Identification of 2-arylbenzimidazoles as potent human histamine H4 receptor ligands.
A series of 2-arylbenzimidazoles was synthesized and found to bind with high affinity to the human histamine H(4) receptor. Structure-activity relationships were investigated through library preparation and evaluation as well as traditional medicinal chemistry approaches, leading to the discovery of compounds with single-digit nanomolar affinity for the H(4) receptor.
Lee-Dutra
Alice
A
Johnson & Johnson Pharmaceutical Research and Development, L.L.C. 3210 Merryfield Row, San Diego, CA 92121, USA. alee7@prdus.jnj.com <alee7@prdus.jnj.com>
Arienti
Kristen L
KL
Buzard
Daniel J
DJ
Hack
Michael D
MD
Khatuya
Haripada
H
Desai
Pragnya J
PJ
Nguyen
Steven
S
Thurmond
Robin L
RL
Karlsson
Lars
L
Edwards
James P
JP
Breitenbucher
J Guy
JG
D000447:Aldehydes / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D002384:Catalysis; D003198:Computer Simulation; D006632:Histamine / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*; D011968:Receptors, Histamine / Q000737:chemistry / Q000378:metabolism*; D000074040:Receptors, Histamine H4; D013329:Structure-Activity Relationship
D000447:Aldehydes; D000588:Amines; D001562:Benzimidazoles; C418607:HRH4 protein, human; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D006632:Histamine