Biomedical subjects

A E Jacobson

Publications and source records attributed to A E Jacobson.

At least 199 records · Page 11Linked to original sources

PubMed1977

Potential long acting opiate antagonists: preparation, pharmacological activity, and opiate-receptor binding of N-substituted 2'-hydroxy-5-methyl-9 alpha-propyl-6,7-benzomorphans.

A homologous series of N-substituted 2'-hydroxy-5-methyl-9 alpha-propyl-6,7-benzomorphans (hydrogen to octyl inclusive, allyl, and cyclopropylmethyl) was prepared. In contradistinction to the normetazocine, normorphine, and (-)-3-hydroxymorphinan series, the N-pentyl and N-hexyl derivatives do not have the analgesic potency of the parent N-methyl compound; instead, they are narcotic antagonists with a long duration of action. All of the N-substituted 9 alpha-propylbenzomorphans, except for methyl, heptyl, and octyl, have antagonist activity. The receptor binding constants of the N-alkyl compounds are uniformly two- to threefold lower than those of the N-substituted normetazocines.

Analgesics↗

PubMed1977

Chemistry and pharmacology of homologs of 6-acetyl-and 3,6-diacetylmorphine.

3,6-Diformyl- and 3,6-dipropanoylmorphine and 6-formyl- and 6-propanoylmorphine were prepared to obtain longer acting, heroin-like compounds. The 6-acylated compounds were more potent than heroin subcutaneously and were orally effective, and their duration of action was at least two to three times greater than that of heroin in monkey species.

Acetylation↗

PubMed1977

N-(2,4,5-Trihydroxyphenehtyl)normetazocine, a potential irreversible inhibitor of the narcotic receptor.

The reaction of N-2,4,5-tribenzyloxyphenyl)ethyl methanesulfonate, prepared in a seven-step sequence, with normetazocine followed by hydrogenolysis of the benzyloxy-protecting groups, gave N-(2,4,5-trihydroxyphenethyl)normetazocine. This compound was prepared to study the effect of a narcotic analgesic containing a functional group which could be activated in situ to a moiety potentially capable of reacting irreversibly with the narcotic receptor. This 6-hydroxydopamin derivative of normetazocine did not prove to be a useful affinity label. Its low toxicity could indicate the necessity for the formation of an aminochrome system for the expression of toxicity by 6-hydroxydopamine.

Adenylyl Cyclases↗

PubMed1976

Alpha-and beta-halomorphides: stereochemistry, analgesic potency, toxicity, and interaction with narcotic receptors in vitro.

The configuration of the halogen on the C-ring of several alpha- and beta-halomorphides was determined by NMR. The analgesic potencies of these halomorphides and their interactions with narcotic receptors in a rat brain homogenate were measured, as was the toxicity of the alpha- and beta-chloromorphides. The halomorphides were examined as possible irreversible binders to the narcotic receptor.

Analgesics↗

PubMed1976

Optical resolution of (+/-)-2,5-dimethyl-2'-hydroxy-9alpha- and -9beta-propyl-6,7-benzomorphans and their pharmacological properties.

The levo and dextro isomers of 2,5-dimethyl-2'-hydroxy-9alpha- and -9beta-propyl-6,7-benzomorphans have been prepared. The analgesic potency and physical dependence capacity of the optical isomers and their racemic parents were determined. The 9alpha-propyl levo isomer was analgesically equipotent with morphine; the 9beta-propyl levo isomer was considerably more potent subcutaneously and equipotent orally. None of the optical isomers suppressed the withdrawal syndrome; the 9beta-propyl levo isomer exacerbated the withdrawal syndrome.

Analgesics↗

PubMed1975

Synthesis and analgesic activities of 2,5-dimethyl-2'-hydroxy-9alpha- and -beta-propyl-6,7-benzomorphans.

The 2,5-dimethyl-2'-hydroxy-9alpha- and-beta-propyl-6,7-benzomorphans were synthesized from 4-methyl-3-propylpyridine in five steps, in an overall yield of 14 and 5%, respectively. The required 4-methyl-3-propylpyridine was prepared in an overally yield of 34% by a four-step sequence. The benzomorphans were about as potent as, or more potent than, morphine in vivo.

Analgesics↗

PubMed1975

Preparation and analgesic activity of 3,6-diacetylnormorphine and 6-acetylnormorphine.

3,6-Diacetylnormorphine (norheroin) and 6-acetylnormorphine have been prepared in excellent yield through the 3,N-bis(tert-butoxycarbonyl) derivative of normorphine via acetylation and selective removal of protecting groups. This general procedure would be applicable to the preparation of various 3,6-diesters or 6-monoesters of normorphine. The analgesic potency of norheroin was found to be the same as that of 6-acetylnormorphine, about 0.05 that of heroin. The onset, peak, and duration of action of these compounds were nearly identical and comparable with morphine.

Analgesics↗

PubMed1974