Stuart:
And, if you search using the inventor's names as I discussed, you turn up stuff like this.......
J Med Chem 1998 May 21;41(11):1970-9
(+/-)-trans-2-[3-methoxy-4-(4-chlorophenylthioethoxy)-5-(N-methyl-N-
hydroxyureidyl)methylphenyl]-5-(3,4,
5-trimethoxyphenyl)tetrahydrofuran (CMI-392), a potent dual
5-lipoxygenase inhibitor and platelet-activating factor receptor antagonist.
Cai X, Scannell RT, Yaeger D, Hussoin MS, Killian DB, Qian C, Eckman J, Hwang SB, Libertine-Garahan L, Yeh
CG, Ip SH, Shen TY
CytoMed, Inc., 840 Memorial Drive, Cambridge, Massachusetts 02139, and Department of Chemistry, University of Virginia,
Charlottesville, Virginia 22903, USA.
By incorporating an N-hydroxyurea functionality onto diaryltetrahydrofurans, a novel series of compounds was investigated as
dual 5-lipoxygenese (5-LO) inhibitor and platelet-activating factor (PAF) receptor antagonist. These dual functional
compounds were evaluated in vitro for 5-LO inhibition in RBL cell extracts and human whole blood, and PAF receptor
antagonism in a receptor binding assay. PAF-induced hemoconcentration and arachidonic acid- and TPA-induced ear edema
in mice were used to determine in vivo activities. The structure-activity relationship analysis to define a preclinical lead is
presented. (+/-)-trans-2-[3-methoxy-4-(4-chlorophenylthioethoxy)-5-(N-methyl- N-h ydroxyureidyl)methylphenyl]-5-(3,4,
5-trimethoxyphenyl)tetrahydrofuran (40, CMI-392) was selected for further study. In the arachidonic acid-induced mouse ear
edema model, 40 was more potent than either zileuton (a 5-LO inhibitor) or BN 50739 (a PAF receptor antagonist), and it
demonstrated the same inhibitory effect as a physical combination of the latter two agents. These results suggest that a single
compound which both inhibits leukotriene synthesis and blocks PAF receptor binding may provide therapeutic advantages over
single-acting agents. The clinical development of compound 40 is in progress.
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at which time, if you're a LKST shareholder, you start to take serious interest.
Thanks again, Rick |
