Showing papers by "Novartis published in 1974"
TL;DR: Gel filtration of reduced and carboxymethylated relaxin preparations in 7 m guanidine hydrochloride showed that this hormone consists of two subunits (designated α and β) of nearly equal size linked by disulfide bond (s).
315 citations
TL;DR: From a strain of Aspergillus nidulans var.
Abstract: From a strain of Aspergillus nidulans var. echinulatus, A 32204, echinocandin, a novel polypeptide antibiotic complex with high and specific anti-yeast activity was isolated. The main component, echinocandin B, was separated by counter-current distribution. A tentative molecular formula C52H81N7O18 is discussed. The antibiotic is characterized by its IR. and NMR. spectra and by its characteristic hydrolytic degradation products: linoilic acid, L-4-hydroxyproline, L-4-oxoproline, (2S, 3S, 4S)-4-methyl-3-hydroxy-proline, L-threonine (2 mols), and 1-(p-hydroxyphenyl)-3-amino-propan-2-one.
218 citations
TL;DR: In this paper, a preliminary account is given of a total synthesis of human insulin involving directed formation of the three disulfide bonds at different stages of the fragment-condensation approach, facilitated by the application of two new methods for the selective removal of protecting groups.
Abstract: A preliminary account is given of a total synthesis of human insulin involving directed formation of the three disulfide bonds at different stages of the fragment-condensation approach. The synthesis was facilitated by the application of two new methods for the selective removal of protecting groups. In the first, two S-Trt-protected cysteine residues are converted to the disulfide without affecting S-Acm-protected cysteine residues. The second new method consists in a very mild, pH-controlled, acidolysis of N(α)-Trt, leaving intact N(α)-Bpoc and other acid-labile protecting groups. The last step of the synthesis was the formation of the disulfide bridge between the Acm-protected cysteine residues A7 and B7 by iodine. Extensive counter-current distribution yielded the synthetic hormone in pure form. It was compared and found to be identical with natural human insulin. Identification was achieved by means of thinlayer chromatography and electrophoretic procedures, as well as by comparing the pattern of break-down by enzymes (finger-printing). The natural and synthetic hormones were crystallized under identical conditions. The synthetic human insulin was found to possess full biological activity in an in vitro system.
104 citations
TL;DR: To arrive at a more precise morphological characterisation of the synaptic junction with respect to carbohydrate moieties, the capacity of the plant lectins concanavalin A and ricin, labelled with ferritin4, to bind to isolated synaptosomes and synaptic junctions is investigated.
Abstract: THE synaptic junction is the intercellular contact where bioelectrical impulses are transferred and transformed by neurotransmitters. The molecular mechanism of impulse transformation is still largely unknown. To understand this process, a detailed knowledge of the structure of the synaptic apparatus is essential. The available information on the morphology and cytochemistry of synapses has recently been reviewed1. To arrive at a more precise morphological characterisation of the synaptic junction with respect to carbohydrate moieties2,3, we investigated the capacity of the plant lectins concanavalin A (con A) and ricin, labelled with ferritin4, to bind to isolated synaptosomes (that is, pinched-ofT axon terminals) and synaptic junctions.
81 citations
Patent•
03 Jun 1974TL;DR: In this article, wherein R1 represents lower alkyl, cycloalkyl, or phenyl which is optionally substituted by halogen, lower alkyl, hydroxy, lower alkoxy, lower acid acid, or lower acidophilus.
Abstract: Compounds of the formula WHEREIN R1 represents lower alkyl, cycloalkyl or phenyl which is optionally substituted by halogen, lower alkyl or lower alkoxy, and one of the groups R2 and R3 represents phenyl which is optionally substituted by halogen, lower alkyl, hydroxy, lower alkoxy, lower alkylthio or lower alkylsulphonyl, and the other represents a 6-membered heteroaromatic radical containing 1 or 2 ring nitrogen atoms, their N-oxides and salts, with antiinflammatory, antinociceptive and antipyretic activity, they are active ingredients of pharmaceutical compositions and can be used for the relief and removal of pain as well as for the treatment of rheumatic, arthritic and other inflammatory complaints; an illustrative example is 2-isopropyl-4(5)-(p-methoxyphenyl)-5(4)3-pyridyl-imidazole.
60 citations
TL;DR: A continuous record of the conductivity was used as a simple and reliable method of determining specific growth stages and concomitant peaks in the activities of nitrate reductase and phenylalanine ammonia-lyase.
Abstract: Conductivity changes in the medium of cultured soybean (Glycine max L.) cells were shown to be strictly correlated with nitrate uptake and growth of the cultures. A continuous record of the conductivity was used as a simple and reliable method of determining specific growth stages and concomitant peaks in the activities of nitrate reductase and phenylalanine ammonia-lyase.
58 citations
TL;DR: Various antirheumatic drugs were tested in a newly described model of cartilage degradation-induced by the nonphagocytic release of neutral protease from viable human leukocytes in the presence of aggregated human IgG, suggesting that the activity of compounds in the model system described might predict their effect in vivo in rheumatoid arthritis.
Abstract: Various antirheumatic drugs were tested in a newly described model of cartilage degradation-induced by the nonphagocytic release of neutral protease from viable human leukocytes in the presence of aggregated human IgG. Steroidal and nonsteroidal antiinflammatory drugs inhibited the enzyme release process but not neutral protease activity, whereas gold and chloroquine inhibited the enzyme activity without affecting the release process. Several other drugs, known not to have antiinflammatory activity, were inactive. Neutral protease appears to be preformed in neutrophils and not induced by de novo synthesis during phagocytosis. The concentrations at which the antirheumatic drugs were active in vitro correlated with blood levels usually achieved in man. It is suggested that the activity of compounds in the model system described might predict their effect in vivo in rheumatoid arthritis.
55 citations
Patent•
18 Apr 1974TL;DR: In this article, a 6-membered heteroaromatic radical containing 1 or 2 ring nitrogen atoms is defined as an active ingredient of pharmaceutical compositions and can be used for the relief and removal of pain as well as for the treatment of rheumatic, arthritic and other inflammatory complaints.
Abstract: Compounds of the formula ##SPC1## Wherein R 1 represents lower alkyl, cycloalkyl or phenyl which is optionally substituted by halogen, lower alkyl or lower alkoxy, and one of the groups R 2 and R 3 represents phenyl which is optionally substituted by halogen, lower alkyl, hydroxy, lower alkoxy, lower alkylthio or lower alkylsulphonyl, and the other represents a 6-membered heteroaromatic radical containing 1 or 2 ring nitrogen atoms, their N-oxides and salts, with anti-inflammatory, antinociceptive and antipyretic activity, they are active ingredients of pharmaceutical compositions and can be used for the relief and removal of pain as well as for the treatment of rheumatic, arthritic and other inflammatory complaints; an illustrative example is 2-isopropyl-4(5)-(p-methoxyphenyl)-5(4)-3-pyridyl-imidazole.
53 citations
TL;DR: Baclofen exerts a pronounced muscle-relaxant effect in non-anaesthetized animals and affords protection against convulsions induced by thiosemicarbazide and pentetrazole but not against those due to electric shock strychnine or picrotoxin.
Abstract: Baclofen exerts a pronounced muscle-relaxant effect in non-anaesthetized animals. It reduces experimental rigidity in surgically and in anaemically decerebrated cats. It decreases monosynaptic and polysynaptic reflex transmission, as well as post-tetanic potentiation of the monosynaptic mass reflex in about the same dosage range. It reduces the activity of γ-moioneurones. It has no effect on neuromuscular transmission or on the sensory input from de-efferented muscle spindles and from slowly adapting pulmonary stretch receptors.The compound affords protection against convulsions induced by thiosemicarbazide and pentetrazole but not against those due to electric shock strychnine or picrotoxin.
47 citations
45 citations
TL;DR: Thyrotropin-Releasing Hormon erzeugt unmittelbar nach i.v. Injektion an Pentobarbital-narkotisierten Ratten einen feinschlägigen Tremor und Haarsträuben werden durch eine direkte zentralnervöse Wirkung von TRH ausgelöst.
Abstract: Thyrotropin-Releasing Hormon (TRH) erzeugt unmittelbar nach i.v. Injektion an Pentobarbital-narkotisierten Ratten einen feinschlagigen Tremor und Haarstrauben. Diese Symptome werden durch eine direkte zentralnervose Wirkung von TRH und nicht durch Stimulation der Schilddruse ausgelost. Die Wirkung ist dosisabhangig und spezifisch fur das Tripeptid pGlu-His-Pro.
TL;DR: A sensitive analytical procedure was developed for the measurement of the concentrations of hydralazine in human plasma and urine based on the formation of the hydrazone derivative of Hydralazine with p-methoxybenzaldehyde.
TL;DR: It was shown that Fe(3+) is reduced before uptake of chelated iron by the root, and reduction also takes place when Fe is used in ionic form, and the removal of Fe from the chelate complex after reduction to Fe(2+) seems to present no difficulties to the various plant species.
Abstract: The Fe requirements of four monocotyledonous plant species (Avena sativa L., Triticum aestivum L., Oryza sativa L., Zea mays L.) and of three dicotyledonous species (Lycopersicum esculentum Mill., Cucumis sativus L., Glycine maxima (L.) Merr.) in hydroponic cultures were ascertained. Fe was given as NaFe-EDDHA chelate (Fe ethylenediamine di (O-hydroxyphenylacetate). I found that the monocotyledonous species required a substantially higher Fe concentration in the nutrient solution in order to attain optimum growth than did the dicotyledonous species. Analyses showed that the process of iron uptake was less efficient with the monocotyledonous species. When the results obtained by using chelated Fe were compared with those using ionic Fe, it was shown that the inefficient species were equally inefficient in utilizing Fe3+ ions. However, the differences between the efficient and the inefficient species disappeared when Fe2+ was used. This confirms the work of others who postulated that Fe3+ is reduced before uptake of chelated iron by the root. In addition, it was shown that reduction also takes place when Fe is used in ionic form. The efficiency of Fe uptake seems to depend on the efficiency of the root system of the particular plant species in reducing Fe3+. The removal of Fe from the chelate complex after reduction to Fe2+ seems to present no difficulties to the various plant species.
TL;DR: A method is described for the simultaneous automated fluorometric estimation of noradrenaline and dopamine in brain extracts based on a slight modification of the automated method for dopamine published recently.
Abstract: A method is described for the simultaneous automated fluorometric estimation of noradrenaline and dopamine in brain extracts. It is based on a slight modification of the automated method for dopamine published recently. Interference of noradrenaline in the estimation of dopamine, and vice versa, is low (0.8 and 1.4%, respectively). Interferences of other catechols and related compounds have also been studied. Samples can be processed at a rate of 30 per hour, and the limit of sensitivity for both amines is about 2 ng/ml of brain extract.
TL;DR: In this paper, the 3-methylidene-esters were obtained by ozonolysis of the corresponding 3-hydroxy-ceph-3-em-esters 3 a-c. Reduction and elimination gave the 3unsubstituted ester 13; derivatives 16 a−c and 20−22 resulted from O-alkylation.
Abstract: 3-Hydroxy-ceph-3-em-esters 5 a–c, versatile intermediates for the preparation of new β-lactam antibiotics, were obtained by ozonolysis of the corresponding 3-methylidene-esters 3 a–c. Reduction and elimination gave the 3-unsubstituted ester 13; derivatives 16 a–c and 20–22 resulted from O-alkylation. The 3-methoxy-esters 16 a–c were converted into the corresponding acids 23 a–d. Several other transformations of the β-ketoester system are described.
TL;DR: In contrast to butyllithium, ethylmagnesium-bromide reacts with 1-phenyl-pyrazole exclusively by deprotonation, at the ortho position of the phenyl-ring.
Abstract: In contrast to butyllithium, ethylmagnesium-bromide reacts with 1-phenyl-pyrazole exclusively by deprotonation, at the ortho position of the phenyl-ring. With nitriles the intermediate 2-(1-pyrazolyl)-phenylmagnesiumbromide gave good to excellent yields of 1-(2-aroyl or 2-hetaroyl-phenyl)-pyrazoles (Table 1, compounds 5a–5i); with ketones the corresponding methanol derivatives (Table 2, compounds 6a–6c) were found, whilst CO2 yielded the corresponding 1-(2-carboxyphenyl)-pyrazole (3). Surprisingly enough, 1-(o-bromo-phenyl)-pyrazole and magnesium did not yield a single product, but a mixture of 3 compounds, which on reaction with 4-benzoylpyridine gave the three alcohols 19, 20 and 21.
Patent•
27 Sep 1974TL;DR: The bis-stilbene compounds as discussed by the authors correspond to the formula R.sub.2 in which X represents a diphenyl residue bound in positions 4 and 4' to the =CH-- groups; R 1 and R 2 independently of each other, each represents a monocyclic benzene residue, a diphensyl, naphthyl or pyridyl residue.
Abstract: The present invention provides the new bis-stilbene compounds, which are useful as optical brighteners and correspond to the formula R.sub.1 -- CH = CH -- X -- CH = CH -- R.sub.2 in which X represents a diphenyl residue bound in positions 4 and 4' to the =CH-- groups; R 1 and R 2 independently of each other, each represents a monocyclic benzene residue, a diphenyl, naphthyl or pyridyl residue, and in which at least one of the cyclic systems R 1 , R 2 , X contains a possibly functionally modified sulphonic acid group, a sulphone group, a possibly functionally modified carboxylic acid group, a nitrile, hydroxyl, mercapto or methyl group.
Patent•
18 Apr 1974TL;DR: The dry soil repellent properties of a fluorochemical textile resin useful to impart oil and water repellency to textiles can be improved by the presence of a quaternary ammonium salt containing a long hydrocarbon chain this article.
Abstract: The dry soil repellent properties of a fluorochemical textile resin useful to impart oil and water repellency to textiles can be improved by the presence of a quaternary ammonium salt containing a long hydrocarbon chain. The oil and water repellent properties are not adversely affected.
TL;DR: The metabolism of atrazine and 6 possible metabolites by rat liver subcellular fractions was studied in vitro; the dealkylation reaction predominated over the conjugation reaction with glutathione; the isopropyl group being more easily dealkYLated than the ethyl group.
TL;DR: The boundaries between the white space and color space are discussed, to discuss the application of the tristimulus weighting functions to low-purity colors, and to show the correlation between visual appraisals of white with those derived from physical measurements.
Abstract: The CIE tristimulus weighting functions have been applied to the colorimetric description of white surfaces. These functions, however, were derived from visual comparisons of high-purity colors, whereas white surfaces represent low-purity colors. No paper has dealt with the question of tristimulus weighting functions for low-purity white surfaces. The object of this paper is to discuss the boundaries between the white space and color space, to discuss the application of the tristimulus weighting functions to low-purity colors, and to show the correlation between visual appraisals of white with those derived from physical measurements.
TL;DR: The earliest structure in the development of the glomerulus, unequivocally recognizable as such by scanning electron microscopy, is the nephrogenic vesicle which develops through the inductive action of the terminal ampullae of the growing collecting ducts.
Abstract: Publisher Summary This chapter discusses the scanning electron microscopy analysis of structure and development of the renal glomerulus. The main advantage of scanning electron microscopy is the ease with which information on the spatial arrangement of surface structures can be obtained over a wide range of magnification. The renal corpuscle of the vertebrate kidney can be thought of as the puffed proximal end of the renal tubule, the vertex of which is depressed to form a double-walled cup. This cup contains a tuft of capillaries. The inner wall, or visceral layer, adheres closely to the capillaries; it forms the outermost coat around them, and becomes part of the capillary wall. The outer wall, or parietal layer, is separated from the visceral layer by the so-called Bowman's space. This space, which almost completely surrounds the capillary tuft, receives an ultrafiltrate formed by sieving of plasma through the glomerular capillary wall. At the urinary pole of the corpuscle, the ultrafiltrate drains into the renal tubule, where it is transformed into the final urine. The earliest structure in the development of the glomerulus, unequivocally recognizable as such by scanning electron microscopy, is the nephrogenic vesicle. This vesicle develops through the inductive action of the terminal ampullae of the growing collecting ducts.
Patent•
04 Feb 1974TL;DR: In this article, the free-radical catalyzed addition of a perfluoroalkylthio glycol to an acetylenic alcohol or ester thereof is described. And the compounds obtained are useful intermediates for the synthesis of fluorochemicals with low free surface energies having oil and water repellent properties.
Abstract: Perfluoroalkylthio glycols and esters thereof can be prepared by the free-radical catalyzed addition of a perfluoroalkylthiol to an acetylenic alcohol or ester thereof. The compounds obtained are useful intermediates for the synthesis of fluorochemicals with low free surface energies having oil and water repellent properties. In one embodiment, a perfluoroalkylthio glycol can be reacted with a diisocyanate to obtain a polyurethane containing perfluoroalkylthio groups, which polyurethanes are useful as coatings to provide oil and water repellence to textiles and as additives to plastics to provide mold-release and other desirable properties.
Patent•
29 Jul 1974TL;DR: In this article, a process for deodorising waste or exhaust gases, preferably containing CO2, in at least two washing stages with introduction of active chlorine, wherein a stream of the waste gas to be deodorised is subjected in an initial chlorine washing stage to the action of a washing liquid containing active chlorine and in a subsequent chlorine washing operation to an alkaline pH is described.
Abstract: A process for deodorising waste or exhaust gases, preferably containing CO2, in at least two washing stages with introduction of active chlorine, wherein a stream of the waste gas to be deodorised is subjected in an initial chlorine washing stage to the action of a washing liquid containing active chlorine and in a subsequent chlorine washing operation to the action of a washing liquid, likewise containing active chlorine, of alkaline pH is described. This process is improved by the following features: A. THE SUPPLIED ACTIVE CHLORINE IS PRACTICALLY FREE FROM CHLORINE DIOXIDE; B. A CONTENT OF AT LEAST 0.02 G OF ACTIVE CHLORINE PER LITRE OF WASHING LIQUID IS MAINTAINED IN AT LEAST ONE OF THE WASHING STAGES; C. THE PH-value of the washing liquid in the first washing stage, through which the waste gas to be purified, is flowing, is kept to between 4 and 9, and D. THE PH-value of the washing liquid in the subsequent washing stage is kept between 7 and 11, with the pH-value in the said subsequent washing stage being adjusted to remain higher by 0.3 to 4 than the pH-value in the first stage; E. ACTIVE ALKALI IS ADDED IN AN APPROXIMATELY STOICHIOMETRIC AMOUNT, CALCULATED ON TOTAL ACTIVE CHLORINE SUPPLIED, IN A SUBSEQUENT WASHING STAGE.
TL;DR: In this paper, the reaction of imidazoles with DCCI leading to such compounds and their cleavage have been investigated, and the significance of this side-reaction in peptide synthesis is discussed.
Abstract: In the synthesis of histidine peptides by means of the carbodiimide method the formation of Nim-amidino-histidine derivatives as secondary products has been observed. The reaction of imidazoles with DCCI leading to such compounds and their cleavage have been investigated. The significance of this side-reaction in peptide synthesis is discussed.
Patent•
21 Nov 1974TL;DR: Esters of 2,2,6,6-tetramethylpiperidinols with mono- or bis-hydroxybenzylmalonic acids are powerful stabilizers for organic polymers, especially for polyolefins as mentioned in this paper.
Abstract: Esters of 2,2,6,6-tetramethylpiperidinols with mono- or bis-hydroxybenzylmalonic acids are powerful stabilizers for organic polymers, especially for polyolefins They protect the polymers against thermal-oxidative degradation as well as against light-induced aging Similar activity show the corresponding amides of hydroxybenzylmalonic acids The esters and the amides can be prepared by analogous processes
Patent•
05 Dec 1974TL;DR: In this article, a process for bonding and providing nonwovens with an antimicrobial finish is provided, which comprises treating the non-worns with aqueous preparations of 1.sub.y. aminoplast precondensates which contain alkyl ether groups.
Abstract: A process for bonding and providing nonwovens with an antimicrobial finish is provided, which comprises treating the nonwovens with aqueous preparations of 1. reaction products of (a) an epoxide that contains at least two epoxide groups in each molecule, (b) a fatty amine with 12 to 24 carbon atoms, (c) a dicarboxylic acid of the formula HOOC(CH.sub.2).sub.y.sub.-1 COOH, wherein y is an integer from 1 to 13, optionally (d) an anhydride of an aromatic dicarboxylic acid with at least 8 carbon atoms, of an aliphatic monocarboxylic acid with at least 2 carbon atoms, or of an aliphatic dicarboxylic acid with at least 4 carbon atoms, (e) an aliphatic diol with 2 to 21 carbon atoms and/or (f) a difunctional compound which differs from components (a), (c), (d) and (e), which reaction products have been reacted or mixed or reacted and mixed with 2. aminoplast precondensates which contain alkyl ether groups, and subsequently drying the treated nonwovens at elevated temperature. The finished nonwovens show a good strength, a softhandle a good fastness to washing, solvents and shampooing and simultaneously good antimicrobial effects.
TL;DR: Rat peritoneal cell suspensions were labeled in vitro with 51 Cr and then adoptively transferred intravenously into isologous recipients and an analysis of the circulating radioactivity indicated that ≅ 80 per cent was cell-associated.
Patent•
22 Jul 1974TL;DR: In this article, a process for uniformly coating granular fertilizer formulations with one or more chelated metallic micronutrients is described, which comprises the following steps: blending a granular formulation in, for instance, a rotary drum mixer; spraying, while the blending continues 1 to 5% by weight of an aqueous solution or slurry containing one of the chelated items, such as Na 2 Zn EDTA, onto said fertilizer formulation; and adding, before or after said spraying, and while blending continues, a finely divided water-absorbent additive, such
Abstract: A process for uniformly coating granular fertilizer formulations with one or more chelated metallic micronutrients which comprises the following steps: blending a granular fertilizer formulation in, for instance, a rotary drum mixer; spraying, while the blending continues 1 to 5% by weight of an aqueous solution or slurry containing one or more chelated metallic micronutrients, as for example, Na 2 Zn EDTA, onto said fertilizer formulation; and adding, before or after said spraying, and while the blending continues 1 to 4% by weight of a finely divided water-absorbent additive, such as, a synthetic calcium silicate or finely divided silica, to the fertilizer formulation. The finished fertilizer formulation then contains 0.05 to 0.5% by weight of micronutrient.