CGP 47969A is a novel piperazine derivative that inhibits the synthesis of inflammatory cytokines, such as interleukin-1 alpha (IL-1), IL-1 beta and tumor necrosis factor alpha (TNF), in human monocytes stimulated with lipopolysaccharide (LPS), zymosan or IL-1 itself. IC50 values are in the range of 0.3-5 mumol/l. CGP 47969A does not inhibit total protein or RNA synthesis indicating selectivity for cytokine inhibition. CGP 47969A exerts its inhibitory effect at a post-transcriptional level, most probably by reducing translational efficiency of IL-beta mRNA, as steady-state levels of IL-1 beta mRNA are not inhibited while the primary translation product, the 31 kD IL-1 beta precursor molecule, is dose-dependently inhibited by CGP 47969A. The compound is devoid of cyclooxygenase and phospholipase A2 inhibitory activity but efficiently inhibits the generation of PGE2 and LTC4 in zymosan-stimulated mouse macrophages with an IC50 of 1.2 and 0.6 mumol/l, respectively. Antagonism of IL-1 and/or TNF is thought to have a beneficial effect on the course of inflammatory diseases. CGP 47969A may therefore represent a mechanistically new approach to the treatment of such diseases.

then decomposes into the acetylene derivative, chloride ion, and formic acid. In an analogous manner, we obtained phenylacetylene from acetophenone via chlorocinnamaldehyde and p-methoxyphenylacetylene from p-methoxyaoetophenone via (3-chloro-p-methoxycinnamaldehyde.The new reaction makes it possible to prepare many acetylene derivatives relatively easily. Received, Dcccrnber 14th. 1962 [Z 411/240 lE] [IWe have found that primary carboxamides may be. condensed with vinylene carbonate (I) [I] in polyphosphoric acid to yield 2-substituted oxazoles (2). f 1) 12)Thus, condensation of equimolar quantities of benwmide and vinylene carbonate in polyphosphoric acid (2 hrs. at 165-170°C) gave 2-phenyloxazole (b.p. 100-101 "/12 mm.) in 34% yield [2]. The corresponding reaction with m-nitrobenzamide gave 3-nitrophenyl-2'sxazole (m.p. 99-99.5 "C) in 10% yield, and that with othlorobenzamide afforded 2chlorophenyl-2'-oxazole (b.p. 100-105 OC10.6 mm) in 6% yield. The reaction failed, however, when the following amides were employed : phenoxyacetamide, phenylacetamide, pmethylbenzamide, and salicylamide. Picolinic amide gave 2-(2'-pyridyl)oxazole in about 2 yield. The formation of the oxazole m a y be accounted for by the following mechanism:The consistently moderate yields could not so far be significantly improved when the reaction conditions were changed. Because of its simplicity, however, the present new synthesis appears to deserve further investigation. Received. December 14th. 1962 [Z 413/239 IE] [I] R. W. Addor, Ph. D. thesis (No. 1485), Ohio State University (1954); M. S. Newman and R. W. Addor, I. Amer. chem. Soc. 77, 3789 (1955). We thank Dr. H. Orth of the ClBA AG., Basel, for a specimen of this compound. 12) J . University Press Princeton, N.J., 1949, p. 704. as well as W. E. Cuss, J. Amer. chem. Soc. 64,785 (1942) give a b.p. of 223-225 "C for 2-phenyl o x~l e .Lithium triphenylstanniine Li . Sn(GHS)3 Ill was prepared readily from triphenylchlorostann:tm and lithium in tetrahydrofuran. It is an efkient nucleophilic reagent and undergoes stepwise reactions with sulfur, selenium, and tellurium in tetrahydrofuran at room temperature. n (GH&SnLi + X , + n (GH3.6n-X--Li (X = S. Se, Tc)The pure monochalkogenide (2) is difficult to isolate and is formed only in the presence of a large excess of (I) (stoichiometric quantities of reactants yield a mixture of (CaHs)3s&Li products). Solutions of (2) are very reactive and are sensitive toward air and heat (condensation to Li2S and thioether if X = S). With triphenylchlorostannane, good yields of hexaphenylditin sulfide, hexaphenylditin selenide, and hexaphenylditin telluride (m.p. 148OC) are obtainable. With benzoyl chloride, the sulfur compound readily forms Lriphenyltin thiobenzoate ( c & i )~S n -S -c o -C~H~ (m.p. I08 "C). By reaction between (2) and triplienylbrornogermanium or triphenylchlorolead : (GH&SnXLi + BrOe(C&ls)3 -b LiBr + (C&ls)3snXGe(C#s)~ such compounds as (c&t~)3SnSc;e(C6Hs)3 (m. p. 135 "C), (GH5)3 (m.p. 138OC) are obtaincd; the methyl analogues of these c...

A re-ex8mh18tio11 of the -C NMR spectra of commrand~ 'one and isatin with the aid of proton-coupled -C NMR spectra and selective proton dewupling experiments is reported.The carbon chemical shifts of coumarandione (1) have recently been published.' Since the chemical shift data disagreed extensively with our data on related compounds, we repeated the preparation' of 1 and measured its 13C NMR spectrum, given in Table 1 together with the data of isatin (2). The assignment of the

SUMMARYFrom GILBERT & GARETT'S~) data on the solubility of a-Be(OH), in diluted acids, the following equilibrium constants have been calculated (aso, ionic strength zero) : a-Be(OH), + 2 H+ = Be2+ + 2 H,O; log * K s o = -6,86 & 0,05 3 a-Be(OH), + 3 H+ = Be,(OH):f + 3 H,O; log *Ks33 = -11,67 0,05 3 Be2+ + 3 H20 = Be,(OH):+ + 3 H+; log */I 33 = -8,9 5 0,l.

its composition, and its IR, UV, and HI-NMR spectra. On complex formation, the C=O band of tocoquinone is displaced by 114 cm-1 from 1647 to 1533 cm-1 and bands at 779, 824, and 860 cm-1 characteristic of symmetrically x-complexed cycloocta-1 ,S-diene appear. The UV spectrum closely resembles that of cycloocta-1 ,5-diene-Ni(O)duroquinone. In the proton resonance spectrum, the signal due to the four olefinic protons of the x-complexed cyclooctadiene appears at T = 2.28, while that due to aliphatic protons of the diene is found at T = 1.90 (40 x 106 cps). The remainder of the NMR spectrum resembles that of DL-a-tocoquinone. The compound, which is stable in air for considerable periods, is soluble in benzene, halogenated hydrocarbons, alcohols, ethers, and acetone, but is insoluble in water. It is the first well-defined x-complex of a transition metal with a natural product; in view of the possible carcinogenic properties of nickel, the physiological evaluation of (I), which is in progress, promises to be of considerable interest. Received, May 21st. 1962 [Z 289/120 IE] Received, May 21st. 1962 [Z 284/118 IE] 111 Cf. R. G o d and A. Meuwsen, Chem. Ber. 92, 2525 (1959);