This review describes the various manifestations of the pyrimidine system (alkylated, glycosylated, benzo-annelated.). These comprise pyrimidine nucleosides as well as alkaloids and antibiotics – some of them have been discovered and isolated from natural sources already long time ago, others have been reported very recently. A short overview on pyrimidine syntheses (prebiotic synthesis, biosynthesis, and metabolism) is given. The biological activities of most of the pyrimidine analogs are briefly described, and, in some cases, syntheses are formulated.

Pyrimidine as constituent of natural biologically active compounds.

Synthesis of purines under possible primitive earth conditions. II. Purine intermediates from hydrogen cyanide.

Soluble guanylate cyclase (sGC) is a key signal-transduction enzyme activated by nitric oxide (NO). Impairments of the NO-sGC signaling pathway have been implicated in the pathogenesis of cardiovascular and other diseases. Direct stimulation of sGC represents a promising therapeutic strategy particularly for the treatment of pulmonary hypertension (PH), a disabling disease associated with a poor prognosis. Previous sGC stimulators such as the pyrazolopyridines BAY 41-2272 and BAY 41-8543 demonstrated beneficial effects in experimental models of PH, but were associated with unfavorable drug metabolism and pharmacokinetic (DMPK) properties. Herein we disclose an extended SAR exploration of this compound class to address these issues. Our efforts led to the identification of the potent sGC stimulator riociguat, which exhibits an improved DMPK profile and exerts strong effects on pulmonary hemodynamics and exercise capacity in patients with PH. Riociguat is currently being investigated in phase III clinical trials for the oral treatment of PH.

Discovery of Riociguat (BAY 63-2521): A Potent, Oral Stimulator of Soluble Guanylate Cyclase for the Treatment of Pulmonary Hypertension

Nucleotide composition of soluble ribonucleic acid from Escherichia coli

A. R. Todd

Papers

100. Experiments on the synthesis of purine nucleosides. Part I. Model experiments on the synthesis of 9-alkylpurines

101. Experiments on the synthesis of purine nucleosides. Part II. A new and convenient synthesis of adenine

85. Experiments on the synthesis of purine nucleosides. Part VI. The synthesis of 9-d-xylosido-2-methyladenine and of 6-d-xylosidamino-2-methylpurine

151. Experiments on the synthesis of purine nucleosides. Part III. 4-Glycosidaminopyrimidines