204919-75-5Relevant articles and documents
Acetylenic Replacement of Albicidin's Methacrylamide Residue Circumvents Detrimental E/Z Photoisomerization and Preserves Antibacterial Activity
Behroz, Iraj,Kleebauer, Leonardo,Hommernick, Kay,Seidel, Maria,Gr?tz, Stefan,Mainz, Andi,Weston, John B.,Süssmuth, Roderich D.
, p. 9077 - 9086 (2021/05/27)
The natural product albicidin is a highly potent inhibitor of bacterial DNA gyrase. Its outstanding activity, particularly against Gram-negative pathogens, qualifies it as a promising lead structure in the search for new antibacterial drugs. However, as we show here, the N-terminal cinnamoyl moiety of albicidin is susceptible to photochemical E/Z isomerization. Moreover, the newly formed Z isomer exhibits significantly reduced antibacterial activity, which hampers the development and biological evaluation of albicidin and potent derivatives thereof. Hence, we synthesized 13 different variants of albicidin in which the vulnerable para-coumaric acid moiety was replaced; this yielded photostable analogues. Biological activity assays revealed that diaryl alkyne analogues exhibited virtually undiminished antibacterial efficacy. This promising scaffold will therefore serve as a blueprint for the design of a potent albicidin-based drug.
Development of a novel, CNS-penetrant, metabotropic glutamate receptor 3 (mGlu3) NAM probe (ML289) derived from a closely related mGlu 5 PAM
Sheffler, Douglas J.,Wenthur, Cody J.,Bruner, Joshua A.,Carrington, Sheridan J.S.,Vinson, Paige N.,Gogi, Kiran K.,Blobaum, Anna L.,Morrison, Ryan D.,Vamos, Mitchell,Cosford, Nicholas D.P.,Stauffer, Shaun R.,Scott Daniels,Niswender, Colleen M.,Jeffrey Conn,Lindsley, Craig W.
scheme or table, p. 3921 - 3925 (2012/07/14)
Herein we report the discovery and SAR of a novel metabotropic glutamate receptor 3 (mGlu3) NAM probe (ML289) with 15-fold selectivity versus mGlu2. The mGlu3 NAM was discovered via a 'molecular switch' from a closely related, potent mGlu5 positive allosteric modulator (PAM), VU0092273. This NAM (VU0463597, ML289) displays an IC 50 value of 0.66 μM and is inactive against mGlu5.
