Identification of a novel boron-containing antibacterial agent (AN0128) with anti-inflammatory activity, for the potential treatment of cutaneous diseases.
A series of borinic acid picolinate esters were synthesized and screened for their minimum inhibitory concentration (MIC) against Gram-positive and -negative bacteria. Our lead compounds were then screened for anti-inflammatory activity. From these studies, we identified 3-hydroxypyridine-2-carbonyloxy-bis(3-chloro-4-methylphenyl)borane (2g, AN0128) as having the best combination of anti-bacterial and anti-inflammatory activities. This compound is now in clinical development for dermatological conditions.
Baker
Stephen J
SJ
Anacor Pharmaceuticals, Inc., 1060 E. Meadow Circle, Palo Alto, CA 94303, USA. sbaker@anacor.com <sbaker@anacor.com>
Akama
Tsutomu
T
Zhang
Yong-Kang
YK
Sauro
Vittorio
V
Pandit
Chetan
C
Singh
Rajeshwar
R
Kully
Maureen
M
Khan
Jehangir
J
Plattner
Jacob J
JJ
Benkovic
Stephen J
SJ
Lee
Ving
V
Maples
Kirk R
KR
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001880:Boranes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001895:Boron / Q000737:chemistry*; D001896:Boron Compounds / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D004952:Esters / Q000737:chemistry; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012871:Skin Diseases / Q000188:drug therapy; D013329:Structure-Activity Relationship
C515885:3-hydroxypyridine-2-carbonyloxy-bis(3-chloro-4-methylphenyl)borane; D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D001880:Boranes; D001896:Boron Compounds; D016207:Cytokines; D004952:Esters; D011725:Pyridines; C035757:diphenylborate; D001895:Boron