Influence of the position of the side chain hydroxy group on the gastric antisecretory and antiulcer actions of E1 prostaglandin analogs

Dajani, Esam Z.; Driskill, Doyle R.; Bianchi, Robert G.; Collins, Paul W.; Pappo, Raphael

doi:10.1016/s0090-6980(75)80023-2

Cited by 19 publications

(6 citation statements)

References 5 publications

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“…Documentation from the manu facturers claims that misoprostol has fewer gastrointesti nal side effects than other prostaglandins [8,9], Still, available evidence from peroral treatment indicates that this drug has a significant effect on the uterus both in early [ 10] and late pregnancy [ 11 -13]. In addition to the uterine impact shown for misoprostol there are also reports of possible teratogenic effects of the drug [14,15].…”

Section: Discussionmentioning

confidence: 99%

Pregnancy Interruption by Vaginal Misoprostol

Bugalho

Bique

Almeida

et al. 1993

Gynecol Obstet Invest

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A total of 132 pregnant women with average gestational age of 14.2 weeks (range 11–22 weeks) undergoing legal abortion volunteered for a trial utilizing vaginal administration of misoprostol. In 106 women a dose of 800 µg was utilized, whilst in 26 women 1,200-1,600 µg were given. Nonsurgical expulsion of the fetus was successful in 117 cases (88.6%). Four cases had to be excluded for various social reasons. A total of 11 did not achieve fetal expulsion within 56 h after application of misoprostol. These cases (11/132; 8.3%) were considered failures. Previous reports in the literature of toxicity trials on animals reporting no fetotoxic nor teratogenic effects of misoprostol at doses up to 10,000 µg/kg body weight seem to be of no validity in the human since we could demonstrate that almost 80% of pregnancies were interrupted at a dose of 10–15 µg/kg body weight. The conclusion is that vaginal administration of this prostaglandin analogue, not requiring cool temperature for storage, is remarkably effective in achieving safe interruption of pregnancy without any significant complications.

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Section: Discussionmentioning

confidence: 99%

Pregnancy Interruption by Vaginal Misoprostol

Bugalho

Bique

Almeida

et al. 1993

Gynecol Obstet Invest

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“…methyl ester (PGEiME). The parent compound of this series, (±)- 15-deoxy-16a,/3-hydroxyprostaglandin E¡ methyl ester (3), was found to be equipotent to the reference standard PGEiME. Methylation at C-16 of 3 produced 8 which was found to be some 40 times more potent than PGEv In sharp contrast, addition of two methyl groups to 3 at Ci5 or C17 markedly reduced the antisecretory action.…”

mentioning

confidence: 86%

“…In fact, this modification confers oral activity, decreases the typical PGEi side effects, and prolongs biological action. 3 We now wish to report the full experimental details of our work and define some structure-activity relationships (SAR) with respect to gastric antisecretory effects in the dog.…”

mentioning

confidence: 99%

Synthesis and gastric antisecretory properties of 15-deoxy-16-hydroxyprostaglandin E analogs

Collins¹,

Dajani²,

Driskill³

et al. 1977

J. Med. Chem.

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The preparation and gastric antisecretory activity of a series of 15-deoxy-16-hydroxyprostaglandin analogues are described. The compounds were tested intravenously in histamine-stimulated Heidenhain pouch dogs in relation to the reference standards PGE1 and PGE1 methyl ester (PGE1ME). The parent compound of this seris, (+/-)-15-deoxy-16alpha,beta-hydroxyprostaglandin E1 methyl ester (3), was found to be equipotent to the reference standard PGE1ME. Methylation at C-16 of 3 produced 8 which was found to be some 40 times more potent than PGE1. In sharp contrast, addition of two methyl groups to 3 at C15 or C17 markedly reduced the antisecretory action. The 16-ethyl analogue of 3 also showed reduced potency. Removal or epimerization of the C-11 hydroxy group of 8 reduced the activity. Likewise, hydrogenation or changing the stereochemistry of the 13,14 double bond from trans to cis decreased the activity. On the other hand, omega-homologation of 8 or the introduction of a cis-5,6 double bond did not affect the potency. From these studies, it appears that 8, 16, and 17 possess optimum gastric antisecretory effects in this series.

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“…For example, in laboratory animals PGE, produces effects such as trembling, retching, emesis, and diarrhoea. 150 Furthermore, when administered to headache, abdominal cramps, hypotension, hyperthermia, and shivering are observed.…”

Section: Analogues Of Prostaglandin E and Related Compoundsmentioning

confidence: 99%