Antihypertensive activity of 16, 16-dimethyl-oxa-alkyl-prostaglandins of the PGA2, PGE2 and trans-delta 2-11-deoxy-PGE1 series: structure-activity relationships.
Utilizing Corey's synthesis, a variety of prostaglandins (PGs) with a modified omega-side chain were prepared. The 16, 16-dimethyl-oxa-alkyl analogues of PGA2 had potent antihypertensive activity. HR 466 (16, 16-dimethyl-18-oxa-PGA2), the best compound out of this series was active for 5-6 hours after oral administration of 0, 1 mg/kg to conscious renal hypertensive dogs. The corresponding analogues of PGE2 were also potent anti-hypertensive compounds, but were much more spasmogenic. Structural variations within the trans-delta 2-11-deoxy-PGE1-series, in both side chains, gave HR 601 (trans-delta2-15alpha-acetoxy-16, 16-dimethyl-18-oxa-11-deoxy-PGE1-methylester) which was orally active in the hypertensive dog with similar activity to HR 466.
D015064:16,16-Dimethylprostaglandin E2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D004355:Drug Stability; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006977:Hypertension, Renal / Q000188:drug therapy; D007668:Kidney / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D011455:Prostaglandins A, Synthetic / Q000494:pharmacology*; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D000959:Antihypertensive Agents; D011455:Prostaglandins A, Synthetic; D011459:Prostaglandins E, Synthetic; D015064:16,16-Dimethylprostaglandin E2