1-(5-Methyl-1-phenyl-4-pyrazolyl)-3-[4-(o-tolyl)-piperazinyl]-1-propanone,a new synthetic antihypertensive agent

Zusammenfassung 1-(5-Methyl-1-phenyl-4-pyrazolyl)-3-[4-(o-tolyl)-piperazinyl]-1-propanone (I; CIBA 1002-Go), senkt an normotonischen und hypertonischen Tieren den Blutdruck. Die Drucksenkung kann auf eine periphere Vasodilatation und eine Hemmung hypothalamischer oder medullärer Vasomotorenzentren bezogen werden. Ausserdem wirkt CIBA 1002-Go adrenolytisch.

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Hydrochloride = CIBA 1002-Go.     

Antihypertensive agents III. Synthesis and antihypertensive activity of 3-[4-(p-fluoro-phenyl)-1,2,3,6-tetrahydro-1-pyridyl]-1-[1-(2-hydroxyethyl)-5-methyl-4-pyrazolyl]-1-propanone

Zusammenfassung 3-[4-(p-Fluorphenyl)-1,2,3,6-te-trahydro-1-pyridyl]-1-[1-(2-hydroxyaethyl)-5-methyl-4-pyrazolyl]-1-propanon (I, CIBA 4416/B-Go) senkt bei normotonischen und hypertonischen Tieren den Blutdruck. Die Drucksenkung kann hauptsächlich auf die periphere Vasodilatation sowie auf die Vasomotorenzentren bezogen werden. Ausserdem wirkt CIBA 4416/B-Go adrenolytisch.

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Previous paper:V. P. Arya, R. S. Grewal, C. L. Kaul, S. P. Ghate, D. V. Mehta andT. George, J. Pharm. Sci.58, 432 (1969).Contribution No. 243 from CIBA Research Centre.     

7-Chloro-3-(4-methyl-1-piperazinyl)-4H-1,2,4-benzothiadiazine-1,1-dioxide a new antihypertensive agent

Summary 7-Chloro-3-(4-methyl-1-piperazinyl)-4H-1,2,4-benzothiadiazine-1,1-dioxide (DU-717) is a new compound having sustained antihypertensive activity in a similar manner to that of hydrochlorothiazide. However, this compound shows neither diuretic nor hyperglycemic effect, being different from those of hydrochlorothiazide or diazoxide.     

[2-(Octahydro-1-azocinyl)-ethyl]-guanidine sulfate (CIBA 5864-SU), a new synthetic antihypertensive agent

Résumé On décrit la chimie et la pharmacologie d'un nouvel agent antihypertenseur.     

Pharmacological studies of a new analgesic,dl-erythro-1-phenyl-2-(o-chlorophenyl)-2-[4-(p-methoxybenzyl)-1-piperazinyl] ethanol dihydrochloride,in experimental animals

Summary dl-Erythro-1-phenyl-2-(o-chlorophenyl)-2-[4-(p-methoxybenzyl)-1-piperazinyl] ethanol dihydrochloride showed orally a definite analgesic activity, without producing the significant morphine-like physical dependence liability, and its analgesic potency was about a half that of codeine and far superior to aminopyrine in experimental animals.     

Pharmacological studies of a new analgesic, dl-erythro-1-phenyl-2-(o-chlorophenyl)-2-[4-(p-methoxybenzyl)-1-piperazinyl] ethanol dihydrochloride, in experimental animals.

dl-Erythro-1-phenyl-2-(o-chlorophenyl)-2-[4-(p-methoxybenzyl)-1-piperazinyl] ethanol dihydrochloride showed orally a definite analgesic activity, without producing the significant morphine-like physical dependence liability, and its analgesic potency was about a half that of codeine and far superior to aminopyrine in experimental animals.     

A potent non-steroidal anti-inflammatory agent: 2-[3-chloro-4(3-pyrrolinyl)phenyl]propionic acid

Zusammenfassung Die Synthese und biologische Prüfung von 2-[3-Chlor-4(3-pyrrolinyl)phenyl]-propionsäure als neuer entzündungshemmender Stoff wird beschrieben.     

Ethyl 6,7-bis(cyclopropylmethoxy)-4-hydroxy-3-quinolinecarboxylate,a potent anticoccidial agent

Zusammenfassung Synthese und Wirkung gengen Coccidia des 6,7-bis(Cyclopropylmethoxy)-4-hydroxy-chinolin-3-carbonsäureäthylesters werden beschrieben.     

The efficacy of a novel compound, (E)-1-(4′-bromo-4-biphenylyl)-1-(4-chlorophenyl)-3-dimethylaminoprop-1-ene againstTrypanosoma cruzi in mice

Summary The biological properties of a novel compound 353C with high activity againstTrypanosoma cruzi, are described. The compound was about 10 times and 20 times more effective than either benznidazole or nifurtimox respectively, in producing radical cure in mice. 353C had a long half-life and showed anti-trypanosomal properties when given to mice at weekly intervals.     

Potentiation of ocular response to adrenaline by 3,3-dimethyl-1-[3-methylaminopropyl]-1-phenylphthalan (Lu 3-010) and a thiophthalan analogue (Lu 5-003): Blockers of catecholamine uptake

Résumé Concernant la durée de l'effet du traitement, le composé Lu 3-010 en combinaison avec l'adrenaline est semblable à la protriptyline, et il est plus actif que Lu 5-003 en ce qui concerne la potentiation de la reaction oculaire provoquée par l'adrenaline. Administrés séparement, les composés Lu 3-010 et Lu 5-003 ont des effets semblables, tandis que la protriptyline est le composé le plus actif. L'accroissement de l'efficacité de ces composés résulte probablement de leur abilité à bloquer le mécanisme de l'incorporation de la catecholamine.

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The author acknowledges the technical assistance of Mrs.S. Schaal, Mrs.C. Wood, MissB. Kawchak and Mrs.B. Sumner. The Lu compounds were gifts from H. Lundbeck and Co. Ltd.     

Synthesis of O1.5-(beta-D-galactopyranosyl) [DMet2, Hyp5] enkephalin amide, a new highly potent analgesic enkephalin-related glycosyl peptide

A new series of O-glycosyl enkephalins has been prepared, following a convergent strategy, with high chemical yields. The galactosyl analogue, O1.5-(beta-D-galactopyranosyl) [DMet2, Hyp5] enkephalin amide proved to be one of the most potent in vivo opioid agonists synthesized up to now.     

Sodium [o-[(2,6-dichlorophenyl)-amino]-phenyl]-acetate (gp 45 840), a new non-steroidal anti-inflammatory agent

Zusammenfassung gp 45 840, das Natriumsalz der [o-[(2,6-Dichlorphenyl)-amino]-phenyl]-essigsäure, besitzt pharmakodynamisch in verschiedenen Testsystemen am Tier eine ausgeprägte anti-inflammatorische, antinociceptive und antipyretische Aktivität. Das Präparat zeigt eine höhere Wirksamkeit als Phenylbutazon und ist ebenso aktiv wie Indomethacin; es übertrifft in seiner akuten therapeutischen Breite die beiden Vergleichspräparate.

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Preliminary results have been reported at the 5th International Congress on Pharmacology 1972.     

5-(Hydroxyimino)-4-methoxy-2-(pivaloylimino)thiazolidine-3 -acetamide, a reduced nitroheterocyclic derivative with potent schistosomicidal properties

The synthesis and antischistosome properties of 5-(hydroxyimino)-4-methoxy-2-(pivaloylimino)thiazolidine-3- acetamide (1) are described. The compound was prepared by reduction of the nitrothiazoline (2) with stannous chloride in methanol, and represents the first example of a reduced nitroheterocyclic compound showing potent schistosomicidal properties. The possible relationship of compounds such as 1 to the as yet unidentified reduced active but toxic entities formed in vivo from nitroheterocyclics like metronidazole is discussed.     

5-(Hydroxyimino)-4-methoxy-2-(pivaloylimino)thiazolidine-3-acetamide,a reduced nitroheterocyclic derivative with potent schistosomicidal properties

Summary The synthesis and antischistosome properties of 5-(hydroxyimino)-4-methoxy-2-(pivaloylimino)thiazolidine-3-acetamide (1) are described. The compound was prepared by reduction of the nitrothiazoline (2) with stannous chloride in methanol, and represents the first example of a reduced nitroheterocyclic compound showing potent schistosomicidal properties. The possible relationship of compounds such as1 to the as yet unidentified reduced active but toxic entities formed in vivo from nitroheterocyclics like metronidazole is discussed.Acknowledgments. The authors are grateful to Dr A. J. Everett and his staff for the physical chemistry measurements, and to Mr G. Dickerson for the antischistosome testing.