besterman
authors.forename: Hannah
authors.initials: H
authors.lastname: Nguyen
authors.forename: Amal
authors.initials: A
authors.lastname: Wahhab
mesh_terms: D003959:Diamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D011484:Protein-Arginine N-Methyltransferases / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D003959:Diamines; D004791:Enzyme Inhibitors; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1