RESUMO
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.
Assuntos
Androstadienos/química , Androstadienos/síntese química , Gonanos/síntese química , Compostos Radiofarmacêuticos/síntese química , Sítios de Ligação , Gonanos/química , Radioisótopos do Iodo/química , Marcação por Isótopo , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinase/química , Fosfatidilinositol 3-Quinase/metabolismo , Tomografia por Emissão de Pósitrons , Estrutura Terciária de Proteína , Compostos Radiofarmacêuticos/química , WortmaninaRESUMO
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.
Assuntos
Desogestrel/síntese química , Gonanos/química , Cristalografia por Raios X , Gonanos/síntese química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Modelos Moleculares , Conformação Molecular , Estrutura MolecularRESUMO
[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.
Assuntos
Álcoois/síntese química , Alcinos/química , Gonanos/síntese química , Cetonas/síntese química , Compostos Policíclicos/síntese química , Propanóis/química , Álcoois/química , Estrutura MolecularRESUMO
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.
Assuntos
Progestinas/antagonistas & inibidores , Fenômenos Químicos , Química , Estrenos/síntese química , Gonanos/síntese química , MifepristonaRESUMO
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.
Assuntos
Gonanos/síntese química , Congêneres da Progesterona/síntese química , Animais , Fenômenos Químicos , Química , Feminino , Gonanos/metabolismo , Gonanos/farmacologia , Norgestrel/farmacologia , Congêneres da Progesterona/metabolismo , Congêneres da Progesterona/farmacologia , Coelhos , Contração Uterina/efeitos dos fármacosRESUMO
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.
Assuntos
Gonanos/síntese química , Hipolipemiantes/síntese química , Animais , Colesterol/sangue , Clofibrato/farmacologia , Feminino , Hipercolesterolemia/induzido quimicamente , Hipercolesterolemia/fisiopatologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Propiltiouracila , Ratos , Triglicerídeos/sangue , Útero/anatomia & histologia , Útero/efeitos dos fármacosAssuntos
Anticoncepcionais Sintéticos Pós-Coito/síntese química , Anticoncepcionais Pós-Coito/síntese química , Esteroides/síntese química , Androstenos/síntese química , Animais , Cricetinae , Estrenos/síntese química , Feminino , Gonanos/síntese química , Mesocricetus , Gravidez , Relação Estrutura-AtividadeRESUMO
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.