RESUMEN
A new practical synthesis of 17alpha-acetoxy-11beta-(4-N, N-dimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione (CDB-2914) is described. The synthesis gives easily isolable solids at all steps and is amenable to large-scale process.
Asunto(s)
Anticonceptivos Sintéticos Poscoito/síntesis química , Norpregnadienos/síntesis química , Cromatografía en Capa Delgada/métodos , Anticonceptivos Sintéticos Poscoito/aislamiento & purificación , Espectroscopía de Resonancia Magnética/métodos , Norpregnadienos/aislamiento & purificación , Espectroscopía Infrarroja por Transformada de Fourier/métodosRESUMEN
Ether and ester analogues of 2,3-diaryl-2H-1-benzopyrans have been synthesised and tested for their pregnancy inhibiting activity in immature rats. Some of the compounds exhibit potent activity. Structure-activity relationship relative to the hydroxy analogue has been discussed. In general, esters were found to be better inhibitory agents.
Asunto(s)
Benzopiranos/síntesis química , Anticonceptivos Sintéticos Poscoito/síntesis química , Animales , Benzopiranos/farmacología , Anticonceptivos Sintéticos Poscoito/farmacología , Femenino , Masculino , Embarazo , Ratas , Relación Estructura-ActividadRESUMEN
In order to study the relationship between the structure of A-nor-5 alpha-androstane derivatives and their antifertility activity, we designed and synthesized 16 A-nor-5 alpha-androstane compounds through several reaction steps with dehydroepiandrosterone acetate as a starting material. Their structures were confirmed by IR, 1HNMR, MS, elemental analyses, etc. Preliminary pharmacological tests showed that compounds 8, 9, 10 and 16 possess antiimplantation activity to some extent (2.5 mg.kg-1, administered po, gave 67-75% antiimplantation rate). Other compounds showed low activity. The possible relationship between compound structures and their activities is analysed briefly.
Asunto(s)
Anticonceptivos Sintéticos Poscoito/síntesis química , Norandrostanos/síntesis química , Animales , Anticonceptivos Sintéticos Poscoito/farmacología , Implantación del Embrión/efectos de los fármacos , Femenino , Ratones , Ratones Endogámicos ICR , Norandrostanos/farmacologíaRESUMEN
Eleven peptides containing hydroxy-amino-acid have been synthesized manually by stepwise solid-phase method. Three of them were started on BHA-resin, the others on Merrifield-resin. TFMSA/TFA/p-cresol were used as cleaving reagent in all peptide-resin (1-11) cleavage. Furthermore, HF cleaving procedure was also used parallelly to five of those peptide-resins for contrast. No conspicuous difference in yield was found between TFMSA and HF. The purity of all products was checked by the profiles of analytical reversed phase HPLC (C-18) and the data of amino acid analysis. All synthetic peptides were tested for the effect on progesterone production by rat corpus luteum in vitro. Among them, three peptides, GlyTyr-NH2, LysTyr-NH2 and GlySer Lys-OH, showed significant effect (p less than 0.01) on inhibiting hCG-induced progesterone production.
Asunto(s)
Aminoácidos/síntesis química , Anticonceptivos Sintéticos Poscoito/síntesis química , Progesterona/metabolismo , Aminoácidos/farmacología , Animales , Femenino , Células Lúteas/metabolismo , Ratas , Ratas Endogámicas , Relación Estructura-ActividadRESUMEN
Cyclohexanone was condensed with N-hydroxymethyl benzamide in conc. sulphuric acid to give alpha-methyl-benzamido-cyclohexanone (I). The reaction of (I) with thiosemicarbazide in ethanol resulted in alpha-methyl-benzamido-cyclohexanone thiosemicarbazone (II). Condensation of (II) with various aromatic aldehydes in the presence of ethanol afforded alpha-methyl-benzamido-alpha'-substituted-styryl-cyclohexanone thiosemicarbazones (III) in yields ranging from 40 to 50 percent. The compounds exhibited pronounced antiimplantation activity in female albino rats.
Asunto(s)
Anticonceptivos Sintéticos Poscoito/síntesis química , Anticonceptivos Poscoito/síntesis química , Ciclohexanos/síntesis química , Ciclohexanonas/síntesis química , Estirenos/síntesis química , Tiosemicarbazonas/síntesis química , Animales , Benzamidas/administración & dosificación , Benzamidas/síntesis química , Benzamidas/farmacología , Fenómenos Químicos , Química , Ciclohexanonas/administración & dosificación , Ciclohexanonas/farmacología , Implantes de Medicamentos , Femenino , Ratas , Estirenos/administración & dosificación , Estirenos/farmacología , Tiosemicarbazonas/administración & dosificación , Tiosemicarbazonas/farmacologíaRESUMEN
The title diphenol, 1a, was synthesized from p,p'-dihydroxy-alpha-truxillic acid and shown to be active as an oral postcoital antifertility agent in rats: ED100 = 100 (micrograms/kg)/day. The oral uterotropic potency was estimated to be 16% of that of diethylstilbestrol (95% confidence limits of potency 8--35%). The structure of the diphenol, 1a, was confirmed by single-crystal X-ray analysis of the dimethyl ether.
Asunto(s)
Anticonceptivos Sintéticos Poscoito/síntesis química , Anticonceptivos Poscoito/síntesis química , Naftoles/síntesis química , Animales , Antineoplásicos , Fenómenos Químicos , Química , Femenino , Masculino , Naftoles/farmacología , Tamaño de los Órganos/efectos de los fármacos , Ratas , Útero/efectos de los fármacosAsunto(s)
Anticonceptivos Hormonales Poscoito/síntesis química , Anticonceptivos Poscoito/síntesis química , Congéneres del Estradiol/farmacología , Animales , Anticonceptivos Sintéticos Poscoito/síntesis química , Implantes de Medicamentos , Implantación del Embrión/efectos de los fármacos , Congéneres del Estradiol/administración & dosificación , Congéneres del Estradiol/síntesis química , Trompas Uterinas/efectos de los fármacos , Femenino , Fertilidad/efectos de los fármacos , Haplorrinos , Papio , Embarazo , Preñez/efectos de los fármacos , RatasAsunto(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
The 17alpha-ethyl-substituted analogs of the two epimeric 20-dihydroprogesterones, allopregnadedione and pregn-5-ene-3,20-dione, were synthesized and evaluated for their possible oral contragestational (postcoital antifertility) activity in the rat. The compounds, though bound strongly to the progesterone receptor in vitro, were inactive preimplantively at 10 mg/kg and postimplantively at 40 mg/kg in vivo.
PIP: 17alpha-20alpha- and 20beta-dihydroprogesterones and other 17alpha-ethyl-substituted pregnanes as potential contragestational agents were investigated in the rat, and the syntheses of 17 alpha-ethyl-substituted analogs of the 2 epimeric 20-dihydroprogesterones, allopregnanedione and pregn-5-ene-3,20 dione are presented. The compounds were administered orally to 5 rats on Days 1-6 of gestation for studies related to effects on implantation or on Days 9-12 of gestation for studies related to drug effects on pregnancy after implantation. Postmortem examination was carried out between Day 14 and Day 21 of gestation. The compounds were strongly bound to the pr ogesterone receptor in vitro but were inactive preimplantively at 10 mg/kg and postimplantively at 40 mg/kg in vivo.
Asunto(s)
20-alfa-Dihidroprogesterona , Anticonceptivos Sintéticos Poscoito/síntesis química , Anticonceptivos Poscoito/síntesis química , Pregnanos/síntesis química , Progesterona/análogos & derivados , 20-alfa-Dihidroprogesterona/análogos & derivados , 20-alfa-Dihidroprogesterona/síntesis química , 20-alfa-Dihidroprogesterona/metabolismo , 20-alfa-Dihidroprogesterona/farmacología , Animales , Anticonceptivos Sintéticos Poscoito/metabolismo , Anticonceptivos Sintéticos Poscoito/farmacología , Implantación del Embrión/efectos de los fármacos , Femenino , Fertilidad/efectos de los fármacos , Edad Gestacional , Pregnanos/metabolismo , Pregnanos/farmacología , Ratas , Receptores de Superficie Celular , EstereoisomerismoRESUMEN
A series of coumarins and delta3-isoflavenes was prepared. Although antifertility activity was shown by all of these compounds, the required dosage in mice varied from 13.5 mug/kg/day to 50 mg/kg/day. The most potent compounds were the 2-methyl-4-ethylisoflavenes, two of which (2a and 2b) were about equipotent with DES on a molar basis. They were followed by the 2,2-dimethylisoflavenes, the 2-unsubstituted isoflavene, and the coumarins. The most active compounds possessed an acetoxy group at C-7 and an oxygen function at C-4'. Presence of fluorine at C-4' or diethylaminoethoxy at C-M decreased the antifertility activity. The uterotropic activity followed the same trends as the antifertility activity with some evidence for the separation of the two effects in the 2,2-dimethylisoflavene series. Based on a limited study it appears that two phenolic hydroxyl groups are required for the presence of good estrogen receptor binding activity. An apparent lack of correlation between the estrogen binding activity and uterotropic or antifertility effects is probably explained by in vivo metabolism.
Asunto(s)
Cumarinas/síntesis química , Congéneres del Estradiol/síntesis química , Estrógenos no Esteroides/síntesis química , Fertilidad/efectos de los fármacos , Flavonoides/síntesis química , Animales , Sitios de Unión , Unión Competitiva , Anticonceptivos Sintéticos Poscoito/síntesis química , Citosol/metabolismo , Estradiol/metabolismo , Femenino , Flavonoides/farmacología , Ratones , Tamaño de los Órganos/efectos de los fármacos , Ratas , Receptores de Superficie Celular , Útero/efectos de los fármacos , Útero/metabolismoRESUMEN
Three ring beta-secoestradiols, 2alpha,3beta- and 2beta,3beta-2-ethyl-3-(p-hydroxyphenyl)-6beta-methyl-trans-bicyclo[4.3.0]nonan-7beta-ols, have been synthesized and some of them shown to possess significant antiimplantation activity in rats.