ABSTRACT
PIP: The optical isomers of the title compound were synthesized and the biological potencies of the two enantiomers were compared. There was essentially no difference in their hypocholesterolemic activities, as had been predicted, and little or no difference between their uterotropic potencies. The approximately equal uterotropic activities seen with the enantiomers is explained in terms of stereochemical requirements at the receptor level for an estrogenic response. A working model of an estrogenic receptor is proposed. An accompanying paper provides support for the proposed model.^ieng
Subject(s)
Contraceptives, Oral, Synthetic/chemical synthesis , Cyclohexanecarboxylic Acids/chemical synthesis , Animals , Anisoles/chemical synthesis , Anisoles/pharmacology , Anticholesteremic Agents/chemical synthesis , Anticholesteremic Agents/pharmacology , Binding Sites , Cholesterol/blood , Contraceptives, Oral, Synthetic/pharmacology , Cyclohexanecarboxylic Acids/pharmacology , Female , Molecular Conformation , Optical Rotation , Rats , Receptors, Cell Surface/drug effects , Stereoisomerism , Structure-Activity Relationship , Uterus/drug effectsSubject(s)
Contraceptives, Oral, Synthetic/chemical synthesis , Cyclohexanecarboxylic Acids/chemical synthesis , Animals , Anisoles/chemical synthesis , Anisoles/pharmacology , Anticholesteremic Agents/chemical synthesis , Anticholesteremic Agents/pharmacology , Binding Sites , Cholesterol/blood , Contraceptives, Oral, Synthetic/pharmacology , Cyclohexanecarboxylic Acids/pharmacology , Female , Fertility/drug effects , Mice , Models, Biological , Molecular Conformation , Optical Rotation , Organ Size , Rats , Receptors, Cell Surface/drug effects , Stereoisomerism , Structure-Activity Relationship , Uterus/drug effectsSubject(s)
Fibrinolytic Agents/chemical synthesis , Isoquinolines/chemical synthesis , Administration, Oral , Animals , Biological Availability , Blood Coagulation/drug effects , Drug Evaluation, Preclinical , Fibrinolysis/drug effects , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/pharmacology , Isoquinolines/administration & dosage , Isoquinolines/pharmacology , Male , Propylene Glycols , Rats , Structure-Activity RelationshipSubject(s)
Contraceptive Agents/chemical synthesis , Contraceptives, Oral, Synthetic/chemical synthesis , Indenes/chemical synthesis , Alkynes/chemical synthesis , Alkynes/pharmacology , Animals , Contraceptive Agents/pharmacology , Contraceptives, Oral, Synthetic/pharmacology , Contraceptives, Postcoital, Synthetic/pharmacology , Estradiol Congeners/pharmacology , Female , Fertility/drug effects , Indenes/pharmacology , Methylamines/chemical synthesis , Methylamines/pharmacology , Mice , Uterus/drug effectsSubject(s)
Contraceptive Agents/chemical synthesis , Cyclohexanecarboxylic Acids/chemical synthesis , Animals , Anticholesteremic Agents/pharmacology , Cholesterol/blood , Chorionic Gonadotropin/antagonists & inhibitors , Chromatography, Gas , Contraceptive Agents/pharmacology , Cyclohexanecarboxylic Acids/pharmacology , Dogs , Dose-Response Relationship, Drug , Estrogens/pharmacology , Female , Fertility/drug effects , Male , Mice , Organ Size , Prostate/drug effects , Rats , Seminal Vesicles/drug effects , Stereoisomerism , Structure-Activity Relationship , Testis/drug effects , Uterus/drug effectsABSTRACT
PIP: The syntheses of 37 derivatives of 4-methyldibenzothiophene-3carboxylic acid were reported. Compounds were assayed for their estrogenic and antifertility activities in female mice and rats. In general cis isomers were more active than the trans. In certain postcoital dosing regimens, 2 analogs were more active in preventing or terminating pregnancy in rats than would have been predicted on the basis of their estrogenicity. The effectiveness of these 2 compounds in preventing pregnancy was 100 percent when administered on days 1-5 postcoitum in 1 mg. /kg. / day doses to rats. Effectiveness was the same whether administered orally or slbcutaneously.^ieng