The chemical transliteration of Plato's universe-the dodecahedrane-has been synthesized in 23 steps. The key stages of the sequence starting from dichloro diester 2 involve the following: (a) reduction-monoakylation of 2 using chloromethyl phenyl ether to give 7; (b) photocyclization of aldehyde 12 without interference from the geminal side chain; (c) retro-aldol cleavage of keto aldehyde 15; and (d) catalytic dehydrogenation of 19. The single-peak nature of the 'H and 13C NMR spectra of 1 conforms to its ultrahigh (I,,) symmetry. The spherical hydrocarbon exhibits three infrared-active and eight Raman-active bands. The unique physical behavior of 1 upon heating to temperatures above 400 OC is detailed.For centuries, the dodecahedron has been esteemed as the most complex and aesthetically pleasing of the perfect solids of antiquity. In more recent times, scientists have come to regard its molecular transliteration, dodecahedrane (C2,,HH,, 1), as the "Mount Everest u

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A series of oxamyl dipeptides were optimized for pan caspase inhibition, anti-apoptotic cellular activity and in vivo efficacy. This structure-activity relationship study focused on the P4 oxamides and warhead moieties. Primarily on the basis of in vitro data, inhibitors were selected for study in a murine model of alpha-Fas-induced liver injury. IDN-6556 (1) was further profiled in additional in vivo models and pharmacokinetic studies. This first-in-class caspase inhibitor is now the subject of two Phase II clinical trials, evaluating its safety and efficacy for use in liver disease.

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The structure-activity relationship among a series of novel pyrazolidinone antibacterial agents is described. Specifically, the effect of modification of the side chain attached to the nitrogen at C-7 was explored in an attempt to improve the potency and spectrum of activity. This approach was successful in identifying several compounds having good in vitro profiles. These top candidates were then evaluated for their activity in vivo, and their pharmacokinetic behavior in various animal models was explored. This information proved critical for the identification of candidates for clinical evaluation.