Abstract:
:The inhibition of the UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase (LpxC) represents a promising strategy to combat infections caused by multidrug-resistant Gram-negative bacteria. In order to elucidate the functional groups being important for the inhibition of LpxC, the structure of our previously reported hydroxamic acid 4 should be systematically varied. Therefore, a series of benzyloxyacetohydroxamic acids was prepared, of which the diphenylacetylene derivatives 28 (Ki=95nM) and 21 (Ki=66nM) were the most potent inhibitors of Escherichia coli LpxC. These compounds could be synthesized in a stereoselective manner employing a Sharpless asymmetric dihydroxylation and a Sonogashira coupling in the key steps. The obtained structure-activity relationships could be rationalized by molecular docking studies.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Szermerski M,Melesina J,Wichapong K,Löppenberg M,Jose J,Sippl W,Holl Rdoi
10.1016/j.bmc.2013.12.057subject
Has Abstractpub_date
2014-02-01 00:00:00pages
1016-28issue
3eissn
0968-0896issn
1464-3391pii
S0968-0896(13)01065-1journal_volume
22pub_type
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