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A series of novel chiral 7-(7-amino-5-azaspiro[2.4]heptan-4-yl)-8-chloro-1-(2-fluo rocyclopropyl)- quinolones were synthesized as a continuation of a research project of 1-(2-fluorocyclopropyl)-quinolones by considering stereochemical and physicochemical properties of the molecule. Absolute configurations of the 1-(cis-2-fluorocyclopropyl) moiety and the 7-(7-amino-5-azaspiro-[2.4]heptan-5-yl) moiety were determined by X-ray crystallographic analysis. Stereochemical structure-activity relationship studies indicated that 1-[(1R,2S)-2-fluorocyclopropyl] and 7-[(7S)-amino-5-azaspiro[2.4]heptan-5-yl] derivatives are more potent against Gram-positive and Gram-negative bacteria than the other stereoisomers and 7-[(7S)-7-amino-5-azaspiro[2.4]-heptan-5-yl]-8-chloro-1-[(1R ,2S)-2- fluorocyclopropyl]quinolone (33) is the most potent of all stereoisomers. Pharmacokinetic profiles and physicochemical properties of the selected compounds were also examined, and it was found that 33 (DU-6859a) possesses moderate lipophilicity and good pharmacokinetic profiles.

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rythropoietin (EPO), the kidney hormone regulating erythrocyte production, activates the erythropoietin receptor (EPOR), resulting in antiapoptosis. To investigate the clinical significance of EPOR expressed in neuronal cells of the brain, EPO was administered to patients within 8 hours of the onset of stroke symptoms, which ultimately resulted in the reduction of cerebral infarct size and improvement of functional neurologic performance. 1 Rodents treated with EPO in an animal model of myocardial ischemia and infarction recently demonstrated superior myocardial function. 2,3 The expression of the EPOR was shown for a variety of rodent and rabbit primary and permanent cardiomyocyte cell lines. But, as noted by several investigators, 2,3 proof of the presence of the EPOR in the adult human heart is missing.To overcome this deficit, we investigated adult human ventricular and atrial tissue for the expression of the EPOR.

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