Discovery and structure-activity study of a novel benzoxaborole anti-inflammatory agent (AN2728) for the potential topical treatment of psoriasis and atopic dermatitis.
A series of phenoxy benzoxaboroles were synthesized and screened for their inhibitory activity against PDE4 and cytokine release. 5-(4-Cyanophenoxy)-2,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2728) showed potent activity both in vitro and in vivo. This compound is now in clinical development for the topical treatment of psoriasis and being pursued for the topical treatment of atopic dermatitis.
Akama
Tsutomu
T
Anacor Pharmaceuticals, Inc, Palo Alto, CA 94303, USA. takama@anacor.com
Baker
Stephen J
SJ
Zhang
Yong-Kang
YK
Hernandez
Vincent
V
Zhou
Huchen
H
Sanders
Virginia
V
Freund
Yvonne
Y
Kimura
Richard
R
Maples
Kirk R
KR
Plattner
Jacob J
JJ
D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry*; D001896:Boron Compounds / Q000008:administration & dosage / Q000737:chemistry*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage / Q000737:chemistry*; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000473:pathology; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000737:chemistry*; D004487:Edema / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D051379:Mice; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship; D020298:U937 Cells
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001896:Boron Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003879:Dermatologic Agents; C543085:crisaborole