- Blockade of STAT3 activation by sorafenib derivatives through enhancing SHP-1 phosphatase activity
-
Previously, we demonstrated that the multiple kinase inhibitor sorafenib mediates the repression of phospho-STAT3 in hepatocellular carcinoma cells. In this study, we used this kinase-independent mechanism as a molecular basis to use sorafenib as scaffold to develop a novel class of SHP-1-activating agents. The proof of principle of this premise was provided by SC-1, which on replacement of N-methylpicolinamide by a phenylcyano group showed abolished kinase activity while retaining phospho-STAT3 repressive activity. Structural optimization of SC-1 led to compound 6, which repressed phospho-STAT3 through SHP-1 activation and inhibited PLC5 cell proliferation at sub-micromolar potency. In light of the pivotal role of phospho-STAT3 in promoting tumorigenesis and drug resistance, this novel SHP-1-activating agent may have therapeutic relevance in cancer therapy.
- Hsu, Cheng-Yi,Liu, Chun-Yu,Shiau, Chung-Wai,Chen, Kuen-Feng,Chen, Pei-Jer,Tai, Wei-Tien,Huang, Jui-Wen,Kim, Inki
-
p. 220 - 227,8
(2020/07/31)
-
- Pesticidal esters of amino acids
-
Novel diastereomeric esters of amino acids, novel intermediates therefor, synthesis thereof, and the use of said esters for the control of pests.
- -
-
-
- Cyano-3-phenoxybenzyl N-1-(1-naphthyl) ethylcarbamate
-
Diastereomeric esters of 2-phenylamino-3-methylbutanoic acids, novel intermediates therefor, synthesis thereof, and the use of said esters for the control of pests.
- -
-
-
- Enantiomerically Pure Lactones. 3. Synthesis of and Stereospecific Conjugate Additions to α,β-Unsaturated Lactones
-
A general synthetic approach to both enantiomers of α,β-unsaturated lactones of general formula 1 has been devised, the first synthesis of the naturally occuring antipode of massoilactone (1b) exemplifying the approach.Interestingly, the specific rotation of massoilactone (and its enantiomer) is higher than that of the natural material isolated from formicine ants.A key step in the sequence involves chromatographic separation of rationally selected diastereomeric derivatives of racemic intermediates. Compounding the utility of an approach to optically active, type 1 lactones is the observation that conjugate additions of organometallic reagents to such lactones proceed with a high degree of stereospecificity, affording lactones of general formula 2. The conformational behavior of lactone 1a is considered as is the solvation of δ-lactones by fluoroalcoholic chiral solvating agents such as 2,2,2-trifluoro-1-(9-anthryl)ethanol (8).
- Pirkle, William H.,Adams, Paul E.
-
p. 4117 - 4121
(2007/10/02)
-
- Synthesis of 1,2,3-Decanetriol Stereoisomers
-
The synthesis and 13C NMR spectra of 1,2,3-decanetriol stereoisomers are described. High enantiomeric purity triols are obtained by chromatographic resolution of diastereomeric carbamates derived from 1-decyn-3-ol and (R)-1-(1-naphthyl)ethylamine. The triol is obtained by conversion of the acetylene to an olefin, stereoselective epoxidation with tert-butyl hydroperoxide and a transition-metal catalyst, and stereospecific ring opening of the epoxide with KOH.
- Rinaldi, Peter L.,Levy, George C.
-
p. 4348 - 4351
(2007/10/02)
-
- Enantiomerically Pure Lactones. 2. Approaches to Cis or Trans Multicyclic Lactones
-
Enantiomerically pure bicyclic lactones 1-3 and tricyclic lactones 4 and 5 have been prepared by either of two procedures, each hinging upon the liquid chromatographic seperation of rationally selected diastereomeric derivatives.After seperation, the diastereomers are converted by a simple high-yield reaction sequence to the enantiomeric multiring lactones, none of which has been previously reported in optically active form. The relative strengths and weaknesses of each approach are discussed.Lactones 4 and 5 were α-methylated, these derivatives being suitable for the determination of enantiomeric purity and absolute configuration using the chiral solvating agent (S)-(+)-2,2,2-trifluoro-1-(9-anthryl)ethanol.
- Pirkle, William H.,Adams, Paul E.
-
p. 4111 - 4117
(2007/10/02)
-
