Asymmetric 1,3-dipolar cycloaddition reaction of chiral 1-alkyl-1,2-diphospholes with diphenyldiazomethane

The 1,3-dipolar cycloaddition of chiral 1-alkyl-1,2-diphosphacyclopenta-2,4-dienes ((1-(−)-menthyl)oxymethyl-1,2-diphosphole and 1-(+)-neomenthyl-1,2-diphosphole) with diphenyldiazomethane leads to novel P-chiral bicyclic phosphiranes having six chiral centers. The degree of diastereoselectivity depends on the substituent at phosphorus, and dramatically increases in the case of (+)-neomenthyl group (de up to 71%). DFT calculations indicate that the cycloaddition is thermodynamically controlled.

The 1,3-dipolar cycloaddition of chiral 1-alkyl-1,2-diphosphacyclopenta-2,4-dienes with diphenyldiazomethane leads to novel P-chiral bicyclic phosphiranes having six chiral centers.     

Fractionated low-intensity thermotherapy of benign prostatic hyperplasia

120 patients with benign prostatic hyperplasia (BPH) (mean age 65.8 +/- 7.7 years) received fractional low-intensity transurethral microwave thermotherapy (FLITMT). Each patient was exposed to 4 FLITMT procedures with 3-4 day interval (duration--60 min at 48.5-49.9 degrees C, ProsTek 3000 unit, USA). Subjective and objective effects of FLITMT were observed in 87 (82.9%) and 75 (71.4%) patients, respectively. A stable effect on IPSS persisted for 3 years, on acceleration of maximal urination rate--within a year. Moreover, FLITMT was associated with a low frequency of complications. This makes the above thermotherapy usable in all BPH patients without absolute indications for surgical treatment.     

Preconditioning paradigms and pathways in the brain

Preconditioning is a phenomenon in which the brain protects itself against future injury by adapting to low doses of noxious insults. Preconditioning stimuli include ischemia, low doses of endotoxin, hypoxia, hypothermia and hyperthermia, cortical spreading depression, anesthetics, and 3-nitropropionic acid, among others. Understanding of the mechanisms underlying preconditioning has been elusive, but NMDA receptor activation, nitric oxide, inflammatory cytokines, and suppression of the innate immune system appear to have a role. Elucidation of the endogenous cell survival pathways involved in preconditioning has significant clinical implications for preventing neuronal damage in susceptible patients.     

Design and synthesis of human immunodeficiency virus entry inhibitors: sulfonamide as an isostere for the alpha-ketoamide group

The crystal structures of many tertiary alpha-ketoamides reveal an orthogonal arrangement of the two carbonyl groups. Based on the hypothesis that the alpha-ketoamide HIV attachment inhibitor BMS 806 (formally BMS378806, 26) might bind to its gp120 target via a similar conformation, we designed and synthesized a series of analogs in which the ketoamide group is replaced by an isosteric sulfonamide group. The most potent of these analogs, 14i, demonstrated antiviral potency comparable to 26 in the M33 pseudotyped antiviral assay. Flexible overlay calculations of a ketoamide inhibitor with a sulfonamide inhibitor revealed a single conformation of each that gave significantly better overlap of key pharmacophore features than other conformations and thus suggest a possible binding conformation for each class.