Subject(s)
Anti-Inflammatory Agents , Animals , Azides , Biological Assay , Female , Models, Molecular , Molecular Conformation , Rats , Structure-Activity RelationshipSubject(s)
Adrenal Cortex Hormones/chemical synthesis , Azides/chemical synthesis , Progestins/chemical synthesis , Thiocyanates/chemical synthesis , Adrenal Cortex Hormones/pharmacology , Adrenal Glands/drug effects , Androgen Antagonists , Animals , Azides/pharmacology , Female , Male , Molecular Conformation , Muscles/drug effects , Progesterone/pharmacology , Progestins/pharmacology , Prostate/drug effects , Rabbits , Rats , Seminal Vesicles/drug effects , Structure-Activity Relationship , Thiocyanates/pharmacology , Uterus/drug effectsSubject(s)
Norsteroids , Pregnadienes , Androgen Antagonists , Chemical Phenomena , Chemistry , Chlorine , Dealkylation , Ketosteroids/chemical synthesis , Ketosteroids/pharmacology , Norsteroids/chemical synthesis , Norsteroids/pharmacology , Pregnadienes/chemical synthesis , Pregnadienes/pharmacology , Pregnanes , Progestins/pharmacologyABSTRACT
PIP: Synthesis and biological activity of 17-esters of 6-dehydro-16-methylene-17 alpha-hydroxyprogesterone are presented. A systematic study of the influence of the alteration of halogen at 6 and the acyl group at 17 on the progestational and antiandrogenic activities of the resulting structures is described. A convenient general method for synthesis of all of the members of the generic family from the precursors in common is described. It is believed that 6-chloro-16-methylene-17 alpha-hydroxy-4,6-pregnadiene 17-acetate, because of its structural similarity to chlormadinone acetate and its high progestational potency, will perform as a contraceptive at perhaps a lower dose than that of chlormadinone acetate.^ieng
Subject(s)
Hydroxyprogesterones/chemical synthesis , Androgen Antagonists , Animals , Esters/chemical synthesis , Esters/pharmacology , Halogens/chemical synthesis , Hydroxyprogesterones/pharmacology , Magnetic Resonance Spectroscopy , Male , Optical Rotation , Progestins/chemical synthesis , Progestins/pharmacology , Prostate/drug effects , Rabbits , Rats , Rats, Inbred Strains , Seminal Vesicles/drug effects , Spectrum Analysis , Structure-Activity Relationship , Ultraviolet RaysSubject(s)
Pregnanes/chemical synthesis , Progestins/chemical synthesis , Analysis of Variance , Androgen Antagonists , Animals , Female , Fluorine/chemical synthesis , Fluorine/pharmacology , Hydroxysteroids/chemical synthesis , Hydroxysteroids/pharmacology , Ketosteroids/chemical synthesis , Ketosteroids/pharmacology , Magnetic Resonance Spectroscopy , Male , Optical Rotation , Ovary/drug effects , Pregnanes/pharmacology , Progestins/pharmacology , Prostate/drug effects , Rabbits , Rats , Seminal Vesicles/drug effects , Spectrum Analysis , Testis/drug effects , Ultraviolet RaysABSTRACT
PIP: The synthesis of of 6-formyl-6-dehydro-16-methylene-17alpha-acetoxyprogesterone (3) and of 6-cyano-6-dehydro-16-methylene-17alpha-acetoxyprogesterone (4) is reported. The preparation of (3) was carried out by converting 3-ethoxy-16-methylene-17alpha-YDROXY-3,5PREGNADIEN-20-ONE 17-acetate (5) by the Vilsmeier reaction to 3-ethoxy-6-formyl-16-methylene-17alpha-hydroxy-3,5-pregnadien-20-one 17-acetate (6). On treatment with dichlorodicyanobenzoquinone (DDQ) in 95% aqueous acetone (6) afforded the desired (3) in 45% yield. The 6-cyano derivative (4) was prepared by reacting (6) with hydroxylamine to give 3-ethoxy-6-oximinomethyl-16-methylene-17alpha-hydroxy-3, 5-pregnadien-20-one 17-acetate; this compound on treatment with DDQ in 95% aqueous acetone gave 6-oximinomethyl-16-methylene-17alpha-hydroxy-4, 6-pregnadien-3,20-dione 17-acetate (9) in 68% yield. Reaction of (9) with phosphorus oxychloride in pyridine afforded the desired 6-cyano dienone (4) in 70% yield. Progestational activity of (3) was the same as that of progesterone, while that of (4) was 5.8 as great.^ieng