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 predecessors and their clearance, volume of distribution, and half lives were greatly improved.
Therrien
Eric
E
Department of Medicinal Chemistry, MethylGene Inc, Montreal, Quebec, Canada.
Larouche
Guillaume
G
Manku
Sukhdev
S
Allan
Martin
M
Nguyen
Natalie
N
Styhler
Sylvia
S
Robert
Marie-France
MF
Goulet
Anne-Christine
AC
Besterman
Jeffrey M
JM
Nguyen
Hannah
H
Wahhab
Amal
A
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
D003959:Diamines; D004791:Enzyme Inhibitors; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1