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Biomedical subjects

E J Adams

Publications and source records attributed to E J Adams.

6 recordsLinked to original sources
PubMed1990

A novel series of selective leukotriene antagonists: exploration and optimization of the acidic region in 1,6-disubstituted indoles and indazoles.

A systematic structure-activity exploration of the carboxylic acid region in a series of indole- or indazole-derived leukotriene antagonists 1 led to several discoveries. Use of the 3-methoxy-p-tolyl fragment (illustrated in acid 1) for connecting the indole and the acidic site provides the most potent carboxylic acids 1, tetrazoles 20, and aryl sulfonimides 21. The aryl sulfonimides are 5-500 times more potent (in vitro and/or in vivo) than the corresponding carboxylic acids 1. The o-tolyl sulfonimides such as 114 show greater oral potency than the phenyl sulfonimides at a given level of in vitro activity. Acidic keto sulfone derivatives 10 (Nu = CH-(CO2CH3)SO2Ph) mimic the activity of the sulfonimides.

Animals↗
PubMed1988

Synthesis and pharmacological characterization of a series of leukotriene analogues with antagonist and agonist activities.

The synthesis and biological characterization of a series of novel leukotriene antagonists and agonists are reported. All of these compounds are derivatives of (5S,6R,7Z)-5-hydroxy-6-mercapto-9-phenyl-7-nonenoic acid. One of the more potent compounds is (5S,6R,7Z)-6-[[(4-carboxy-2-methoxyphenyl)methyl]thio]-5-hydroxy-9 -(4- heptylphenyl)-7-nonenoic acid (3f). In vitro evaluation of this compound on guinea pig trachea revealed that it is a competitive antagonist of LTD4 and LTE4 with pKB values of 6.4 and 5.8, respectively. On guinea pig ileum, the pKB values obtained for it with LTD4 and E4 were both 7.2. The selectivity of 3f was shown by its lack of effect on carbachol, histamine, and barium chloride concentration-response curves in guinea pig trachea.

Animals↗
PubMed1986

Chemically stable homocinnamyl analogues of the leukotrienes: synthesis and preliminary biological evaluation.

The synthesis and biological characterization of a series of stable leukotriene analogues (2) are reported. They are derivatives of (5S,6R,7Z)-6-peptidyl-5-hydroxy-9-phenyl-7-nonenoic acid, in which the phenyl group is variously substituted with a heptanyl, 2-heptenyl, or hexanyloxy chain (R1) and the peptide is either glutathionyl, cysteinylglycinyl, or cysteinyl. The most potent agonist is (5S,6R,7Z)-6-S-glutathionyl-5-hydroxy-9-(4-heptanylphenyl)-7 -nonenoic acid. This analogue has an EC50 value of 74.5 nM, in the presence of 1-serine borate (45 mM), on guinea pig tracheal spirals. The agonist activity of the cysteinylglycinyl- and the cysteinyl-substituted analogues was inhibited by FPL-55712. Three of the analogues were weak leukotriene antagonists in vitro on guinea pig tracheal spirals. The most potent of these was (5S,6R,7Z)-6-S-cysteinyl-5-hydroxy-9-(2-heptanylphenyl)-7-++ +nonenoic acid. At 10 microM, this analogue inhibited by 28% the contraction induced by 8 nM LTE4.

Aminopeptidases↗
PubMed1986

Chrysiasis: the role of sun exposure in dermal hyperpigmentation secondary to gold therapy.

To investigate the role of sun exposure in the pathophysiology of chrysiasis, we studied 10 Caucasian female patients with rheumatoid arthritis: 4 with clinically apparent chrysiasis and 6 without apparent pigmentation. Three patients without chrysiasis had received over 4 g of gold and 3 less than one g. The mean melanin score, determined by histological examination of sun exposed and nonsun exposed skin, was significantly higher in the sun exposed skin of the chrysiasis and high dose controls than low dose controls (p less than .05). Concentration of gold measured semiquantitatively by transmission electron microscopy and quantitatively by atomic absorption showed increased gold concentration in sun exposed when compared to nonsun exposed skin of chrysiasis and high dose controls (p = .26). Low dose controls had no gold demonstrated by either method. Our results suggest that gold deposition in the dermis stimulates melain production and that melanin is important in hyperpigmentation of chrysiasis. Furthermore ultraviolet light may induce preferential uptake of gold by the skin.

Arthritis, Rheumatoid↗