Search

A novel cyclic GRF analog, cyclo(Asp8-Lys12)-[Asp8,Ala15]-GRF(1-29)-NH2, i.e. cyclo8,12[Asp8,Ala15]-GRF(1-29)-NH2, was synthesized by the solid phase procedure and found to retain significant biological activity. Solid phase cyclization of Asp8 to Lys12 proceeded rapidly (approximately 2 h) using the BOP reagent. Substitution of Ala2 with D-Ala2 and/or NH2-terminal replacement (desNH2-Tyr1 or N-MeTyr1) in the cyclo8,12[Asp8,Ala15]-GRF(1-29)-NH2 system resulted in highly potent analogs that were also active in vivo. Conformational analysis (circular dichroism and molecular dynamics calculations based on NOE-derived distance constraints) demonstrated that cyclo8,12[Asp8,Ala15]-GRF(1-29)-NH2 contains a long alpha-helical segment even in aqueous solution. A series of cyclo8,12 stereoisomers containing D-Asp8 and/or D-Lys12 were prepared and also found to be highly potent and to retain significant alpha-helical conformation. The high biological activity of cyclo8,12[N-MeTyr1,D-Ala2,Asp8,Ala15]-GRF(1-29)- NH2 may be explained on the basis of retention of a preferred bioactive conformation.

Thirteen Schiff base salts in the class of compounds represented by retinal pyrrolidinium perchlorate were prepared (most of them for the first time), fully characterized analytically and spectroscopically, and examined in the 30–100 GHz range with respect to their putative ability to absorb radar signals. While some signal loss was noted with salts having I3− counterions, the compounds of this class show negligible potential as components of radar-absorbing coating systems.

1,3-Dimethyl-1,2-dihydro-2-imino-4(3H)pyrimidinone (1,3-dimethylisocytosine) was prepared by methylation of 2-amino-3-methyl-4(3H)pyrimidinone and was degraded in alkaline solution to a mixture of 3-methyl-2-methylamino-4(3H)pyrimidinone, 1,3-dimethyl-2,4-(1H,3H)pyrimid-indione, 2-methylamino-l-methyl-4(1H)pyrimidinone, 1-methyl-2,4-(1H,3H)pyrimidindione and 3-methyl-2,4-(1H,3H)pyrimidindione. Thiation of the title compound gave both 1,2-dihydro-1,3-dimethyl-2-thio-4(3H)pyrimidinone and 1,3-dimethyl-2,4-(1H,3H)pyrimidinedithione. The title compound is a tautomerically fixed pyrimidine and its uv spectra were compared with related compounds, notably 3-methyl-2-dimethylarnino-4(3H)pyrimidinone which is also tautomerically fixed.

The synthesis and some chemical reactions of various iodonitroimidazoles and methods of distinguishing between the 4- and 5- nitro derivatives by UV and pK measurements are described.