The p r e s e n t work is a continuation of r e s e a r c h on the addition of sul fur-conta ining nucleophilic r e agents to unsa tura ted nitro compounds of the indole s e r i e s [1]. We have es tabl i shed that 1 a c e t y l 3 n i t r o vinylindole (I) and 3-ni t rovinyl indole (II) readi ly add m e r c a p t a n s in the p r e s e n c e of catalyt ic amounts o f t r i e thylamine. The stabi l i ty of the a lky l and aey lmercap to der iva t ives of 1 indoly l -2-n i t roe thane so obtained (IIIa-c, IVa-c) v a r i e s f rom case to case . Compounds I I Ia -c , which contain an N-aee ty la ted indole nucleus, can be kept at a t e m p e r a t u r e around 0 ~ for ove r a y e a r without noticeable decomposit ion. The ni t rosulf ides IVa and IVb a r e unstable. They could not be isolated, and the judgment that they had been fo rmed was made f r o m e h r o m a t o g r a m s . The thioether IVc has in te rmedia te stabil i ty. Samples of it a lways contain some nit rovinylindole and thioacet ic acid.

Results of search for new beta-adrenoreceptor blocking agents of different effects are summarized. Derivatives of 4-hydroxyindolyl-3-acetic acid are characterized by a prolonged beta-adrenoblocking effect, cardioselective beta-adrenoblockers were found among derivatives of N,N-bis(2-hydroxy-3-phenoxypropanol)amine, and highly effective "hybrid" beta-,a-adrenoblockers were detected among derivatives of 3(5)-phenoxymethylisoxazolines and 5-phenoxymethyl-1,2,4,-oxadiasoles. Clinical studies of one of the most promising compounds of the latter series named proxodolol showed it to be a highly effective antihypertensive, antianginal, and antiglaucoma drug. Proxodolol is permitted for clinical application. At present it is manufactured as eye drops for decreasing intraocular pressure in glaucoma; its production as a solution for injections for arresting hypertensive crises is starting.

AbstractNitration of the N‐protected 5‐methoxytryptamine (I) with nitric acid in acetic acid gives predominantly the 4‐nitro compound (II), together with the derivatives (III) ‐ (V).

The state of the serotonergic system was studied in adaptation of rats to short-term non-damaging stress actions along with the possibility of protecting the heart of conscious animals against arrhythmias in acute ischemia with the serotonin analogue 4-nitro-5-methoxytryptamine. It was shown that the adaptation resulted in a significant increase in rat midbrain serotonin by 70%. Preliminary administration of the serotonin analogue 3 fold reduced the total duration of arrhythmias and approximately 5 fold--the heart fibrillation rate and the death rate of animals in acute ischemia. The data obtained are in agreement with the idea on the role of stress-limiting systems in prevention of stress-induced and ischemic damages of the organism. They show that protective effects of metabolites of these systems can be successfully reproduced with their synthetic analogues or activators.

It was shown that nitration of 5-methoxy-N-phthalyltryptamine in acetic acid gives principally the 4-nitro derivative. The 4-nitro, 4-amino-, and 4-acetyl-amino-derivatives of 5-methoxy-N-phthalyltryptamine were also prepared.

In experiments on mice a study was made of different substituents in the 4th position of the indole ring of 5-methoxytryptamines (5-MOT) on toxicity and radioprotective efficiency of the compounds of this class. It was shown that the administration of the amino-group to a mexamine molecule increased the preparation toxicity; the nitro-group somewhat diminished the toxic properties, and the acetylamino group did not change 5-MOT toxicity. A 5-MOT derivative with a nitro group possessed the strongest radioprotective action. The radioprotective efficiency of these compounds persisted for 1-2 h.

A preparative method has been developed for obtaining substituted nitrotryptamines from the corresponding nitrophenylhydrazones of γ-phthalimidobutyraldehyde.

Disubstituted tryptamines, containing methyl, methoxy, nitro, and amino groups, chlorine, and bromine in the benzene ring, were synthesized. The influence of substituents on the course of individual stages of synthesis was noted.

AbstractDurch Elektroreduktion der Isonitrosoverbindung (IV) in phosphatgepuffertem wäßrigen Methanol (Anolyt gesättigte Na2SO4‐LÖsung, Glasdiaphragma; Hg‐Kathode, Pt‐Anode) läßt sich in guter Ausb. die Titelverbindung (V) darstellen; (V) liegt wie sein Ethylester (VI) in Lösung im Gleichgewicht mit einem H‐brückenstabilisierten tautomeren Enol des Typs (VII) vor (1H‐NMR‐Spektrum).

AbstractDie Benzoylierung von Phenobarbital (5‐Phenyl‐5‐ ethyl‐barbitursäure) (I) wird technisch so durchgeführt, daß (I) mit Benzoylchlorid (II) in Gegenwart von Pyridin auf 120 ‐ 122°C erwärmt wird, wobei man die gewünschte 1‐Benzoyl‐5‐phenyl‐5‐ethyl‐barbitursäure (Benzonal) (III) mit nur 40% Ausbeute erhält.

The nature of the products of reduction of nitro compounds of the indole series containing a polysulfide chain depends on the length of the latter. In mono- and disulfides only the nitro groups are reduced, and diamino monosulfides and diamino disulfides are formed. In the reduction of the dinitro trisulfide the chain is cleaved and an amino thiol is formed. The reduction of acetylthionitro compounds is accompanied by migration of the S-N bond, as a result of which an acetamido thiol is formed.

AbstractMit Hilfe der NMR‐Spektroskopie wird nachgewiesen, daß die Ester (I) der Nitroindolyl‐acrylsäure bei einer cis‐Stellung von Nitrogruppe und Indolylrest weit stabiler sind als die entsprechenden trans‐Formen.

AbstractDas Indolylmethylenoxazolon (I) gibt bei der Behandlung mit Schwefelwasserstoff das Indolylmethylenthiazolon (II).

Während das Nitrovinylindol (I) in warmer Essigsäure mit Natriumthiosulfat zu einem Sulfonsäuresalz (II) reagiert, entsteht aus der entsprechenden N-Acetylverbindung (III) ein Gemisch von Di- und Tri-sulfiden (IV) und (V).