PGA2、PGE2和反式-δ2-11-脱氧-PGE1系列的16,16-二甲基-氧杂-烷基-前列腺素的降压活性：构效关系

Antihypertensive activity of 16, 16-dimethyl-oxa-alkyl-prostaglandins of the PGA2, PGE2 and trans-delta 2-11-deoxy-PGE1 series: structure-activity relationships.

作者信息

Beck G, Bartmann W, Lerch U, Teufel H, Schölkens B

出版信息

Prostaglandins. 1980 Jul;20(1):153-69. doi: 10.1016/0090-6980(80)90015-5.

Abstract

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.

摘要

利用科里合成法，制备了多种具有修饰ω-侧链的前列腺素（PGs）。PGA2的16,16-二甲基-氧杂-烷基类似物具有强大的降压活性。HR 466（16,16-二甲基-18-氧杂-PGA2），该系列中最佳的化合物，对清醒的肾性高血压犬口服0.1mg/kg后活性持续5至6小时。PGE2的相应类似物也是强效降压化合物，但痉挛ogenic性更强。反式δ2-11-脱氧-PGE1系列两侧链的结构变化产生了HR 601（反式δ2-15α-乙酰氧基-16,16-二甲基-18-氧杂-11-脱氧-PGE1-甲酯），其在高血压犬中口服有活性，活性与HR 466相似。