Discovery of the first known small-molecule inhibitors of heme-regulated eukaryotic initiation factor 2alpha (HRI) kinase.
A series of indeno[1,2-c]pyrazoles were discovered to be the first known inhibitors of heme-regulated eukaryotic initiation factor 2alpha (HRI) kinase. The synthesis, structure-activity relationship profile, and in-vitro pharmacological characterization of this inaugural series of HRI kinase inhibitors are detailed.
Johnson & Johnson Pharmaceutical Research and Development, LLC, San Diego, CA 92121, United States. mrosen1@its.jnj.com
Mark D
MD
Rosen
Craig R
CR
Woods
Steven D
SD
Goldberg
Michael D
MD
Hack
A Dawn
AD
Bounds
Young
Y
Yang
Pamela C
PC
Wagaman
Victor K
VK
Phuong
Angela P
AP
Ameriks
Terrance D
TD
Barrett
Kimon C
KC
Kanelakis
Jui Chang
JC
Chuang
Jui
J
Chang
Nigel P
NP
Shankley
Michael H
MH
Rabinowitz
D055808:Drug Discovery; D006418:Heme / Q000378:metabolism*; D007192:Indenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D008970:Molecular Weight; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D007192:Indenes; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D006418:Heme; D019892:eIF-2 Kinase