Synthesis and pharmacology of 2-(2-aminoethyl)imidazole (2-isohistamine)

Kornfeld, Edmund C.; Wolf, L. R.; Lin, T. M.; Slater, Irwin H.

doi:10.1021/jm00311a025

Cited by 9 publications

(3 citation statements)

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“…3-(p-Bromobenzyl)-12-hydroxy-d-pilocarpiniumhydroxamic Acid Bromide (25). To a suspension of 0.84 g (0.012 mol) of NH20H-HC1 in 20 ml of absolute EtOH, a solution of NaOEt (3%) was added dropwise up to pH 7.8-8.0 and, after cooling (-5°), the mixture was directly filtered into the precooled solution of 1.84 g (0.004 ml) of 3-(p-bromobenzyl)-d-pilocarpinium bromide1 in 40 ml of EtOH.…”

Section: Methodsmentioning

confidence: 99%

Quaternary pilocarpine derivatives as potential acetylcholine antagonists. 2. Alterations in the lactone and imidazole moieties

Ben-Bassat¹,

Lavie²,

Edery³

et al. 1976

J. Med. Chem.

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In order to investigate the chemical behavior of pilocarpine, as well as the factors which determine its pharmacological activity, systematic and specific structural changes involving the lactone and imidazole moieties have been performed. Series of model compounds with cyclic or open-chain structures and a variety of N-3 bonded chains obtained from previously prepared anticholinergic derivatives of pilocarpine have been synthesized. The changes included N-3 chains of different lengths with an acetylcholine-like structure, the introduction of nucleophilic groups such as ketoxime, hydroxamic, or both at the side chain, or following hydroxylaminolysis of the lactone, respectively. Specific structural alterations could be obtained by reacting with free hydroxylamine under carefully controlled conditions, and the existence of syn and anti isomers was disclosed in certain cases. The new groups in the pilocarpine derivatives influenced their degree of antagonism to acetylcholine. Several compounds displayed some antidotal activity.

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Section: Methodsmentioning

confidence: 99%

Quaternary pilocarpine derivatives as potential acetylcholine antagonists. 2. Alterations in the lactone and imidazole moieties

Ben-Bassat¹,

Lavie²,

Edery³

et al. 1976

J. Med. Chem.

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“…d^d-Dimethylhistamine (24) was prepared as reported by Jonsson.32 a-Methylhistamine (25) was prepared as reported by Alies et al 33 with the exception that the dihydrochloride was characterized. Alternatively, 25 may be prepared from histidine by reduction to histidinol, conversion into abromomethylhistamine, and hydrogenolysis, as described recently by Ison and Casy348 and performed independently in these laboratories by Suschitsky.34b…”

Section: Tpcv = Tv X Pcvmentioning

confidence: 99%

“…The weakly active agonists bearing methyl groups on ring nitrogens (4,13) or side-chain carbon atoms (23)(24)(25) were subsequently tested for H2-receptor antagonist activity against histamine-stimulated gastric acid secretion in the anesthetized rat. 3 The compounds were injected intravenously after a plateau of secretion had been established to an intravenous infusion of histamine.…”

Section: Tpcv = Tv X Pcvmentioning

confidence: 99%

Potential histamine H2-receptor antagonists. 3. Methylhistamines

Gj¹,

Jc²,

Cr³

et al. 1976

J. Med. Chem.

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Syntheses are described for all the mono- and some di- and trimethylhistamines. New methods are given for the known Npi, Ntau-, Nalpha-, 2-, and 4-methylhistamines and for the novel compounds, beta-methyl-, 4,Nalpha-dimethyl-, and 4,Nalpha,Nalpha-trimethylhistamines. Agonist activities are reported for stimulation of histamine H1 (guinea-pig ileum) and H2 (rat gastric acid secretion) receptors. H2-Receptor agonist activities indicate that a methyl group is more readily accommodated at the 4 and Nalpha positions than elsewhere in the histamine molecule and that receptor binding is substantially retained with a methyl substituent in these positions. Thus, for the design of potential antagonists, two sites are identified as being worthwhile exploring for the introduction of lipophilic substituents.

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