Synthesis and evaluation for uterotrophic and antiimplantation activities of 2-substituted estradiol derivatives.
TL;DR: Two novel series of 2-substituted estradiol derivatives have been synthesized and evaluated for uterotrophic and antiimplantation activities, finding that nuclear substitution at the C-2 position of the steroid nucleus is markedly inhibitory for estrogenic activity.
About: This article is published in Steroids.The article was published on 1992-04-01. It has received 16 citations till now.
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Patent•
02 Aug 1994
TL;DR: The application discloses methods of treating mammalian diseases characterized by abnormal cell mitosis by administering estradiol derivatives including those comprising colchicine or combretastatin A-4 structural motifs as discussed by the authors.
Abstract: The application discloses methods of treating mammalian diseases characterized by abnormal cell mitosis by administering estradiol derivatives including those comprising colchicine or combretastatin A-4 structural motifs of the general formulae found below in a dosage sufficient to inhibit cell mitosis. The application discloses novel compounds used in the methods.
83 citations
Patent•
01 Nov 1999
TL;DR: In this article, amino acid sequences of endostatin proteins and nucleic acid sequences coding for endatin proteins are provided, and compositions capable of inhibiting endothelial cell proliferation, inhibiting angiogenesis and causing tumor regression are described.
Abstract: Endostatin compositions capable of inhibiting endothelial cell proliferation, inhibiting angiogenesis and causing tumor regression are described. Specifically, amino acid sequences of endostatin proteins and nucleic acid sequences coding for endostatin proteins are provided.
28 citations
TL;DR: Among the products, the 2-(4'-methoxyphenyl)-7-methoxy-4H-1-benzopyran-4-one exhibited the highest antiestrogenic activity of 65%. It also elicited 31% of the uterotrophic activity of estradiol.
24 citations
TL;DR: Nuclear modifications included a variety of substituents at the 2 position of estradiol, which was previously thought to be inhibitory for activity, and inclusion of the 3-phenolic hydroxyl group in a γ-pyrone and 3′-formylchromone rings fused to ring A of Estradiol.
22 citations
TL;DR: A series of steroidal 1,4‐diketone derivatives synthesized by acid‐catalyzed condensation of 2‐acetylestradiol‐17β‐acetate with substituted phenylglyoxals displayed uterotrophic activity, antiestrogenic activity, and antifertility activities in mature female albino rats.
Abstract: A series of steroidal 1,4-diketone derivatives was synthesized by acid-catalyzed condensation of 2-acetylestradiol-17 beta-acetate with substituted phenylglyoxals. Conversion of the products into the corresponding pyridazine derivatives was achieved by reaction with hydrazine hydrate. The synthesized compounds were evaluated for their uterotrophic, antiuterotrophic, and antifertility activities in mature female albino rats. Among the compounds tested, the phenyl 2, p-bromophenyl 3, and p-methoxyphenyl 5 diketone derivatives displayed uterotrophic activity of 72%, 72%, and 91%, respectively. The gradation of antiestrogenic activity was assessed in vivo by the inhibition of the estrone-stimulated uterine growth. Compounds 2-5 showed moderate antiestrogenic activity of 53-56%. None of the tested compounds elicited antifertility activity as assessed by the post-coital antiimplantation activity test.
12 citations
References
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TL;DR: It was found that with few exceptions relative binding affinity paralleled uterotropic activity and may be used to determine estrogenic potency, though it must be borne in mind that binding does not distinguish between estrogens and competitive inhibitors.
325 citations
TL;DR: The importance of 2-hydroxyestrone as a product of the metabolism of estradiol in man is discussed and the substantial losses of this metabolite in the various stages of isolation from urine have been estimated.
Abstract: The importance of 2-hydroxyestrone as a product of the metabolism of estradiol in man is discussed. The substantial losses of this metabolite in the various stages of isolation from urine have been estimated.
91 citations
TL;DR: Several tetrahydropyranyl ethers derived from oestradiol and synthetic steroids lacking a 3, or a 17 oxygen function showed a separation on these two parameters; this may indicate a relatively effective antifertility agent with low oestrogenicity.
Abstract: Antifertility activity of fifty-three steroids was studied in the adult, mated female rat. The steroids were given daily for 7 days beginning on the day of pro-oestrus. On Day 9 of the test implantation sites were counted. In most cases the antifertility activity was correlated with oestrogenic activity. Several tetrahydropyranyl ethers derived from oestradiol and synthetic steroids lacking a 3, or a 17 oxygen function showed a separation on these two parameters; this may indicate a relatively effective antifertility agent with low oestrogenicity.
75 citations
TL;DR: A series of 17-substituted, 17-desoxyestratrienes have been synthesized and tested as potential postcoital antifertility agents, and the 17 beta-ethyl side chain exhibited the greatest antif fertility activity with the largest separation ratio to estrogenicity.
Abstract: A series of 17-substituted, 17-desoxyestratrienes have been synthesized and tested as potential postcoital antifertility agents. Estrogen-relative binding affinities were determined, in vivo assays for estrogenic and postcoital antifertility activity were conducted in rats, and selected candidate compounds were further tested for estrogenic activity in monkeys. In the rat, the 17-desoxyestratriene derivatives 8a, 8b, and 30 have shown low estrogenic activity while retaining potent antifertility activity. Structural modifications at the outset included a variety of 17-substituents and an omission of the 17-oxygen functionality, which was previously thought to be necessary for potent activity. The 17 beta-ethyl side chain exhibited the greatest antifertility activity with the largest separation ratio to estrogenicity. Nuclear modification of 17-desoxyethylestrane derivatives at positions 7 and 11 further increased the desired separation of activity, with the 11-hydroxy moiety enhancing separation more than other features.
73 citations
TL;DR: By the synthesis described both the 2- and 4-hydroxylated estrogens are available in high yields.
61 citations