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The methylation of parazoanthoxanthin D ( 1 ) and zoantboxanthin ( 2 ), two natural tetrazacyclopentazulene pigments from Parazoanthus axinellae , has been examined under various conditions. As a rule, methylation in neutral or acidic conditions proceeds preferentially at N-1, while in liquid ammonia zoanthoxanthins are attacked by methyl iodide exclusively at the amino group at C-2. In addition to providing information on zoanthoxanthin tautomerism, the availability of various synthetic derivatives ( 3–10 ) led to the identification of the methyl derivatives 4 and 9 in Parazoanthus axinellae , and of 5 in Epizoanthus arenaceus , another zoanthid commonly found in the Bay of Naples.

The synthesis of the protected octapeptide N-t-butoxycarbonyl-phenylalanyl-valylasparaginyl-glutaminyl-Nim-tritylhistidyl-leucyl-S-benzhydrylcysteinyl-glycine-hydrazide 1 , corresponding to the amino-terminal sequence of the insulin B-chain, is described. Up to the protected octapeptide all intermediates have greatly improved solubility properties in neutral organic solvents in comparison with other synthetic derivatives of the same sequence.

Summary New synthetic derivatives of natural cyclic nucleotides have been tested for their metabolic (blood glucose and plasma corticosterone) and cardiovascular (heart rate and blood pressure) effects in the rat. A clear cut specificity of the effects emerges from the comparison between the different series of substituted nucleotides (N 6 , 2′O-8-and 2-substitutions). A long lasting effect on plasma steroid levels has been demonstrated with the compound 6-(3′4′-dimethoxyphenyl-)ethyl-amino-3′,5′-PuMP + , at doses and times where there is no effect on the cardiovascular parameters or blood glucose levels.

THE estrogens are the most widely used and abused of endocrinal substances. When they are used physiologically and intelligently they are valuable preparations. However, there are those who feel that their widespread misuse may more than outweigh their value. In these random comments we shall discuss a few observations on the use of estrogens. The ingenuity of our chemists and pharmaceutical companies has provided us with a host of preparations. In the first place there are the natural estrogens and their derivatives. The basic substances estradiol, estriol and estrone have been extracted from a variety of sources. Estradiol is the most potent naturally-occurring estrogen; estriol and estrone are much less potent, for these are the products of metabolism of estradiol. The naturallyoccurring estrogens are available in pure form, in impure mixtures such as the conjugated estrogens, and as synthetic derivatives such as ethinyl estradiol. Lastly, there are the stilbene-hexane compounds, chemically unrelated t...

During the past decade there has been a considerable difference of opinion as to the comparative efficiency of ephedrine and its synthetic derivatives in the treatment of nasal obstruction. Previous attempts to determine their specific action in the obstructed nose have not provided reliable data, largely because of the limitations of the methods employed. In 1936 Schur and I 1 first described a new method for the quantitative measurement of nasal patency. The patency of the nasal airway was easily and accurately determined in terms of resistance to nasal air flow. 2 This method was employed to evaluate the rate and degree of nasal shrinkage. The present study deals with the quantitative effects of ephedrine, cocaine and some proprietary synthetic preparations administered in different concentrations and forms on the erectile tissue in the pathologic nose. APPARATUS AND PROCEDURE The apparatus (fig. 1) consists of a nasal catheter ( F ), a flowmeter

Besides the well-known side effects, long term corticosteroid treatment in pharmacological doses causes inhibition of statural growth in children. This is of special importance in asthmatic children, since their growth may be impaired by the disease itself. The degree of inhibition of growth depends on the type of corticosteroids used (the inhibition by synthetic derivatives is stronger than that by hydrocortisone), on the dosage, and on the duration of treatment. The mechanisms leading to an inhibition of growth are not fully understood: possibly the corticosteroids inhibit the release of growth hormone from the pituitary, or they antagonize the metabolic action of growth hormone peripherally. In an effort to avoid the growth-inhibiting effect of corticosteroids, different approaches have been tried: Replacement of corticosteroids by ACTH seems to have normalized the growth rate in some cases, but failed to do so in others. A final evaluation of the value of ACTH with respect to growth can therefore not yet be made. At the present time, therapy with corticosteroids at an alternate day schedule seems to be promising: the daily dosage is doubled, but the corticosteroids are given only every other day. Treated in this way, the patients observed so far, have been able to maintain a normal growth rate.

THERE is considerable interest in the effects of prostaglandins on blood platelets, partly because the synthesis of prostaglandins by stimulated platelets is important in haemostasis, and partly because platelets can be used as models to investigate the actions of prostaglandins (PGs) at a cellular level1. The effects of different PGs on platelets are diverse: PGE1 is a potent inhibitor of platelet aggregation2 with a Ki value around 30 nM and PGD2 is an even more effective inhibitor of aggregation of human platelets, but not those of some other species3,4. PGE2 inhibits platelet aggregation at high concentrations (> 1 × 10−6 M), and there is some controversy as to whether lower concentrations enhance aggregation5. When human platelets are stimulated by collagen they synthesise PGE2 from arachidonic acid6 and the cyclic endoperoxide intermediates in the biosynthesis of PGE2 exert a direct aggregating effect7,8. Synthetic derivatives of PGE2 can also induce the aggregation of human platelets9, but PGE2 itself has never been found to induce aggregation directly.

Publisher Summary This chapter discusses antibiotics that can be used pharmaceutically in agriculture or in basic research, including chemically related antibiotics, semisynthetic and synthetic derivatives, and analogues. Antibiotics are microbial metabolites possessing antimicrobial, cytotoxic, antitumour, antinematodal, or insecticidal properties. Antibiotics belong to very different groups of organic compounds, but until now, a classification from a chemical point of view has been virtually nonexistent. The samples of various qualities can be applied on to chromatographic columns. They include the filtrates and extracts of fermentation broths, the crude concentrates of antibiotics, partially purified substances, and pharmaceutical preparations. The classical and modern techniques of column chromatography are indispensable tools in the study and preparation of antibiotics. They are used mainly for the following purposes: (1) laboratory and commercial isolation and the purification of antibiotics, (2) the separation of the mixtures of antibiotics, (3) structural studies, (4) studies of the biogenesis and the preparation of labeled antibiotics, (5) studies of the chemical modifications and biotransformations of antibiotics, and (6) purity control.

Publisher Summary Interest in studying the effects of structural modification of the naturally occurring steroid hormones upon activity has been evident ever since the elucidation of the structure of the sex hormones in the early 1930s. Emphasis on this particular field of steroid research was the result, first, of a natural curiosity to determine the chemical features essential for the complex hormonal activities of androgens, estrogens, and progestagens, and, secondly, of the very practical consideration of obtaining more desirable agents at lower cost for use in both human and veterinary medicine. Some of the features considered desirable for this purpose were, and still are, peroral effectiveness, high potency, extended duration of action, the separation of anabolic from androgenic and of gonadotropininhibiting from estrogenic activity. It soon became evident that, with the exception of the estrogens, the steroidal sex hormones are highly specific in their dependence of activity upon structure, and that only a limited number of structural variations would result in the retention of any biological activity, not to speak of increases in potency or separation of the physiological components involved.

Die Pflanze beherrscht die Synthese der zur Therapie der Herzinsuffizienz verwendeten Glykoside auch heute noch besser als die Chemiker. Das ist nicht verwunderlich, wenn man bedenkt, das schon die Auflosung einer Doppelbindung oder eine sterische Umlagerung die kardiotone Wirkung weitgehend zum Verschwinden bringen kann. Trotzdem hat es nicht an Versuchen gefehlt, der Natur ins Handwerk zu pfuschen. Ich mochte das mir gestellte Thema von der arztlichen Seite angehen und die Frage stellen, welcher Fortschritt in der Therapie durch die halbsynthetische Abwandlung kardiotoner Glykoside angestrebt werden kann und was bisher auf diesem Wege erreicht wurde.

Publisher Summary This chapter attempts to report progress in antitussive therapy achieved over the past twenty years. The chapter discusses the drugs that have a direct and specific action on the cough reflex, including the opium alkaloids, their synthetic derivatives and substitutes, and newer non-narcotic compounds. Such a classification eliminates adjuvant drugs such as expectorants and antibiotics that are generally used in the treatment of cough-accompanying respiratory disorders. The chapter states that antitussives with a selective anaesthetic activity on the stretch receptors of the lung have been developed. Morphine, codeine, and their derivatives act on central respiratory mechanisms, and codeine is generally accepted as the prototype of antitussives having a central point of attack. The chapter also reviews that the final stage in the development of a new antitussive drug is the clinical evaluation, and discusses whether to use patients suffering from pathological cough or individuals with an experimentally induced cough.

A number of synthetic derivatives of the essential amino acid leucine were tested for biological activity using the growth of rats as the main criterion. Of these, glycyl- l -leucine, acetyl- l -leucine, l -leucine ethyl ester, and l -leucine methyl ester supported growth while caproic acid, phthaloyl- l -leucine, benzoyl- dl -leucine, and carbobenzoxy- l -leucine were found to be inactive. Chloroacetyl- l -leucine actually suppressed growth to a greater degree than a leucine-deficient diet. The N-methyl derivative of leucine was only slightly active. Comparison of the N-acetyl derivatives of l - and dl -leucines indicates that N-acetyl- d -leucine is devoid of any activity.

Publisher Summary This chapter discusses the tropane alkaloids. The rich field of the tropane alkaloids has been investigated intensively in the last five years. The main features of this research work may be summarized: (I) The steric structures of the naturally occurring representatives have been elucidated; (2) the total syntheses of scopolamine, oscine, valeroidine, and dihydrometeloidine serve as conclusive evidence for their structures; (3) the structure suggested for dioscorine in 1950 seems invalidated by more recent experimental facts; (4) a number of synthetic derivatives of the tropeines involving their pharmacological essays have been presented; the problem of biogenesis of the naturally occurring tropanes has been attacked from new angles. The steric course of the reduction of tropinone using a variety of reagents has been extensively studied.

INVESTIGATIONS of the relationships between the anti-tussive activity and other pharmacological properties of many known drugs1 led us to conclude that local anaesthetic effect was very important in order to predict the antitussive activity of new compounds, especially if this action is accompanied by other pharmacological effects such as the antispasmodic and antihistaminic ones. A systematic investigation was then carried out on new synthetic derivatives possessing local anaesthetic properties in different degrees. The compound N (2-benzoyloxy-methyl-2-phenylbutyl)-N,N dimethylamine (benzobut-amine)2 was found to have the most interesting anti-tussive activity among a series of many other related compounds. Benzobutamine displays local anaesthetic properties and, at the same time, shows antispasmodic, anticonvulsant and antihistaminic effects. In this communication a description of the pharmacological properties of this drug is given.

FOR MANY years penicillin has been known to be neurotoxic when injected intrathecally or when applied directly to the brain. 1,2 Yet, few appear to realize that large doses of intravenously administered penicillin may, under certain circumstances, lead to epileptoid convulsions. The current trend to administer penicillin and its synthetic derivatives in ever-increasing doses for treatment of severe infections, or even for prophylactic purposes, exposes some patients receiving such therapy to the hazards of penicillin-induced epilepsy. It would, therefore, seem opportune to report such occurrences in order to increase the awareness of this dangerous complication. We present our experience with five cases in which penicillin had a toxic effect on the cerebrum. Report of Cases Case1.—A 21-year-old man underwent replacement of the mitral and aortic valves with a disposable bubble oxygenator. Total time for cardiopulmonary bypass was 234 minutes. Plasma hemoglobin value at the termination of the extracorporeal circulation