The deamino derivatives of [4-threonine]-oxytocin and [4-threonine]-mesotocin; Analogs possessing a surprising spectrum of diminished pharmacological activities

Zusammenfassung Synthese (Merrifield-Methode) und pharmakologische Eigenschaften der Desamino-Derivate von (4-Threonin)-Oxytocin und (4-Threonin)-Mesoxytocin werden beschrieben.

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This work was supported in part by the Medical College of Ohio, a Contract (No. 69-2193) from the Center for Population Research of the National Institute of Child Health and Human Development, Research Grants from the National Science Foundation (No. GB-4932), the National Institute of Arthritis and Metabolic Diseases (No. AM-01940) and a General Research Support Grant to Columbia University from the National Institutes of Health. The authors wish to thank Mrs.Sara Crumm for performing the amino acid analyses and Mrs.Margot Acosta for performing the bioassays. An abstract of part of this work was presented at the 2nd American Peptide Symposium, Cleveland, Ohio, August 1970;M. Manning andW. H. Sawyer,Peptides (Ed.Saul Lande, Gordon and Breach, New York 1971), in press.     

Distribution of 4-methoxy-3-indolylmethyl-glucosinolate (4-methoxy-glucobrassicin) in Brassicaceae

Summary 4-methoxy-3-indolylmethyl-glucosinolate was detectable by HPLC-methods in a representative profile of members of the brassicaceae. In many species it proved to be the main glucosinolate present in young seedlings.     

The synthesis of (±)-4-methoxypterocarpin

Zusammenfassung Die Synthese von (±)-4-Methoxypterocarpin aus 7,8-Dimethoxy-4-oxycumarin wird beschrieben.     

Antihypertensive and other cardiovascular effects of 2-(3-pyridyl)- and 2-(4-pyridyl)-4-trifluoromethylimidazoles

Summary 2 new 4-trifluoromethylimidazole derivatives were found which lowered mean arterial pressure in renal and spontaneously hypertensive (SH) rats by the oral route. In SH rats, compounds A and B were 0.1 and 0.3 times, respectively, as potent as hydralazine. No tolerance development was observed in SH rats with either compound over a 1-week period. In anesthetized dogs, both compounds lowered arterial pressure and peripheral vascular resistance but increased cardiac output. By intraarterial administration, both compounds increased femoral arterial blood flow. These findings represent discovery of a new class of vasodilator drugs.Deceased, May 31, 1978.     

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.     

Inhibitors of the acrosomal proteinase acrosin: Human urinary trypsin inhibitor (UTI) and 4-(2-carboxyethyl) phenyl trans 4-aminomethylcyclohexanecarboxylate hydrochloride (DV-1006)

Summary Human urinary trypsin inhibitor (UTI) and (4-(2-carboxyethyl) phenyl trans 4-aminoethylcyclohexanecarboxylate hydrochloride (DV-1006) competitively inhibited the human acrosomal proteinase acrosin; Ki values were 1.2×10^–8M and 9.4×10^–7 M, respectively.     

Antihypertensive and other cardiovascular effects of 2-(3-pyridyl)- and 2-(4-pyridyl)-4-trifluoromethylimidazoles.

2 new 4-trifluoromethylimidazole derivatives were found which lowered mean arterial pressure in renal and spontaneously hypertensive (SH) rats by the oral route. In SH rats, compounds A and B were 0.1 and 0.3 times, respectively, as potent as hydralazine. No tolerance development was observed in SH rats with either compound over a 1-week period. In anesthetized dogs, both compounds lowered arterial pressure and peripheral vascular resistance but increased cardiac output. By intraarterial administration, both compounds increased femoral arterial blood flow. These findings represent discovery of a new class of vasodilator durgs.     

Distribution of 4-iodine-antipyrine (I131) in the rat

Resumen La determinación de agua total y de agua tisular se efectuo por medio de la dilución de 4-yodo-antipirina (I¹³¹) en la rata. Los resultados obtenidos muestran que la distribución regional del indicador no es similar a la del agua, aunque el volumen de agua total encontrado se aproxima a los valores medios normales. Esta distribución del indicador en los tejidos no hace aconsejable la utilización de este indicador para la medición del volumen de agua total o regional.     

Fate of injected 4-Iodoantipyrine (131I) in rats

Résumé Nous avons étudié l'absorption et l'excrétion de l'antipyrine radio-iodée injectée par voie intraveineuse chez le Rat. L'activité incorporée par les différents organes présente deux sommets en fonction du temps. Cette courbe est spécialement significative dans le cas du tractus gastrointestinal. Les analyses chromatographiques des homogénats d'organes montrent une absence complète d'antipyrine radio-iodée au bout de 2 h. Nous n'en avons pas trouvé dans le foie, mÊme après 1 h. Le foie semble responsable de la desiodation. La vie moyenne biologique pour le corps entier est de 4,5 h.     

Composition and efficacy of iodothyronine immunogens and host responsiveness in radioimmunoassay (RIA) for serum thyroxine (T4)

Summary An immunogen was prepared consisting of iodinated and thyroxylated bovine thyroglobulin which on theoretical and practical grouds was highly specific for thyroxine; a rabbit antiserum derived from it fell within limits for RIA specification under conditions wherein a T4-BSA immunogen product was inactive.     

Über Peptidsynthesen,XLIV. Synthese von Ser4-Glu(NH2)8-Oxytocin (Glumitocin)

Summary Ser⁴-Glu(NH₂)⁸-Oxytocin has been synthesized. The identity of the synthetic compound with the neurohypophysal hormone (Glumitocin) recently isolated from species of cartilaginous is demonstrated.

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Über Peptidsynthesen XLIII. Mitteilung,E. Klieger, Experientia23, 620 (1967).