143726-85-6Relevant articles and documents
RADIATION-SENSITIVE RESIN COMPOSITION, RESIST PATTERN-FORMING METHOD, COMPOUND AND METHOD OF GENERATING ACID
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Paragraph 0277; 0280, (2020/11/30)
A radiation-sensitive resin composition contains: a polymer that includes a structural unit including an acid-labile group; and a radiation-sensitive acid generating agent. The radiation-sensitive acid generating agent includes a sulfonate anion and a rad
Examination of acylated 4-aminopiperidine-4-carboxylic acid residues in the phosphotyrosyl+1 position of Grb2 SH2 domain-binding tripeptides
Kang, Sang-Uk,Won, Jun Choi,Oishi, Shinya,Lee, Kyeong,Karki, Rajeshri G.,Worthy, Karen M.,Bindu, Lakshman K.,Nicklaus, Marc C.,Fisher, Robert J.,Burke Jr., Terrence R.
, p. 1978 - 1982 (2007/10/03)
A 4-aminopiperidine-4-carboxylic acid residue was placed in the pTyr+1 position of a Grb2 SH2 domain-binding peptide to form a general platform, which was then acylated with a variety of groups to yield a library of compounds designed to explore potential
Design, synthesis, and proposed active site binding analysis of monocyclic 2-azetidinone inhibitors of prostate specific antigen
Adlington,Baldwin,Becker,Chen,Cheng,Cooper,Hermann,Howe,McCoull,McNulty,Neubauer,Pritchard
, p. 1491 - 1508 (2007/10/03)
A homology derived molecular model of prostate specific antigen (PSA) was created and refined. The active site region was investigated for specific interacting functionality and a binding model postulated for the novel 2-azetidinone acyl enzyme inhibitor 1 (IC50 = 8.98 ± 0.90 μM) which was used as a lead compound in this study. A single low energy conformation structure II (Figure 2) was adopted as most likely to represent binding after minimization and dynamics calculations. Systematic analysis of the binding importance of all three side chains appended to the 2-azetidinone was conducted by the synthesis of several analogues. A proposed salt bridge to Lys-145 with 4 (IC50 = 5.84 ± 0.92 μM) gave improved inhibition, but generally the binding of the N-1 side chain in a specific secondary aromatic binding site did not tolerate much structural alteration. A hydrophobic interaction of the C-4 side chain afforded inhibitor 6 (IC50 = 1.43 ± 0.19 μM), and polar functionality could also be added in a proposed interaction with Gln-166 in 5 (IC50 = 1.34 ± 0.05 μM). Reversal of the C-4 ester connectivity furnished inhibitors 7 (IC50 = 1.59 ± 0.15 μM), 11 IC50 = 3.08 ± 0.41 μM) and 13 (IC50 = 2.19 ± 0.36 Mμ) which were perceived to bind to PSA by a rotation of 180° relative to the C-4 ester of normal connectivity. Incorporation of hydroxyl functionality into the C-3 side chain provided 16 IC50 = 348 ± 50 nM) with the greatest increase in PSA inhibition by a single modification. Multiple copy simultaneous search (MCSS) analysis of the PSA active site further supported our model and suggested that 18 would bind strongly. Asymmetric synthesis yielded 18 (IC50 = 226 ± 10 nM) as the most potent inhibitor of PSA reported to date. It is concluded that our design approach has been successful in developing PSA inhibitors and could also be applied to the inhibition of other enzymes, especially in the absence of crystallographic information.
