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991.
The solid-phase synthesis of 16-derivatives of 5-androstane-3,17-diol with one, two or three levels of molecular diversity was accomplished using the diethylsilyloxy linker. Libraries with one level of diversity (10 members) and two levels of diversity (40 members) were synthesized in a parallel fashion in good yields and acceptable HPLC purities for the majority of library members. Compounds with three levels of diversity (15 pools) were realized in a split and pool fashion to allow further deconvolution by the positional scanning method. The screening of the generated model libraries revealed interesting preliminary structure–activity relationships related to their antiproliferative activities on androgen-sensitive Shionogi cells. In the case of the two-level library, the presence of a hydrophobic amino acid at R1 (isoleucine (Ile) or phenylalanine (Phe)) and a six-membered ring (aromatic or not) at R2 seems an important requirement for activity. In the three-level library, the amino acid residues isoleucine and phenylalanine clearly provided a better antiproliferative activity than glycine (Gly) and proline (Pro). These model libraries will serve as basis for the generation of larger libraries of peptidosteroids toward the development of therapeutic agents. 相似文献
992.
Lee J Chubb AJ Moman E McLoughlin BM Sharkey CT Kelly JG Nolan KB Devocelle M Fitzgerald DJ 《Organic & biomolecular chemistry》2005,3(20):3678-3685
Currently available non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin are directed at the cyclooxygenase (COX) site, but not the peroxidase (POX) activity of prostaglandin H2 synthase (PGHS). They are thus unable to inhibit the free-radical induced tissue injury associated with PGHS peroxidase activity, which can occur independently of the COX site. A lead compound, anthranilic hydroxamic acid (AHA) was found to have significant PGHS-POX inhibitory activity (IC50= 72 microM). To define the critical parameters for PGHS-POX inhibition, we investigated 29 AHA derivatives, synthesised from their acid precursors, using solid phase synthesis. In vitro analysis demonstrated a ten-fold improvement in inhibition with 3,5-diiodoanthranilic hydroxamic acid (IC50= 7 microM). 相似文献
993.
Denis A. Labutin 《Proceedings of the American Mathematical Society》2000,128(11):3399-3403
For an arbitrary open set we characterize all functions on the real line such that for all . New element in the proof is based on Maz'ya's capacitary criterion for the imbedding . 相似文献
994.
The rates of convergence of iterative methods with standard preconditioning techniques usually degrade when the skew-symmetric part S of the matrix is relatively large. In this paper, we address the issue of preconditioning matrices with such large skew-symmetric parts. The main idea of the preconditioner is to split the matrix into its symmetric and skew-symmetric parts and to invert the (shifted) skew-symmetric matrix. Successful use of the method requires the solution of a linear system with matrix I+S. An efficient method is developed using the normal equations, preconditioned by an incomplete orthogonal factorization.Numerical experiments on various systems arising in physics show that the reduction in terms of iteration count compensates for the additional work per iteration when compared to standard preconditioners. 相似文献
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998.
Marie-Louise Filleux-Blanchard Denis Le Botlan 《Magnetic resonance in chemistry : MRC》1977,9(11):618-620
1H n.m.r. measurements of a series of propenylylideneammonium salts at temperatures varying from ?90 °C to 70 °C reveal the existence of two conformers. Values of chemical shifts and coupling constants are explained by rotation about a carbon–carbon bond; this hypothesis is supported by the 13C n.m.r. results. Free energies of activation are given for various substituents. 相似文献
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1000.