Pyranylidene-anthrones (author's transl)]

Pyranylidene-anthrones . The 2,6-diphenyl-pyrones 1a , 1b and the distyrylpyrones 13a – e react with anthrone in acetic anhydride to the pyranylidene-anthrones 3a , 3b and 14a – e . Condensation, hydrogenation, oxidation and substitution reactions of these compounds are described.     

Dihydroisoquinoline-rearrangement (author's transl)]

Dihydroisoquinoline-Rearrangement . The synthesis of 1-picolyl-1,2-dihydroisoquinoline 7 is reported. With acids 7 gives not the expected rearrangement, but elimination of the C- 1 -substituent leading to the products 8 and 9 . Surprisingly this elimination-reaction occurs also in the polar solvents methanol or water at room temperature in quantitative yield.     

Polychlorodibenzo-p-dioxins (author's transl)]

Polychlorodibenzo-p-dioxins (chlorodioxins) appear most frequently by heating of chlorophenols in alkaline solution specially when producing organic derivatives. Consequently chlorodioxins may contaminate several industrial chemical products largely used, for instance, as pesticides. Occasionally, chlorodioxins are also synthesized from chlorophenols or their derivatives in situ during industrial processes. Chlorodioxins are the cause of chloracne and chick edema which killed thousands of broiler chickens in the U.S.A. Furthermore chlorodioxins seem to be foetotoxic possible even for man. The present paper is the first part of our work. It is a review of the chemical and toxicological properties of chlorodioxins. We hope to publish later a review of analytical methods and the results of our analyses.     

Hypothalamo-pituitary-adrenocortical (HPA) function in the morphine dependent rat (author's transl)]

Morphine dependence was induced by ten daily administrations of morphine with gradually increasing dosage (40--160 mg/kg/day s.c.) to male Sprague-Dawley rats, the dosage being divided in 2/day for the first 8 days and 4/day for the last 2 days. Diurnal variation in body weight in morphine dependent rats was the same as in naive rats. Although body temperature in the naive rats showed a diurnal variation with the highest at 3:00 and the lowest at 15:00, in the morphine dependent rats there was no distinct variation. Plasma corticosterone level (PC) in naive rats showed diurnal variation with the peak at 21:00 and the trough at 9:00. PC in morphine dependent rats showed the same diurnal variation as did the naive rats, while such disappeared following pentobarbital anesthesia (80 mg/kg i.p. for 45 min) and PC was low all during the day. The PC increase following formalin administration to morphine dependent rats was higher than in naive rats. 0.1 mg/kg s.c. of dexamethasone completely inhibited PC increase after formalin in naive rats, but the dexamethasone inhibition in morphine dependent rats was not complete even with a larger dose, i.e. 10 mg/kg s.c. Diurnal variations and other differences were not detected in the adrenal response to ACTH (in vivo, in vitro) between naive and morphine dpendent rats. These results suggest that HPA function takes part in the development of morphine dependence.     

Pyridyl- and piperidyl-histamines (author's transl)]

Pyridyl- and Piperidyl-histamines The three 2-substituted histamine isomers of piperidyl- (7) as well as pyridyl-histamines (6) were synthesized from the corresponding 2-substituted 4-hydroxymethyl-imidazoles (8) or 4-(2-hydroxyethyl)-imidazoles (3) by two different ways and tested for their histamine-like activity.     

Aminobenzyl- and aminocyclohexylmethyl-imidazoles (author's transl)]

Aminobenzyl- and Aminocyclohexylmethyl-imidazoles . From the isomeric bromomethyl-nitrobenzyl ketones 7a – c , produced by Arndt-Eistert synthesis, the 4-nitrobenzyl imidazoles 8a – c were synthesized by cyclisation with formamidineacetate ( 6 ) in liquid ammonia or by Bredereck synthesis. These were transformed by gradual hydrogenation into the 4-aminobenzyl imidazoles 9a – c and the 4-aminocyclohexylmethyl imidazoles 10a - c . 9 and 10 were examined for histamine-like activity.     

Methaqualon-like benzothienopyrimidines (author's transl)]

Methaqualon-like Benzothienopyrimidines A group of basically substituted 2-methyl-3-(o-tolyl)-5,6,7,8-tetrahydro[1]benzothieno[2,3- d]-pyrimidin-4(3H)-ones Ia–d was synthesized by cyclization of the corresponding 2-acylamino-5,6,7,8-tetrahydrobenzo[b]thiophene-3-carboxylic o-toluidides. The methaqualone analogues 4a and 4b were also prepared, preferably via the ethoxymethylene compunds 3a and 3b .     

Androsace septentrionalis (author's transl)]

Morphology, culture requirements, and medicinal effects of Androsace septentrionalis L. (Primulaceae) are described. In mice, water extracts of the plant (.5 ml/100g body weight) produced disturbances of the menstrual cycle and infertility after copulation. Histological studies showed enlargement of glandular mucosa cells and increased uterine connective tissue. Compared with controls, more corpora lutea were found in the fallopian tubes of treated animals. The plant is used in Siberian folk medicine for angina, heart diseases, epilepsy, gonorrhea, and as a contraceptive. The contraceptive and tranquilizing effects of the water extract of Androsace were evident in this experimentation.     

Tetrahydrobenzodipyrandiones and tetrahydrobenzodipyrans (author's transl)]

Tetrahydrobenzodipyrandiones and Tetrahydrobenzodipyrans From the bis-(2-carboxyethoxy)-benzenes 2a , b and c the tetrahydrobenzodipyrandiones 8a – 12a are obtained with acids. Catalytic hydrogenation of 8a – 12a leads to the tetrahydrobenzodipyrans 13 – 17 . From 12a the bis-benzylidene and aminomethylene-derivatives 19a – c were prepared.     

Pharmacokinetic studies of the propolis constituent pinocembrin in the rat (author's transl)]

The present investigation into the pharmacokinetic behaviour of the propolis constituent pinocembrin which produces a relatively good antimicrobial effect in vitro, points to possible causes of its therapeutical failure when mice infected with Candida albicans were used as a model. The biological half-life periods for the phases of invasion and elimination were 26 and 268 min, respectively. The biological availability was 25%. Almost 15% of pinocembrin are excreted unchanged in faeces and urine. Even in case of oral application of doses of up to 500 mg/kg, the serum pinocembrin concentrations did not equal the MIC (minimal inhibitor concentration) values required in vitro. A considerable first-pass effect and accelerated processes of elimination are discussed as possible causes. It appears from the present findings that pinocembrin may be utilizable only for the external treatment of stomatomycoses.     

Investigation of the ninhydrin-reaction (author's transl)]

Investigation of the Ninhydrin-Reaction Reaction of ninhydrin (1) with 4-methoxyaniline yields the stable ketimine 5 . 2-Methoxyaniline reacts to different products. The analogous ketimine 10a is unstable but it is possible to isolate stable subsequent products.     

Volatile terpenes in fungi (author's transl)]

Volatile Terpenes in Fungi . The following volatile metabolites of a newly isolated mutant from Ceratocystis coerulescens strain 765, have been identified for the first time in this fungus: citronellol, α-terpineol, nerol, geraniol, the acetates of these monoterpene alcohols, linalool, nerolidol, di- and tetrahydronerolidol, farnesol, 2,3-dihydro-6-trans-farnesol and its acetate. The sesquiterpene components have never before been isolated from fungi. Changes in the composition of all volatile metabolites during fungal growth were analyzed.     

Substituted isatin phenylimines (author's transl)]

Substituted Isatin Phenylimines . 5-Bromo- and 5-nitro-isatin condense with substituted anilines to isatin-3-(phenyl)-imines. 5-Bromo-isatin-3-(phenyl- and naphthyl)-imine are obtained also by bromination of isatin-3-(phenyl- and naphthyl)-imine. The reaction with o-phenylenediamine gives ring closed 5-bromo-and 5-nitro-6,11-diaza-5H-benzo-[b]-carbazoles. The isatin-3-(o-aminophenyl)-imines may act as intermediates in this reaction.     

3beta-substituted tropane-derivatives (author's transl)]

3β-Substituted Tropane-Derivatives An approach to synthesize nortropane-3β-acetic acid ( 1a ) and related compounds is described. The 3α-isomer 2a is readily obtainable. Nortropane-3β-derivatives e.g. 5h are synthesized via N-benzyl-nortropanes. The salt 7 prevents the conversion to tropane-3β-compounds with two carbon atoms in the chain. The configuration of the described tropanes is established by NMR-spectroscopy.     

Ototoxicity of spectinomycin (author's transl)]

Spectinomycin is an aminocyclitol antibiotic, but different in chemical structure from other aminocyclitol antibiotics such as streptomycin, kanamycin and gentamicin. Spectinomycin clinically has been proven to be highly effective in the intramuscular single-dose treatment of gonorrhea. According to NOVAK et al. (1974), all evidence from pharmacological and clinical efficacy studies to date indicates that spectinomycin is free from ototoxic effects at the dose levels recommended for single-dose treatment of gonorrhea (2 or 4 g) or repeated i.m. or i.v. doses, 8g/day. The present experimental study has been made to evaluate the ontoxocic effects of spectinomycin in Hartley strain guinea pigs given i.m. a single-high dose (800 mg/kg or 1,600 mg/kg) and repeated-slightly higher dose (80 mg/kg or 160 mg/kg daily for 4 weeks) respectively. Differential frequency pinna reflex test in frequency range from 20 KHz to 500 Hz revealed that no animals showed disappearance of pinna reflex in the frequencies tested. Histologic examination in serial celloidin sections of the cochlea and vestibulum disclosed that a few animals given a single-high dose of spectinomycin (800 mg/kg or 1,600 mg/kg) and repeated-slightly higher dose or spectinomycin (80 mg/kg daily for 4 weeks) respectively showed limited mild damage of outer hair cells in the spiral organ and of hair cells in the vestibular organ. There were histologically a few focal necrosis in the liver and scattered interstitial cell infiltration around the proximal convoluted tubules which are lined with regenerated epithelial cells in some animals given the single-high dose (800 mg/kg or 1,600 mg/kg) or repeated-slightly higher dose (80 mg/kg or 160 mg/kg daily for 4 weeks) of spectinomycin. Positive correlation between the extent of the hair cell damage and the injury of the liver and kidney was not confirmed. The present study suggests that administration of spectinomycin at the dose levels recommended for single-dose treatment of gonorrhea (2 or 4 g) most probably is free from ototoxic effect.     

Metabolism and elimination in the rat of the thalidomide-like compound K-2004 (author's transl)]

Metabolism and Elimination in the Rat of the Thalidomide-like Compound K-2004 After oral application of the ³H-labelled test compound K-2004, a non-teratogenic congener of thalidomide, 10 structurally defined metabolites have been detected in rat urine; 9 of these resulted from simple hydrolytical cleavage of the parent compound and one by conjugation with glucuronic acid. Only 10% of the applied dose are excreted unchanged. The biological half-lives of the unchanged test compound (2,84 h) and of its main metabolite (3,59 h) have been calculated from urine excretion data.     

Photoreactions of phthalimide (author's transl)]

Photoreactions of Phthalimide Irradiation of phthalimide in a mixture of dioxane and acetone leads to the photo compounds 1, 2, 3 and 4 ; in isopropanol 2, 3 and 4 , in ethanol 2, 3 and 5 , in methanol 2 and 3 are produced.     

Ditertiary diamine compounds (author's transl)]

The preparation of ditertiary aliphatic diamines 3 designed as drugs protecting CNS acetylcholinesterase against organophosphate inhibition, is described. Owing to the radicals at the basic nitrogen atoms, these compounds should exist in appreciable amounts both as base and as diammonium ion at biological pH's.