Biomedical subjects

E W Badger

Publications and source records attributed to E W Badger.

6 recordsLinked to original sources

PubMed1989

Host-enhanced chemical indexing in technical databases.

Many files that index engineering, physics, or other technical literature contain references to chemical compounds. Complex chemical formulas in the title or abstract often contain special characters, for example, (,), [,], +, -, degrees, and %. Upper and lower case letters often are also included. A search of these formulas and symbols in the basic index is next to impossible because the terms in this field are usually parsed to all alphanumeric characters without sensitivity to case. It is possible for an online host to use a character-recognition algorithm to scan the title and abstract data for special characters or character strings and place them in a separate index field when such files are loaded. Such an algorithm has been designed by Fachinformationszentrun Energie, Physik, Mathematik GmbH in Karlsruhe, West Germany (FIZ Karlsruhe), the European service center of STN International, the scientific and technical information network. This algorithm recognizes and analyzes chemical formulas, material descriptions, alloys, and eutectic systems as well as nuclear reactions and dopings that appear in the title, abstract, or other fields. These character strings are converted into a standardized form and placed in a new field (the element terms field) which is supplied by the online host during the loading process. A checklist of allowed terms (symbols and chemical formulas) is used to prevent irrelevant terms from being mistaken for legitimate chemical symbols. For instance, the algorithm can recognize that CPU (central processing unit) is not a legitimate chemical formula. It is easy to demonstrate the utility this additional index supplies.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstracting and Indexing↗

PubMed1988

2-(2-Aryl-2-oxoethylidene)-1,2,3,4-tetrahydropyridines. Novel isomers of 1,4-dihydropyridine calcium channel blockers.

The title compounds are novel double bond isomers of 1,4-dihydropyridine-type calcium channel blockers (CCB). These derivatives were prepared by using the Hantzsch dihydropyridine synthesis. The assignment of structure was based on spectroscopic data and a regiochemically unambiguous synthesis. Several of the analogues inhibited [3H]nitrendipine binding with IC50 values as low as 25 nM. By comparison, nifedipine, a clinically useful 1,4-dihydropyridine CCB, inhibits [3H]nitrendipine binding with an IC50 of 1.6 nM. In the Langendorff rat heart preparation, treatment with the more potent derivatives produced marked dose-related increases in coronary flow with little or no effect on heart rate or contractility, except at the highest concentrations tested. The selectivity for vascular versus cardiac effects was similar to that of nifedipine, i.e., the concentration producing vasodilation was approximately 2 orders of magnitude lower than the concentration eliciting cardiodepression. These novel isomers extend the structure-activity relationships for calcium channel blockers into a series closely related to the 1,4-dihydropyridines.

Animals↗

PubMed1987

Binding of the A1-selective adenosine antagonist 8-cyclopentyl-1,3-dipropylxanthine to rat brain membranes.

8-Cyclopentyl-1,3-dipropylxanthine (PD 116,948) is a very potent, very A1-selective adenosine antagonist, with a Ki of 0.46 nM in 3H-CHA binding to A1 receptors in rat whole brain membranes and 340 nM in 3H-NECA binding to A2 receptors in rat striatal membranes. Its 740-fold A1-selectivity is the highest reported for an adenosine antagonist. 3H-PD 116,948 (117 Ci/mmol) was prepared by reduction of the diallyl analog. 3H-PD 116,948 bound to a single site in rat whole brain membranes, with a Bmax of 46 pmol/g wet weight and Kd of 0.42 nM. Nonspecific binding was extremely low, amounting to about 3% of total binding under standard conditions and less than 1% when higher tissue concentrations were used. Affinities of compounds for inhibition of 3H-PD 116,948 binding were highly consistent with an A1 adenosine receptor. Antagonists were equally potent in 3H-PD 116,948 binding and in 3H-CHA binding, while agonists were consistently about 12-fold more potent in 3H-CHA binding. Hill coefficients were 1.0 for antagonists and about 0.65 for agonists. 3H-PD 116,948 should be a useful antagonist ligand for adenosine A1 receptors.

Adenosine↗

PubMed1987

PD 115,199: an antagonist ligand for adenosine A2 receptors.

PD 115,199, N-[2-(dimethylamino)ethyl]-N-methyl-4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3- dipropyl-1H-purin-8-yl)benzenesulfonamide, was found to have high affinity for the A2 adenosine receptor labeled by 3H-NECA in rat striatal membranes (Ki 15.5 nM). Unlike other potent adenosine antagonists, which always showed some degree of selectivity for the A1 receptor, PD 115,199 had equal affinity at A1 and A2 receptors (Ki in 3H-CHA binding to A1 receptors 13.9 nM). 3H-PD 115,199 (126 Ci/mmol) was prepared by reduction of the diallyl analog, and binding experiments were performed with 0.5 nM 3H-PD 115,199 at 25 degrees C in rat striatal membranes. By nonlinear least-squares analysis of the concentration-inhibition curve for the highly A1-selective adenosine antagonist PD 116,948 (8-cyclopentyl-1,3-dipropylxanthine), it could be demonstrated that about 11% of specific 3H-PD 115,199 binding was to A1 receptors, and the remainder to A2 receptors. A 20 nM concentration of PD 116,948 was included in subsequent experiments to eliminate the A1 component of binding. The remaining binding had a Kd of 2.6 nM and Bmax of 56 pmol/g wet weight. Specific binding was about 79% of total binding. Affinities of compounds in the 3H-PD 115,199 assay were consistent with binding to a high-affinity A2 receptor: antagonists were consistently about three times more potent in 3H-PD 115,199 binding than in 3H-NECA binding, whereas agonists were consistently about fivefold less potent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Ribose-modified adenosine analogues as adenosine receptor agonists.

Analogues of the potent adenosine receptor agonist (R)-N-(1-methyl-2-phenylethyl)adenosine (R-PIA), modified at N9, were prepared and evaluated for adenosine A1 and A2 receptor binding and in vivo central nervous system and cardiovascular effects. The modifications at N9 include deoxy sugars, 5'-substituted-5'-deoxyriboses, non-ribose sugars, sugar ring homologues, and acyclic sugar analogues. Most of the derivatives have poor affinity for adenosine receptors. Only minor modifications at C5' and C3' maintain potent binding. In general, those derivatives exhibiting in vivo behavioral or cardiovascular effects also have the highest affinity for adenosine receptors.

Adenosine↗

PubMed1985

Synthesis of xanthines as adenosine antagonists, a practical quantitative structure-activity relationship application.

A set of 56 8-phenylxanthines, previously tested for adenosine antagonism (adenosine A1 receptor affinity), was analyzed by quantitative structure-activity relationship (QSAR) techniques. The resulting QSAR revealed that (1) the most potent receptor binders had already been made in this series and thus suggested the termination of synthesis of compounds with additional phenyl substituents to increase potency and (2) potency was much more strongly affected by changes in ortho than para phenyl substitution. On the basis of this study, an additional 20 compounds were synthesized that contained primarily para substituents designed to increase aqueous solubility. High potency was maintained among the resulting sulfonamide derivatives (as predicted by the QSAR), and aqueous solubility was dramatically increased. Furthermore, in vitro antagonism of an adenosine receptor mediated physiological effect was demonstrated.

Adenosine↗