A series of C-1 oxazole isosteres of pseudomonic acid A (mupirocin) bearing a nitroheterocycle have been synthesized, and significant differences in both spectrum of activity and potency were found between these derivatives and mupirocin. Additionally, the antibacterial potency of two members of this class of compounds against mupirocin-resistant staphylococci could not be accounted for solely by inhibition of the target enzyme isoleucyl-tRNA synthetase (IRS), indicating an additional mode of action. The most potent compound, the nitrofuran 3f (SB 205952), was the most electron affinic derivative prepared and was transformed by NAD(P)H-dependent bacterial reductases at a rate similar to that for nitrofurantoin. The second mode of action of this compound may therefore arise from its reduction to a species with cellular targets other than IRS. In in vivo studies, 3f was shown to be a very effective agent by both the subcutaneous and oral routes of administration.

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Semisynthetic analogues of pseudomonic acid A have been prepared containing a heterocyclyl substituted oxazole. Derivatives in which the heterocycle was thiophene, furan, pyridine, or isoxazole showed good antibacterial potency and were further evaluated in vivo. Both pharmacokinetic parameters and oral activity against an experimental intraperitoneal sepsis were superior to results obtained from previously described pseudomonic acid A derivatives.

Earlier reports from these laboratories outlined the preparationx) and biological properties2>3) of 6a-formamido penicillins.The catecholic acylureido derivative BRL 36650 (1) was the most potent, especially against Pseudomonas aeruginosa strains.We nowreport on analogues of 1 which either retain a catechol or dihydroxyphenyl unit or contain various catechol isosteres.

Cyclohexanones react rapidly at or below room temperature with Ph3P and XCCl3 (X = Br or Cl) in acetonitrile to give 1,1-dichloromethylene compounds in high yield; some α-methoxyimino β-(1,1-dichloro)methylene esters have been similarly prepared.

We studied 48 prepubertal boys with cryptorchidism between 1 year 3 months and 11 years old who were treated with buserelin every other day for 6 months. Urinary luteinizing and follicle-stimulating hormones, and testosterone remained unchanged during the entire treatment period. In boys older than 7 years a slight but significant increase in testosterone was noted in the first morning voided urine at the end of treatment. Testicular biopsies were obtained at orchiopexy in all patients in whom testicular descent was not complete (83 per cent). A significant increase in the number of germ cells was observed in patients with unilateral and those with bilateral cryptorchidism, indicating that 6 months of buserelin therapy improved the fertility status even when testes were in an undescended position during treatment.

A versatile and convenient synthesis of 4-substituted vinyl glycines, employing novel phosphorane and phosphonate intermediates is reported.

In a collaborative study, 48 prepubertal boys with undescended testes ranging in age from 15 months to 11 years were treated with low-dose intranasal buserelin following an every-other-day programme for a period of 6 months. Urinary LH, FSH, and testosterone were not altered during the treatment period. Boys over 7 years of age experienced a slight but significant rise in testosterone at the end of treatment. Testicular descent was achieved in only 17% of boys. In the remainder, bilateral testicular biopsies were obtained during orchiopexy. Grouped analysis showed a significant increase in the number of germ cells per tubule in both unilateral and bilateral cryptorchid boys, suggesting that buserelin treatment of the testis in a cryptorchid position is capable of improving fertility potential. If time-matched controls are compared to treated boys of the same age, again a significant difference is observed indicating that buserelin treatment does increase the germ cell count.

The wave form of all atmospherics received at night from sources within 2000 km. can be accurately described as a ground pulse followed by a series of sky pulses produced by successive reflexions between the ionosphere and the earth, thirty such reflexions being frequently recorded. The time separation between the peaks of these pulses is determined by the distance travelled and the height of the layer. The primary pulse emitted by the source is usually a single complete oscillation of period ranging from 50 to 400//sec. A t distances greater than 500 km. the ground pulse and the first sky pulse merge owing to the shortness of the time interval between them . Differences of amplitude, form and phase between pulses can arise from differences in angle of emission from the parent lightning channel. The height of the reflecting layer can be determined within ± 1 km. It ranged from 85-5 to 90-5 km. during two winter months, with a mean of 88-0 km. The distances of the sources as found by analysis of the pulse series were corroborated by independent location with cathode-ray direction-finders. The reflexion coefficient of the layer for the pulses of longer period exceeded 0-80. The velocity of the ground pulse where it can be tested is within 0.7 % of that of light.

THE details of the structure of the oscillatory portion of the wave-form of an atmospheric have been the subject of several investigations1. Prof. T. H. Laby and his co-workers of the Australian Radio Research Board have made the remarkable suggestion that the observed complicated structure can be interpreted in terms of a series of reflections from an ionospheric layer of the simpler primary disturbance due to lightning. Their analysis places this height at 59–88 km.