Water-soluble PDE4 inhibitors for the treatment of dry eye.
PDE4 inhibitors have the potential to alleviate the symptoms and underlying inflammation associated with dry eye. Disclosed herein is the development of a novel series of water-soluble PDE4 inhibitors. Our studies led to the discovery of coumarin 18, which is effective in a rabbit model of dry eye and a tear secretion test in rats.
Govek
Steven P
SP
Kalypsys, Inc., 10420 Wateridge Circle, San Diego, CA 92121, United States. sgovek@san.rr.com
Oshiro
Guy
G
Anzola
John V
JV
Beauregard
Clay
C
Chen
Jasmine
J
Coyle
Avery R
AR
Gamache
Daniel A
DA
Hellberg
Mark R
MR
Hsien
Jennifer N
JN
Lerch
Julia M
JM
Liao
John C
JC
Malecha
James W
JW
Staszewski
Lena M
LM
Thomas
David J
DJ
Yanni
John M
JM
Noble
Stewart A
SA
Shiau
Andrew K
AK
D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D001665:Binding Sites; D003198:Computer Simulation; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000188:drug therapy; D058988:Phosphodiesterase 4 Inhibitors; D011817:Rabbits; D051381:Rats; D014867:Water / Q000737:chemistry*
D000893:Anti-Inflammatory Agents; D003374:Coumarins; D058988:Phosphodiesterase 4 Inhibitors; D014867:Water; D015761:4-Aminopyridine; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4