16-16-dimethylprostaglandin-e2 and Hypertension--Renal

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.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Antihypertensive Agents; Chemical Phenomena; Chemistry; Dogs; Drug Stability; Female; Hemodynamics; Hypertension, Renal; Kidney; Male; Muscle Contraction; Prostaglandins A, Synthetic; Prostaglandins E, Synthetic; Rats; Structure-Activity Relationship