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Androgen Receptor Antagonists (androgen + receptor_antagonist)
Selected AbstractsChemInform Abstract: Synthesis and Biological Evaluation of Amino-Pyridines as Androgen Receptor Antagonists for Stimulating Hair Growth and Reducing Sebum Production.CHEMINFORM, Issue 4 2008Lain-Yen Hu Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] N-Arylpiperazine-1-carboxamide Derivatives: A Novel Series of Orally Active Nonsteroidal Androgen Receptor Antagonists.CHEMINFORM, Issue 38 2005Isao Kinoyama Abstract For Abstract see ChemInform Abstract in Full Text. [source] The Synthesis and Evaluation of [2.2.1]-Bicycloazahydantoins as Androgen Receptor Antagonists.CHEMINFORM, Issue 16 2005Aaron Balog Abstract For Abstract see ChemInform Abstract in Full Text. [source] Flutamide inhibits nifedipine- and interleukin-1,-induced collagen overproduction in gingival fibroblastsJOURNAL OF PERIODONTAL RESEARCH, Issue 4 2010H.-K. Lu Lu H-K, Tseng C-C, Lee Y-H, Li C-L, Wang L-F. Flutamide inhibits nifedipine- and interleukin-1,-induced collagen overproduction in gingival fibroblasts. J Periodont Res 2010; 45: 451,457. © 2010 John Wiley & Sons A/S Background and Objective:, To understand the role of the androgen receptor in gingival overgrowth, the effects of flutamide on interleukin-1,- and nifedipine-induced gene expression of connective tissue growth factor (CTGF/CCN2) and collagen production in gingival fibroblasts were examined. Material and Methods:, Gingival fibroblasts from healthy subjects and patients with dihydropyridine-induced gingival overgrowth (DIGO) were used. Confluent cells were treated with nifedipine, interleukin-1, or both. The mRNA expression was examined using real-time polymerase chain reaction, and the concentration of total soluble collagen in conditioned media was analysed by Sircol Collagen Assay. In addition, the protein expressions of androgen receptor, CTGF/CCN2 and type I collagen in gingival tissue were determined by western blot. Results:, Interleukin-1, was more potent than nifedipine in stimulating CTGF/CCN2 and procollagen ,1(I) mRNA expression, and there was an additive effect of the two drugs. Healthy cells exhibited an equal or stronger response of procollagen ,1(I) than those with DIGO, but DIGO cells displayed a stronger response in the secretion of soluble collagen in the same conditions. Flutamide, an androgen receptor antagonist, inhibited stimulation by nifedipine or interleukin-1,. Additionally, the protein expressions of androgen receptor and type I collagen were higher in DIGO gingival tissue than those in healthy gingival tissue. Conclusion:, The data suggest that both nifedipine and interleukin-1, play an important role in DIGO via androgen receptor upregulation and that gingival overgrowth is mainly due to collagen accumulation. Flutamide decreases the gene expression and protein production of collagen from dihydropyridine-induced overgrowth cells. [source] Combined exposures to anti-androgenic chemicals: steps towards cumulative risk assessmentINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2010A. Kortenkamp Summary There is widespread exposure to anti-androgens, a group of chemicals able to disrupt androgen action in foetal life, with irreversible de-masculinizing consequences. Substances of concern include certain phthalates, pesticides and chemicals used in cosmetics and personal care products. Although people come into contact with several anti-androgens, chemicals risk assessment normally does not take account of the effects of combined exposures. However, a disregard for combination effects may lead to underestimations of risks and for this reason, we have assessed the feasibility of conducting cumulative risk assessment, where the focus is on considering the effects of exposure to multiple chemicals, via multiple routes and pathways. Following recent recommendations by the US National Research Council, we have, for the first time, included phthalates and other anti-androgenic chemicals, a total of 15 substances. On the basis of exposure estimates for the individual chemicals and reference doses for anti-androgenicity, we have used the hazard index approach. We show that the cumulative risks from anti-androgen exposures exceed acceptable levels for people on the upper end of exposure levels. The value obtained for median exposures to the 15 substances can be judged tolerable. However, significant knowledge gaps exist that prevent us from arriving at definitive conclusions. Of greatest concern is an absence of appropriate in vivo toxicity data about large numbers of in vitro androgen receptor antagonists. Knowledge about the effect profiles of these chemicals will lead to higher risk estimates. Our analysis suggests that risk reductions can be achieved by limiting exposures to the plasticizer diethyl hexyl phthalate, the cosmetic ingredients butyl- and propyl paraben, the pesticides vinclozolin, prochloraz and procymidone and bisphenol A. [source] Combined exposure to anti-androgens causes markedly increased frequencies of hypospadias in the ratINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2008S. Christiansen Summary The incidence of hypospadias is increasing in young boys, but it remains unclear whether human exposure to endocrine disrupting chemicals plays a role. Risk assessment is based on estimation of no-observed-adverse-effect levels for single compounds, although humans are exposed to combinations of several anti-androgenic chemicals. In a mixture (MIX) study with three androgen receptor antagonists, vinclozolin, flutamide and procymidone, rats were gavaged during gestation and lactation with several doses of a MIX of the three chemicals or the chemicals alone. External malformations of the male reproductive organs were assessed on PND 47 using a score from 0 to 3 (normal to marked) for hypospadias. Markedly increased frequencies were observed after exposure to a MIX of the three chemicals compared to administration of the three chemicals alone. Anogenital distance at PND 1, nipple retention at PND 13, and dysgenesis score at PND 16 were highly correlated with the occurrence of hypospadias, and MIX effects were seen at doses where each of the individual chemicals caused no observable effects. Therefore, the results indicate that doses of anti-androgens, which appear to induce no hypospadias when judged on their own, may induce a very high frequency of hypospadias when they interact in concert with other anti-androgens. [source] Structure determination of chiral sulfoxide in diastereomeric bicalutamide derivativesCHIRALITY, Issue 6 2009Wei Li Abstract We report on the synthesis and investigation of two diastereomers (5a and 5b) of a new bicalutamide analog with an asymmetric carbon atom and a chiral sulfoxide group. These bicalutamide analogs are novel androgen receptor antagonists with biological activities that depend significantly on the configuration of their stereogenic centers. We determined the absolute configuration at the SO center by combining X-ray and NMR measurements with quantum chemical calculations. Since 5a and 5b failed to yield satisfactory crystals for X-ray crystal structure determination, analogs 6a and 6b differing in only one remote functional group relative to the chiral sulfoxide were synthesized, which yielded satisfactory crystals. X-ray structure determination of 6a and 6b provided the absolute configuration at the chiral sulfoxide. Since the structural difference between 5 and 6 is remote from the chiral sulfoxide, the structural assignment was extended from the diastereomers of 6 to those of 5 provisionally. These assignments were verified with the help of measured and DFT-calculated proton and carbon NMR chemical shifts. Chirality, 2008. © 2009 Wiley-Liss, Inc. [source] | |||||||||||||