RESUMO
The syntheses and the pregnancy-terminating activity relationships of compounds -n are reported. Compounds 5b and are found to be more potent than DL-111-a known drug having effective pregnancy-terminating activity in vitro. Further research shows compounds 5b and have the same activity as DL-111 in vivo. We also found an exciting result that they have excellent anti-implantation activity after oral administration.
Assuntos
Abortivos não Esteroides/síntese química , Abortivos não Esteroides/farmacologia , Animais , Desenho de Fármacos , Implantação do Embrião/efeitos dos fármacos , Embrião de Mamíferos/efeitos dos fármacos , Luteólise/efeitos dos fármacos , Luteolíticos/síntese química , Luteolíticos/farmacologia , Camundongos , Piridinas/síntese química , Piridinas/farmacologia , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/farmacologiaRESUMO
An agonist of chicken hypothalamic luteinizing hormone-releasing hormone (cLH-RH), [D-Trp6] cLH-RH, was synthesized and tested for luteinizing hormone (LH)-releasing activity using dispersed chicken anterior pituitary cells, as well as for binding to rat anterior pituitary membrane receptors. cLH-RH and mammalian LH-RH (mLH-RH) gave identical dose-response curves in stimulating chicken LH release (ED50 = 1.6 and 1.8 X 10(-9) M respectively) and similar estimates of potency. The [D-Trp6] analogs of cLH-RH and mLH-RH stimulated LH release at lower doses (ED50 = 7.0 and approximately 7.0 X 10(-11) M respectively) and were approximately 20-fold more potent. In contrast to the activity in the chicken bioassay, cLH-RH bound to rat anterior pituitary membrane receptors with a much lower affinity than did mLH-RH and had a relative potency of 2%. [D-Trp6] cLH-RH was approximately 100-fold more potent than cLH-RH in the rat receptor assay while [D-Trp6] mLH-RH was 28-fold more active than mLH-RH. These data demonstrate that substitution of Gly6 of LH-RH with D-Trp enhances the LH release from chicken pituitary cells to a similar extent to that observed in mammals, and indicate that the approaches used to produce active LH-RH analogs in mammals are likely to be applicable to birds.
Assuntos
Hormônio Liberador de Gonadotropina/análogos & derivados , Luteolíticos/síntese química , Adeno-Hipófise/metabolismo , Animais , Bioensaio , Galinhas , Cromatografia Líquida de Alta Pressão , Hormônio Liberador de Gonadotropina/síntese química , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Liberador de Gonadotropina/farmacologia , Indicadores e Reagentes , Cinética , Hormônio Luteinizante/metabolismo , Adeno-Hipófise/efeitos dos fármacos , Receptores de Superfície Celular , Receptores LHRH , Relação Estrutura-Atividade , Pamoato de TriptorrelinaRESUMO
Prostaglandin analogues in which the alkyl chain attached to C-15 in the natural compounds is replaced by an aryl group have been synthesised. Some of these compounds are potent luteolytic agents and comparisons are drawn between this series and 16-aryloxyprostaglandins.
Assuntos
Prostaglandinas Sintéticas/síntese química , Animais , Cricetinae , Feminino , Técnicas In Vitro , Luteolíticos/síntese química , Métodos , Gravidez , Prostaglandinas Sintéticas/farmacologia , Relação Estrutura-Atividade , Contração Uterina/efeitos dos fármacosRESUMO
The synthesis is described of new 15,15-ethylene ketals of natural prostaglandins and prostaglandin analogues. Especially the crystalline trisamine salt of the 15,15-ethylene ketal of 15-dehydro-16-phenoxy-17,18,19,20-tetranorprostaglandin F2alpha is a very active inducer of luteolysis in laboratory animals and cattle.
