RESUMEN
An improved method for the synthesis of 17ß-hydroxy-16α-iodo-wortmannin along with the first synthesis of 17ß-hydroxy-16α-iodoPX866 and [(131)I] radiolabeled 17ß-hydroxy-16α-[(131)I]iodo-wortmannin, as potential PET tracers for PI3K was also described. The differences between wortmannin and its iodo analogue were compared by covalently docking each structure to L833 in PI3K.
Asunto(s)
Androstadienos/química , Androstadienos/síntesis química , Gonanos/síntesis química , Radiofármacos/síntesis química , Sitios de Unión , Gonanos/química , Radioisótopos de Yodo/química , Marcaje Isotópico , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasa/química , Fosfatidilinositol 3-Quinasa/metabolismo , Tomografía de Emisión de Positrones , Estructura Terciaria de Proteína , Radiofármacos/química , WortmaninaRESUMEN
X-ray crystallographic studies performed on the product of the ketalization reaction of 13beta-ethyl-11alpha-hydroxy-gon-5-ene-3,17-dione have lead to the unequivocal assignment of the 10alpha stereochemistry to C10, showing that an inversion of configuration occurred during formation of the 3,17-diketal. From the Swern oxidation of this compound, 11alpha-(methylthio)methoxy-10alpha-gonene was obtained as the major product instead of the desired 11-ketone. Modeling studies showed that the configurational instability at C10 is determined by the presence of the 11alpha-hydroxyl group.
Asunto(s)
Desogestrel/síntesis química , Gonanos/química , Cristalografía por Rayos X , Gonanos/síntesis química , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Modelos Moleculares , Conformación Molecular , Estructura MolecularRESUMEN
[reaction: see text] Treatment of propargylic diols 5-7 with thionyl chloride promoted a cascade sequence of reactions leading to dichlorides 10-12 and, after reduction with tributyltin hydride, the diindeno-fused 4H-cyclopenta[def]phenanthrenes 13-15 in a single operation. Hydrolysis of 13 and 14 furnished 4H-cyclopenta[def]phenanthren-4-ones 16 and 17, respectively. Air oxidation of an alkaline solution of dichloride 11 produced diketone 18.
Asunto(s)
Alcoholes/síntesis química , Alquinos/química , Gonanos/síntesis química , Cetonas/síntesis química , Compuestos Policíclicos/síntesis química , Propanoles/química , Alcoholes/química , Estructura MolecularRESUMEN
The discovery of the first competitive progesterone antagonist RU 38,486 has initiated an intense search for more potent and more selective anti-progestins. Among several hundreds of compounds under preliminary investigation, biological characterization is most advanced for derivatives RU 38,486, ZK 98,734 and ZK 98,299. These compounds do not only differ in relative potency, but are clearly distinguished by their different behaviour in various animal models. Emphasis is laid on the synthetic problems associated with chemical operations in a sterically crowded environment as represented by structures RU 38,486 and ZK 98,299.
Asunto(s)
Progestinas/antagonistas & inhibidores , Fenómenos Químicos , Química , Estrenos/síntesis química , Gonanos/síntesis química , MifepristonaRESUMEN
The synthesis of new gona-4,9(10)-dienes with a 17 alpha-CH2X-substituent (X = CN, N3, Cl or Br) is described. The progestagenic activity of these substances was studied in the McPhail assay using immature rabbits. The compound XVI (X = CN, STS 557) is the most potent one, showing an activity about ten times higher than D-norgestrel. Differences in the activity caused by different routes of application are discussed.
Asunto(s)
Gonanos/síntesis química , Congéneres de la Progesterona/síntesis química , Animales , Fenómenos Químicos , Química , Femenino , Gonanos/metabolismo , Gonanos/farmacología , Norgestrel/farmacología , Congéneres de la Progesterona/metabolismo , Congéneres de la Progesterona/farmacología , Conejos , Contracción Uterina/efectos de los fármacosRESUMEN
Numerous aryloxy derivatives containing a lipophilic group have been found to possess hypolipidemic activity. This has prompted the preparation of various derivatives of 3-hydroxy-17,17-dimethylgona-1,3,5(10),8,11,13-hexaene (6a). In 6a the lipophilic biphenyl group is incorporated into the steroid nucleus. A three-step synthesis of 6a from 17beta-methylestradiol methyl ether was developed. The derivatives prepared were tested in rats made hypercholesterolemic with propylthiouracil. Several were found active in this test.
Asunto(s)
Gonanos/síntesis química , Hipolipemiantes/síntesis química , Animales , Colesterol/sangre , Clofibrato/farmacología , Femenino , Hipercolesterolemia/inducido químicamente , Hipercolesterolemia/fisiopatología , Masculino , Tamaño de los Órganos/efectos de los fármacos , Propiltiouracilo , Ratas , Triglicéridos/sangre , Útero/anatomía & histología , Útero/efectos de los fármacosAsunto(s)
Anticonceptivos Sintéticos Poscoito/síntesis química , Anticonceptivos Poscoito/síntesis química , Esteroides/síntesis química , Androstenos/síntesis química , Animales , Cricetinae , Estrenos/síntesis química , Femenino , Gonanos/síntesis química , Mesocricetus , Embarazo , Relación Estructura-ActividadRESUMEN
13beta-Ethyl-3-methoxy-17beta-ol-8,14-seco-1,3,5(10),8-gonatetraen-14-one (IIIa) was isolated and its participation in the well-known acidic cyclization process was established.
