A quantitative reexamination of structure-activity relationships in the delta6-6-substituted progesterone series

J Med Chem. 1974 Aug;17(8):898-900. doi: 10.1021/jm00254a025.

Abstract

PIP: 14 6-substituted-Delta6-16-methylene-17alpha-hydroxy-4,6-prenadiene-3, 20-dione 17-acetate derivatives were analyzed by multiparameter regression techniques for quantitative structure-activity relationships. The parameters were published values for hydrophobic bonding power (pi), inductive effect (F), resonance effect (R), and molar refraction of the substituent (MR); the activity was progestational activity by Clauberg test. Least squares analysis showed that pi gave the best fit with single parameters. With 2 parameters, pi and F accounted for 69% of the variance. F and pi squared gave the best 3-term results, suggesting that pi values up to .50 permit the maximum progestational activity, but perhaps larger substituents decrease activity. The 6-methyl derivative was an exception, having 4 standard deviations' higher activity than computed by the 3-term equation, pointing to unusual metabolism.

MeSH terms

  • Ketosteroids / chemical synthesis
  • Kinetics
  • Pregnadienes / chemical synthesis*
  • Progesterone*
  • Progestins / chemical synthesis*
  • Regression Analysis
  • Structure-Activity Relationship

Substances

  • Ketosteroids
  • Pregnadienes
  • Progestins
  • Progesterone