Aminoalkyl Derivatives Research Articles

ChemInform Abstract: Substituted 1,3,4‐Thiadiazoles with Anticonvulsant Activity. Part 2. Aminoalkyl Derivatives.

AbstractThe thiadiazoles (I) are prepared from dithioesters via thiohydrazides by known methods.

Iodobolpyramine and other iodinated derivatives as ligands for detecting histamine H 1 receptors

The synthesis is described of potential I-labelled H 1-receptor ligands. Receptor affinity is assessed in vitro from inhibition of histamine-stimulated contraction of guinea pig ileum and/or through binding to guinea pig cerebellar membranes. Direct iodination of mepyramine and of hydroxy analogues of mepyramine and temelastine (SK&F 93944) furnishes derivatives which have lower receptor affinities than the parent compounds. In another approach, novel aminoalkyl derivatives of mepyramine are converted via the [ 125I]Bolton—Hunter reagent into the corresponding 3-(4-hydroxy-5-[ 125I]-iodophenyl)propionamides, each of which is separated chromatographically and its affinity determined by a binding assay. The compound of highest affinity is [ 125I]iodobolpyramine, derived from the aminopentyl analogue, and is among the most potent of known H 1 anti-histamine ligands providing a highly sensitive means of detecting H 1 receptors. A convenient synthesis of [ 125I]iodobolpyramine from bolpyramine and iodo-gen is also described; the compound is purified by TLC and authenticated by HPLC comparison with non-radiolabelled mono- and di-iodinated bolpyramine derivatives. Cyanobutyl-and acetamidopentyl-analogues of mepyramine are also tested as histamine antagonists and structure—activity relationships are described.

Substituted 1,3,4-thiadiazoles with anticonvulsant activity. 2. Aminoalkyl derivatives.

This paper describes the synthesis and pharmacological evaluation of a number evaluation of a number of substituted 1,3,4-thiadiazoles. The first member of the series, 2-(aminomethyl)-5-(2-biphenylyl)-1,3,4-thiadiazole (7) was found to possess potent anticonvulsant properties in rats and mice and compared favorably with the standard anticonvulsant drugs phenytoin, phenobarbital, and carbamazepine in a number of test situations. The potency of compound 7 was maintained on alkylation of the side-chain nitrogen atom; however, aryl substitution or chain lengthening caused a drop in potency. Replacement of the 2-biphenylyl group by phenyl or benzyl also lead to inactive compounds.

Synthesis of pyrrolo[2,1‐c][1,4]benzoxazepines. 1. A novel heterocyclic ring system

AbstractThe synthesis of a novel pyrrolo[2,1‐c][1,4]benzoxazepine ring system (II) by a nucleophilic aromatic fluoride displacement‐cyclization is described. Aminoalkyl derivatives were prepared by either the Mannich reaction, or Vilsmeier formylation to provide the 3‐formyl derivative which was further elaborated.

Aminoalkyl derivatives of 2,4′‐bithiazole‐4‐carboxylic acid, the intercalating part of bleomycin

AbstractThe synthesis of three 2,4′‐bithiazole derivatives related to the antibiotic antitumor bleomycin is reported. These compounds substituted by aminoalkyl chains on 2′ and/or 4‐positions were prepared by the Hantzs synthesis between new thioamides and methyl 2‐(2‐bromoacetyl)thiazole‐4‐carboxylate and will be useful for the study of the intercalative moiety of bleomycin.

Synthesis and anticonvulsant activity of aminoalkyl derivatives of 5-(p-alkoxyphenyl)-5-methylhydantoins

Synthesis and anticonvulsant activity of aminoalkyl derivatives of 5-(p-alkoxyphenyl)-5-methylhydantoins

Synthesis and biological activity of aminoalkyl derivatives of 5-hydroxyindole

Synthesis and biological activity of aminoalkyl derivatives of 5-hydroxyindole

N-(Aminoacyl) and N-(aminoalkyl) derivatives of 4-cyclopentylaniline and N-ethyl-4-cyclopentylaniline; Synthesis and pharmacological screening

Acylation of 4-cyclopentylaniline (I) with chloracetyl chloride, 3-chloropropionyl chloride, 4-chlorobutyryl chloride and 2-bromo-4-methylvaleryl bromide gave the halogenoacyl derivatives IV - VII out of which the first two were subjected to substitution reactions with diethylamine and piperidine. The N-(aminoacyl) derivatives VIII - XI obtained were reduced with lithium aluminium hydride to the N-(aminoalkyl) derivatives XII and XV. N-Ethyl-4-cyclopentylaniline (XVI), prepared by reduction of N-(4-cyclopentylphenyl)acetamide (II), was similarly transformed via the chloroacetyl derivative XVII to the amide XVIII and the diamine XIX. Salts of the compounds prepared (amino amides and diamines) bring about in higher doses central excitation which is apparently in close connection with the found discoordinating effect of a part of products (VIII - XI, XIII) in the rotarod test, further with the antireserpine effects in the tests of antagonization of reserpine ptosis and hypothermia (VIII, X, XII, XIII) and finally with the anorectic effect of compound X. All substances showed a mild spasmolytic effect of the anticholinergic type. On the other hand, the expected local anaesthetic effect was found only with compounds VIII, XVIII, XIX.

Tricyclic psychotropic agents containing two chalcogen atoms in the central ring: Synthesis of 6-(aminoalkyl) derivatives of 6H-dibenz[b,e]-1,4-oxathiepin

Heating of 2-(2-hydroxyphenylthio)benzoic acid (XX) with acetic anhydride gave dibenz[b,e]-1,4-oxathiepin-6-one (XXII). Demethylation of 2-(2-methoxyphenylthio)benzyl bromide (XI) with boron tribromide and the following treatment with aqueous sodium hydroxide in dimethyl sulfoxide afforded 6H-dibenz[b,e]-1,4-oxathiepin (I) which was halogenated with chlorine or N-bromosuccinimide only to the undesirable 2-halogeno derivatives II and III. A reaction of 2-(2-methoxyphenylthio)benzaldehyde (XII) with chloroform and 50% aqueous sodium hydroxide in the presence of triethylbenzylammonium chloride led to the α-chloro acid XIX whose demethylation with boron tribromide and the following cyclization with sodium hydroxide in dimethyl sulfoxide gave a mixture with prevailing 6H-dibenz[b,e]-1,4-oxathiepin-6-carboxylic acid (IV). Amino alcohols XXV-XXVIII were obtained by reactions of 2-(2-fluorophenylthio)benzaldehyde (XXIV) with the corresponding Grignard reagents and the products were cyclized with sodium hydride in dimethylformamide to the title compounds V-VIII. While compounds V and VI showed antireserpine effects and can be considered as potential antidepresants, compound VIII has a strong central depressant activity, brings about ataxia, hypothermia and potentiates the cataleptic action of neuroleptics (properties of a tranquillizer).

Mass spectrometry of π-complexes of transition metals : XX. Dimethylaminoalkyl derivatives of ferrocene and cymantrene; the determination of the distribution and the total content of deuterium label

The mass spectrometry behaviour of dimethylaminomethyl- and α-(dimethylamino)ethyl derivatives of cymantrene and ferrocene, their iodine methylates as well as of the deutero analogues of these compounds has been studied. It has been shown that mass spectrometry can be successfully employed for the quantitative determination of the total deuterium content in aminoalkyl derivatives of cymantrene and ferrocene, the distribution of the label between the dimethylaminoalkyl group and the metallocenyl fragment and in case of the dimethylaminomethylferrocene also between the substituted and unsubstituted cyclopentadienyl rings. The data on the distribution of the isotopic label were used to ascertain the mechanism of fragmentation of the dimethylaminomethylferrocene under electron impact.

Synthesis of new mono- and disubstituted hydroxyalkyl and aminoalkyl derivatives of heterocyclic bases

Synthesis of new mono- and disubstituted hydroxyalkyl and aminoalkyl derivatives of heterocyclic bases

Benzopyranopyridine derivatives. 1. Aminoalkyl derivatives of the azaxanthenes as bronchodilating agents.

The preparation of the four isomeric azaxanthones 3 and a number of their aromatic ring substituted derivatives is described. These ketones were converted into the title compounds which were examined for their biological properties. The most interesting compound in this series, the 1-methyl-4-piperidylidene derivative of 1-azaxanthene, shows the profile of an orally effective potent bronchodilating agent as well as a moderate antihistamine. Biological properties of this compound were compared to a number of antihistamines as well as known bronchodilating agents. Structure-activity relationships are also discussed.

ChemInform Abstract: CONDENSED HETEROTRICYCLES, POTENTIAL METABOLITES OF DIBENZ(B,F)(1,4)OXAZEPINE ANTIDEPRESSANT, SINTAMI

AbstractVerschiedene potentielle Metabolite des Antidepressivums Sintamil (Ia ° HCl) werden dargestellt.

Synthesis and pharmacological activity of aminoalkyl derivatives of substituted tryptamines

Synthesis and pharmacological activity of aminoalkyl derivatives of substituted tryptamines

Synthesis and study of the biological activity of aminoalkyl derivatives in the carbazole series

Synthesis and study of the biological activity of aminoalkyl derivatives in the carbazole series

Derivatives of 10,11-dihydro-5H-dibenzo(a,d)cycloheptene and related compounds. 6. Aminoalkyl derivatives of the aza isosteres.

Derivatives of 10,11-dihydro-5H-dibenzo(a,d)cycloheptene and related compounds. 6. Aminoalkyl derivatives of the aza isosteres.

Folate antagonists covalently linked to carbohydrates: Synthesis, properties, and use in the purification of dihydrofolate reductases

The folate antagonists, aminopterin and amethopterin, have been linked covalently via their carboxyl groups to various high molecular-weight water-soluble (starch, dextrans) and water-insoluble (cellulose, agarose) carbohydrates. The amount of folate compound incorporated into these polymers was determined by absorbance measurements and by radioactivity when 3H-labeled precursors were used. Optimal yields (ca. 150 mg/g) were obtained by using carbodiimides to effect amide linkages between the folate compounds and aminoalkyl derivatives of the carbohydrates. The soluble antagonist-carbohydrate complexes were characterized with respect to absorbance spectra, molecular weight, and ability to inhibit dihydrofolate reductase. Folate antagonists bound to carbohydrates retained an appreciable affinity for dihydrofolate reductases. This property has provided the basis for two different procedures for purification of these enzymes: (1) complex formation with amethopterin-aminoethyl- soluble starch and isolation of this complex via Sephadex G-100; and (2) affinity chromatography on amethopterin-aminoalkyl-Sepharose. Both methods were facilitated by the ability of dihydrofolate reductases to bind tightly to the antagonist at acidic pH values and the tendency for such complexes to dissociate at alkaline pH values, especially in the presence of dihydrofolate or folate.

Synthesis of aminoalkyl derivatives of 2-benzyl-5-hydroxyindole

Derivatives of 2-benzyl-5-methoxyindole-3-carboxylic acid are decarboxylated on heating and are converted to the corresponding 2-benzyl-5-methoxyindoles. 2-Benzyl-5-methoxygramine hydrochlorides were obtained from the latter and used to obtain (2-benzyl-5-methoxy-3-indolyl)acetonitriles. The nitriles were converted to 2-benzyl-5-methoxytryptamines by hydrogenation. A number of Mannich bases were obtained by aminomethylation of 2-benzyl-3-carbomethoxy-5-hydroxyindole derivatives.

α-ADRENERGIC BLOCKING ACTION OF NOREPHEDRINE-THEOPHYLLINE (NET) OBSERVED IN THE RENAL VASCULAR RESPONSE

Norephedrinetheophylline (NET), l-7[2-(1-methyl-2-hydroxy-2-phenyl-ethylamino)ethyl] theophylline hydrochloride, has molecules of caffeine and ephedrine in its chemical structure as follows: Since diuretic effects of aminoalkyl derivatives of theophylline were investigated by Hildebrandt (1) in 1952, pharmacological properties of these compounds have been elucidated by several workers (2, 3). Among these derivatives, NET was specially studied by Wagenmann and Taugner (4) and Mehmel et al. (5) on its cardiovascular effect. When caffeine and ephedrine are combined to NET, the pharmacological properties are very different from those of caffeine and ephedrine. NET does not show such a marked stimulatory effect on the central nervous system as that of constituents, and its positive chronotropic effect is very slight or converted to the negative one. These observations were attracting the authors' attention to test competition between this compound and catecholamines which seemed likely as a cause of diminution of the cardiovascular effect of this compound. The authors selected the renal vascular bed which is most sensitive to the adrenergic varoconstrictor action and very suitable to test α-adrenergic blocking effect of this compound.

Aminoacyl Derivatives of 2-Aminofluorene and 2,2′-Diamino-9,9′-Spirobifluorene

The synthesis of eight new aminoacyl derivatives of 2-aminofluorene and four new aminoacyl derivatives of 2,2′-diamino-9,9′-spirobifluorene are reported. The results of preliminary pharmacological testing of a few representative samples of these new compounds are also reported. A summary is given of negative results in the attempted preparation of analogous aminoalkyl derivatives.