Oscillations in some linear free energy relationships derived from partition coefficients of phenols between octanol and water.

In the partition of some resorcinol alkyl ethers between water and 1-octanol, the values of delta Gtrs do not increase in a regular way. Odd and even chain alkyl compounds show different, regular increases in delta Gtrs for addition of each methylene group. The unrecognized occurrence of this phenomenon in earlier data is pointed out, and its possible significance in medicinal chemistry is discussed.

Neodymium-YAG transscleral cyclocoagulation in rabbit eyes.

Transscleral ruby cyclocoagulation has been successfully used to lower intraocular pressure. The recent commercial availability of Nd-YAG lasers with a thermal mode provides a possible alternative by which to perform this procedure. We treated one eye of seven pigmented rabbits using the thermal mode of the Nd-YAG laser. The intraocular pressures were followed up for three months. The treated eyes had significantly lower mean intraocular pressures were followed up for three months. The treated eyes had significantly lower mean intraocular pressures than the untreated contralateral eyes (p less than 0.001). Moreover, the decrease was sustained over the three-month duration of the study. Pathological examination revealed very selective destruction of the ciliary processes, with sparing of the overlying ciliary muscle, sclera, and conjunctiva. The potential value of this mode of therapy for use in patients with glaucoma is discussed.

Quantitative structure-activity relationships: the Van't Hoff heats of transfer of resorcinol monoethers from water to n-octanol.

The partition coefficients of resorcinol and some resorcinol monoalkyl-ethers from water to n-octanol have been measured as a function of temperature. These data are used to evaluate delta G, delta H and delta S for the solute transfer process. The data suggest direct calorimetric measurement of these parameters should be performed. Correlation with calorimetrically determined 'biological response' will permit a more detailed and precise commentary upon the quantitative structure-activity relationships for these compounds.

Enthalpies of solution of a series of m-alkoxy phenols in water, n-octanol and water-n-octanol mutually saturated: derivation of the thermodynamic parameters for solute transfer between these solvents.

Enthalpies of solution in both water and n-octanol have been determined for a series of phenols, in a microcalorimeter modified for titration. The thermodynamic data for solution in n-octanol and in water, as well as for transfer between the two, have been calculated from the free energies of transfer, based upon partition coefficients, and the free energies of solution, based upon solubility data. The results are discussed in terms of solute-solvent interactions in both phases and are used to assess, critically, the use of n-octanol as lipid-like solvent in QSAR studies.

The measurement of phenol coefficients by flow microcalorimetry.

Microcalorimetric bioassay procedures have been applied to the determination of phenol coefficients and dilution coefficients. The derived values are compared with those from a standard AOAC test procedure. This microcalorimetric results indicate close agreement with AOAC values, good reproducibility (+/- 2%), rapidity (30 min per test), potential for automation and the determination of in-use dilutions of disinfectants.

A thermodynamic analysis of the Collander equation and establishment of a reference solvent for use in drug partitioning studies.

A thermodynamic analysis of the Collander equation, ln PI = a + b ln PII (I and II refer to two different partitioning systems with partition coefficients PI and PII, respectively), is given and applied to three forms of correlation. The intercept, a, is shown to have no general fundamental significance whereas the slope, b is shown to reflect differences in non-aqueous solvent properties; b is also shown to be of use in scaling solvent behaviour to select solvents which closely represent biological membrane properties for use in partitioning studies. Laboratory and literature data are subjected to the analysis.

The metabolism of acetamidothiazoles in the rat. 2-Acetamido-, 2-acetamido-4-methyl- and 2-acetamido-4-phenyl-thiazole.

The metabolism of some anti-inflammatory acetamidothiazoles was studied in the rat. The main metabolites were the corresponding acetylthiohydantoic acids, produced by fission of the thiazole ring. Minor metabolites arising from oxidation of the methyl or phenyl substituents were also identified. The structures of metabolites were established spectroscopically (u.v., i.r., n.m.r. and mass spectroscopy) and by identification with authentic specimens. The excretion of the original compounds and of metabolites, labelled with (14)C is also reported.

The metabolism of acetamidothiazoles in the rat. 2-acetamido-4-chloromethylthiazole.

2-Acetamido-4-chloromethylthiazole is metabolized in the rat to (2-acetamido-4-thiazolylmethyl)mercapturic acid and 2-acetamidothiazole-4-carboxylic acid. 2-Acetamido-4-methylthiomethylthiazole and the corresponding sulphoxide and sulphone are also produced as minor metabolites. The identification of the metabolites is described and their formation investigated. Quantitative results on the excretion of the metabolites labelled with (14)C are reported.

The synthesis of some bridgehead N,O-heterocycles of biological interest.

The preparation of 5-aryl-6-oxa-1-azabicyclo[3,3,0]octanes, 6-aryl-5-oxa-1-azabicyclo[4,3,0]nonanes and 7-aryl-6-oxa-1-azabicyclo[5,3,0]decanes from the corresponding substituted omega-chlorobutyrophenones and aminoalcohols is described; and the ring opening reactions are studied. A preliminary biologic activity study has also been conducted, and demonstrated that the 5-(2,5-dimethyl)phenyl-6-oxa-1-azabicyclo[3,3,0]octane possesses antiinflammatory activity.

Neodymium: YAG transscleral cyclocoagulation in human eyes.

Transscleral neodymium: YAG (Nd:YAG) cyclocoagulation has been successfully used to lower intraocular pressure (IOP) in rabbits. The authors treated 24 patients with uncontrolled glaucoma using the thermal mode of the Nd:YAG laser. The patients were followed for a mean of 8.8 months. A total of 62.5% of treated eyes achieved an IOP on last follow-up of 25 mmHg or less. The mean pretreatment pressure was 47.2 mmHg and the mean posttreatment pressure was 25.7 mmHg (P = 0.009). The complications and potential clinical usefulness of this mode of therapy are discussed.