N-Hydroxybenzimidazole Inhibitors of the Transcription Factor LcrF in Yersinia: Novel Antivirulence Agents
摘要:
LcrF, a multiple adaptational response (MAR) transcription factor, regulates virulence in Yersinia pestis and Yersinia pseudotuberculosis. In a search for small molecule inhibitors of LcrF, an acrylic amide series of N-hydroxybenzimidazoles was synthesized and the SAR (structure-activity relationship) was examined, Selected test compounds demonstrated inhibitory activity in a primary cell-free LcrF-DNA binding assay as well as in a secondary whole cell assay (type III secretion system dependent Y. pseudotuberculosis cytotoxicity assay). The inhibitors exhibited no measurable antibacterial activity in vitro, confirming that they do not target bacterial growth. These results demonstrate that N-hydroxy-benzimidazole inhibitors, exemplified by 14, 22, and 36, are effective antivirulence agents and have the potential to prevent infections caused by Yersinia spp.
The present invention relates to certain novel compounds of Formula (I):
and methods for preparing these compounds, compositions, intermediates and derivatives thereof and for the treatment of prokineticin 1 or prokinetin 1 receptor mediated disorders.
PROKINETICIN 1 RECEPTOR ANTAGONISTS FOR THE TREATMENT OF PAIN
申请人:Flores Christopher M.
公开号:US20110319400A1
公开(公告)日:2011-12-29
Disclosed are compounds, compositions and methods for treating pain, including inflammatory, visceral, and acute pain. Such compounds are represented by Formula (I) as follows:
wherein A
1
, L
1
, D, and Q are defined herein.
The present invention relates to a compound which has a glucokinase-activating effect and is useful as a therapeutic agent for diabetes mellitus, being represented by a formula (I):
[wherein X
1
represents a nitrogen atom, sulfur atom, oxygen atom or the like; R
1
represents a 6- to 10-membered aryl group, 5- to 7-membered heteroaryl group or the like; D represents an oxygen atom or sulfur atom; R and R
3
are the same or different, each representing a hydrogen atom, lower alkyl group or the like; a formula (II)
represents an optionally substituted 5- to 7-membered heteroaryl group or the like; a formula (III)
represents a monocyclic or bicyclic heteroaryl group] or a pharmaceutically acceptable salt thereof.
The present invention is directed to novel thia-tetraazaacenaphthylene compounds of Formula (I):
and pharmaceutically acceptable forms thereof and their synthesis and use as inhibitors of ATP-protein kinase interactions.
The present invention relates to a compound which has a glucokinase-activating effect and is useful as a therapeutic agent for diabetes mellitus, being represented by a formula (I):
[wherein X
1
represents a nitrogen atom, sulfur atom, oxygen atom or the like; R
1
represents a 6- to 10-membered aryl group, 5- to 7-membered heteroaryl group or the like; D represents an oxygen atom or sulfur atom; R
2
and R
3
are the same or different, each representing a hydrogen atom, lower alkyl group or the like; a formula (II)
represents an optionally substituted 5- to 7-membered heteroaryl group or the like; a formula (III)
represents a monocyclic or bicyclic heteroaryl group] or a pharmaceutically acceptable salt thereof.