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T D Nelson

Publications and source records attributed to T D Nelson.

5 recordsLinked to original sources
PubMed1994

Synthesis and opioid receptor affinity of a series of aralkyl ethers of 6 alpha- and 6 beta-naltrexol.

A series of 6-O-ethers of 6 beta- and 6 alpha-naltrexol (6 and 7) were prepared to examine the effect of large aralkyl groups on affinity of the ligands for opioid receptors. The affinities of the 6 beta- and 6 alpha-O-ether with benzyl, biphenylmethyl, 1- and 2-naphthylmethyl, and 9-anthracylmethyl groups were determined. Preparation of the ligands was accomplished from suitably 3-O-protected derivatives of 6 and 7 by phase transfer catalyzed alkylation using aralkyl halides, followed by deprotection. Both 3-O-trityl and -benzyl protecting groups were used. In radioligand displacement assays, compounds from the 6 alpha-O ether series had higher affinity than the analogous diastereomers in the 6 beta-O series, with few exceptions. In the 6 alpha-O series, the benzyl ether (29) and the biphenylmethyl ether (30) had the highest affinity, similar to naltrexone. In the 6 beta-O series, the benzyl ether had the highest affinity. The larger aralkyl ethers had slightly less affinity. Large lipophilic 6 beta-O- and 6 alpha- O-aralkyl groups are readily accommodated in the drug-receptor interaction.

Alkylation↗
PubMed1992

New vitamin D3 derivatives with unexpected antiproliferative activity: 1-(hydroxymethyl)-25-hydroxyvitamin D3 homologs.

Surprisingly, both of the synthetic 1-(hydroxymethyl)-25-hydroxyvitamin D3 diastereomers (-)-2 and (+)-3 retained the antiproliferative activity of natural calcitriol in murine keratinocytes. Preliminary studies indicated, however, that both of these synthetic diastereomers were less than 0.1% as effective as calcitriol for binding to the 1,25-(OH)2-D3 receptor and that they were less than 0.1% as potent as calcitriol for calbindin-D28K induction in organ-cultured embryonic chick duodenum. 1-(Hydroxymethyl)-25-hydroxyvitamin D3 homologs (-)-2 and (+)-3 were synthesized in a convergent manner by combining enantiomerically pure C,D-ring ketone 12 with highly enantiomerically enriched A-ring phosphine oxides (-)-11a and (+)-11b. These A-ring chirons were prepared starting from thermal [2 + 4] cycloaddition of 3-bromo-2-pyrone and acrolein.

Animals↗
PubMed1978

Fixed-interval matching-to-sample: intermatching time and intermatching error runs.

Four pigeons were trained on a matching-to-sample task in which reinforcers followed either the first matching response (fixed interval) or the fifth matching response (tandem fixed-interval fixed-ratio) that occurred 80 seconds or longer after the last reinforcement. Relative frequency distributions of the matching-to-sample responses that concluded intermatching times and runs of mismatches (intermatching error runs) were computed for the final matching responses directly followed by grain access and also for the three matching responses immediately preceding the final match. Comparison of these two distributions showed that the fixed-interval schedule arranged for the preferential reinforcement of matches concluding relatively extended intermatching times and runs of mismatches. Differences in matching accuracy and rate during the fixed interval, compared to the tandem fixed-interval fixed-ratio, suggested that reinforcers following matches concluding various intermatching times and runs of mismatches influenced the rate and accuracy of the last few matches before grain access, but did not control rate and accuracy throughout the entire fixed-interval period.

Journal Article↗
PubMed1978

Local response-rate constancy on concurrent variable-interval schedules of reinforcement.

Concurrent variable-interval schedules were arranged with a main key that alternated in color and schedule assignment, along with a changeover key on which a small fixed ratio was required to changeover. Acceptable matching was observed with pigeons in two replications, but there was a tendency toward overmatching. Local response rates were found to differ for unequal schedules of a concurrent pair: local response rate was greater for the variable-interval schedule with the smaller average interreinforcement interval, but qualifications based on an interresponse-time analysis were discussed. In a second experiment, two 3-minute variable-interval schedules were arranged concurrently, and the experimental variable was the changeover procedure: either a changeover delay was incurred by each changeover or a small fixed ratio on a changeover key was required to complete a changeover. Changeover delays of 2 and 5 seconds were compared with a fixed-ratio changeover of five responses. The response output on the main key (associated with the variable-interval schedules) was greater when a changeover delay was arranged than when a fixed ratio was required to changeover. A detailed analysis of stripchart records showed that a 2-second delay generated an increased response rate for 3 seconds after a changeover, while the fixed-ratio requirement generated an increased rate during the first second only, followed by a depressed response rate for 2 seconds.

Journal Article↗