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Biomedical subjects

L S Watson

Publications and source records attributed to L S Watson.

At least 19 recordsLinked to original sources
PubMed1991

Hydrogel contact lens dehydration rates determined by thermogravimetric analysis.

Because many practitioners believe that the on-eye drying of contact lenses is a source of patient discomfort, we examined the relative dehydration rates of a variety of hydrogel contact lenses. Lens dehydration rates were determined by thermogravimetric analysis at 35[degrees]C. Using the FDA classification scheme for hydrogel lenses, we found that dehydration rates were as follows: group 4 greater than group 2 greater than group 3 greater than group 1. Within groups there was considerable variability in the rates at which lenses dehydrated. For lenses of the same type, we found a near-linear relationship between increasing lens power (which is closely related to center thickness) and decreasing rates of dehydration.

Contact Lenses, Hydrophilic↗
PubMed1983

2-(Aminomethyl)phenols, a new class of saluretic agents. 5. Fused-ring analogues.

A number of bicyclic ring-fused analogues of 2-(aminomethyl)phenol were synthesized and tested orally in rats and intravenously in dogs for saluretic and diuretic effects. Of the 15 alicylic, aromatic, and heterocyclic ring-fused compounds tested, only 2-(aminomethyl)-4-chloro-1-naphthalenol hydrochloride (2) and 7-(aminomethyl)-6-hydroxy-5,8-dimethyl-1,2,3,4-tetrahydronaphthalene hydrochloride (6) displayed a high order of activity.

Amines↗
PubMed1983

2-(Aminomethyl)phenols, a new class of saluretic agents. 6. Effects of N,O-spiroannulation and subsequent quaternization.

The synthesis of a number of 3,4-dihydrospiro-2H-1,3-benzoxazines and their corresponding benzoxazinium salts are reported. The saluretic effects displayed by these N,O-spiroannulated 2-(aminomethyl)phenols appear to be, in part, inversely related to their respective in vivo rates of hydrolysis. Good antihypertensive effects are found only in spirobenzoxazinium 22. Thus, a combination of spiroannulation and quaternization on 2 to produce 22 leads to a loss of saluretic effects with maintenance of antihypertensive effects and, thereby, serves to separate these pharmacological properties.

Amines↗
PubMed1982

2-(Aminomethyl)phenols, a new class of saluretic agents. 4. Effects of oxygen and/or nitrogen substitution.

A series of oxygen and/or nitrogen substituted 2-(aminomethyl)phenols was synthesized and tested orally in rats for saluretic and diuretic effects. Intravenous dog data are included as supplementary material to demonstrate diuretic responses, or lack thereof, in a second species. In general, substitution on nitrogen with groups other than lower alkyl or substitution on nitrogen and/or oxygen with groups resistant to hydrolysis substantially diminished or ablated saluretic effects.

Animals↗
PubMed1981

(Acylaryloxy)acetic acid diuretics. 3. 2,3-Dihydro-5-acyl-2-benzofurancarboxylic acids, a new class of uricosuric diuretics.

The discovery that dihydroethacrynic acid and other (4-acylphenoxy)acetic acids possessed modest but significant uricosuric and diuretic activity prompted our investigation of the related 2,3-dihydro-5-acyl-2-bensofurancarboxylic acids. Synthetic routes to a number of these compounds are presented along with the structure-activity relationships generated from studies in rats, dogs, and chimpanzee. Examination of the enantiomers of 6,7-dichloro-2,3-dihydro-5-(2-thienylcarbonyl)-2-benzofurancarboxylic acid (10c) in the chimpanzee revealed that all diuretic and saluretic activity is due to the (+) enantiomer 10d, while the (-) enantiomer 10e is responsible for all of the uricosuric activity. X-ray analysis showed that the (-) enantiomer 10e possesses the 2R configuration.

Animals↗
PubMed1981

2-(Aminomethyl)phenols, a new class of saluretic agents. 3. Effects of functional group reorientation and modification.

A series of modified 2-(aminomethyl)phenols was synthesized and tested orally in rats for saluretic and diuretic effects. Intravenous dog data are included as supplementary material to show that the diuretic responses, or lack thereof, may be obtained in a second species. Reorientation of the 2-(aminomethyl) group either meta or para to the hydroxyl substituent resulted in loss of diuretic effects. Similarly, replacement of either the phenolic hydroxyl or the aminomethyl group with other functional moieties substantially diminished saluretic effects.

Amines↗
PubMed1980

2-(Aminomethyl)phenols, a new class of saluretic agents. 1. Effects of nuclear substitution.

A series of 2-(aminomethyl)phenols was synthesized and tested in rats and dogs for saluretic and diuretic activity. A number of these compounds exhibit a high order of activity on iv or po administration. The most active compounds belong to a subseries of 4-alkyl-6-halo derivatives of which 2, 2-(aminomethyl)-4-(1,1-dimethylethyl)-6-iodophenol, is the most active. Compound 2 also possesses significant antihypertensive activity, an adjunctive pharmacological parameter which distinguishes 2 from the other compounds prepared in this series. In addition, 2 displays both topical saluretic and antiinflammatory activities.

Administration, Oral↗
PubMed1980

Diuretic and uricosuric activity of 6,7-dichloro-2,3-dihydro-5-(2-thienylcarbonyl)benzofuran-2-carboxylic acid and stereoisomers in chimpanzee, dog and rat.

The racemate and the d-isomer of 6,7-dichloro-2,3-dihydro-5-(2-thienylcarbonyl)benzofuran-2-carboxylic acid exhibited diuretic activity in the chimpanzee, dog and rat. In the chimpanzee, the diuresis and natriuresis presumably resulted from a site of action in the thick ascending limb of Henle's loop. The l-isomer was uricosuric but devoid of any diuretic action in the chimpanzee and similarly was not diuretic in the dog and rat. Various proportions of the two isomers were tested in the chimpanzee in an attempt to produce an optimal diuretic and uricosuric profile. It was concluded that the racemic mixture, under these experimental conditions, was responsible for the most effective overall response. This is apparently the first time in which there is a distinct separation of diuretic and uricosuric actions in the enantiomers of a racemic diuretic uricosuric agent.

Animals↗
PubMed1979

Antihypertensive and other cardiovascular effects of 2-(3-pyridyl)- and 2-(4-pyridyl)-4-trifluoromethylimidazoles.

2 new 4-trifluoromethylimidazole derivatives were found which lowered mean arterial pressure in renal and spontaneously hypertensive (SH) rats by the oral route. In SH rats, compounds A and B were 0.1 and 0.3 times, respectively, as potent as hydralazine. No tolerance development was observed in SH rats with either compound over a 1-week period. In anesthetized dogs, both compounds lowered arterial pressure and peripheral vascular resistance but increased cardiac output. By intraarterial administration, both compounds increased femoral arterial blood flow. These findings represent discovery of a new class of vasodilator durgs.

Animals↗
PubMed1979

Diuretic and antihypertensive effects of 2-aminoethyl-4-(1,1-dimethylethyl)-6-iodophenol hydrochloride (MK-447).

2-Aminomethyl-4-(1,1-dimethylethyl)-6-iodophenol hydrochloride or MK-447, is a chemically novel diuretic agent which produced diuretic and saluretic effects in rats, dogs and chimpanzees. At doses ranging from 0.1 to 10 mg/kg p.o. (0.32-32 mumol/kg) MK-447 was more effective then furosemide at the same or higher doses in increasing the excretion of Na+, K+ and Cl- in rats and dogs. At single oral doses, MK-447 had antihypertensive activity in spontaneously hypertensive rats and renal hypertensive dogs. Other diuretics are known to lower arterial pressure in these models only by repeated administration. The antihypertensive and diuretic effects of MK-447 in spontaneously hypertensive rats were reduced by indomethacin.

Animals↗
PubMed1978

(Acylaryloxy)acetic acid diuretics. 2. (2-Alkyl-2-aryl-1-oxo-5-indanyloxy)acetic acids.

The introduction of an aryl group at the 2 position of the uricosuric diuretics, (1-oxo-2-alkyl-5-indanyloxy)acetic acids, provided compounds with markedly increased potency over their monosubstituted precursors. These compounds were synthesized either by arylation of the corresponding 2-alkyl-5-methoxy-1-indanones with diaryliodonium salts or by alkylation of the 2-aryl-5-methoxy-1-indanones which were cleaved to the corresponding phenols and then converted to the desired oxyacetic acids. Systematic structural variation of the 2-arylindanyloxyacetic acids provided aryl-substituted compounds with varying degrees of uricosuric and diuretic activity.

Acetates↗
PubMed1976

(Vinylaryloxy)acetic acids. A new class of diuretic agents. 2. (4-(3-Oxo-1-alkenyl)phenoxy)acetic acids.

A series of (E)-[4-(3-oxo-1-alkenyl)phenoxy]acetic acids was synthesized and tested in dogs for saluretic and diuretic properties. Several compounds exhibited noteworthy activity, e.g., (E)-[2,3-dichloro-4-(3-oxo-1-butenyl)phenoxy]acetic acid (3a). While possessing only half of the dose potency of ethacrynic acid (2), the active compounds act similarly to this diuretic in causing a prompt increase in the excretion of water and in the excretion of sodium and chloride ions in approximately equimolar amounts. Potassium ion excretion is increased but less markedly than sodium excretion.

Acetates↗
PubMed1976

(Vinylaryloxy)acetic acids. A new class of diuretic agents. 3. ((2-Nitro-1-alkenyl)aryloxy)acetic acids.

A series of [(2-nitro-1-alkenyl)aryloxy]acetic acids was synthesized and tested in dogs for saluretic and diuretic activity. A number of these compounds exhibit a high order of activity on iv or po administration; representative of these is (E)-[2,3-dichloro-4-(2-nitropropenyl)phenoxy]acetic acid (5). The most highly active compounds are qualitatively similar in action to [2,3-dichloro-4-(2-methylenebutyryl)phenoxylacetic acid (ethacrynic acid) in causing a prompt increase in the excretion of water and of sodium and chloride ions in approximately equimolar amounts but are three to five times as potent. Potassium ion excretion is increased but less markedly than sodium excretion.

Acetates↗
PubMed1976

(Vinylaryloxy)acetic acids. A new class of diuretic agents. 4. Various ((2-substituted and 2,2-disubstituted vinyl)aryloxy)acetic acids.

A variety of [(2-substituted and 2,2-disubstituted vinyl)aryloxy]acetic acids was synthesized in which the substituents were primarily electron-withdrawing groups. These compounds were tested in dogs for their saluretic and diuretic properties. Many of the compounds exhibited significant activity; however, they were generally less potent than those reported in the three earlier papers in this series.

Acetates↗