3- and 19-Oximes of 16α,17α-cyclohexanoprogesterone derivatives: Synthesis and interactions with progesterone receptor and other proteins

Левина, И. С.; Pokrovskaya, E. V.; Куликова, Л. Е.; Kamernitzky, A. V.; Качала, В. В.; Смирнов, А. Н.

doi:10.1016/j.steroids.2008.03.003

Cited by 21 publications

(3 citation statements)

References 24 publications

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“…Of reported C 21 steroid derivatives, some steroidal 20-hydroxyimino derivatives were reported as dual inhibitors of CYP 17 (17α-hydroxylase/C17,20-lyase) and 5α-reductase [ 10 , 22 ]. Recently, 3- and 19-oximes of 16α,17α-cyclohexanoprogesterone derivatives were synthesized and evaluated to probe the surfaces of progesterone receptor’s and two other protein ligand binding pockets neighboring to 3- and 19-positions of steroid core [ 23 ]. Furthermore, 3-acetoxy-5α,6α-epoxyprogn-16-en-20-one, which doesn’t have a double bond in the A or B ring [ 18 ] and 6α,7α-epoxy progesterone [ 11 ] were reported to exhibit higher 5AR inhibitory activity than finasteride.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and 5α-Reductase Inhibitory Activity of C21 Steroids Having 1,4-diene or 4,6-diene 20-ones and 4-Azasteroid 20-Oximes

2011

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PurposeA connectome is a comprehensive description of synaptic connectivity for a neural domain. Our goal was to produce a connectome data set for the inner plexiform layer of the mammalian retina. This paper describes our first retinal connectome, validates the method, and provides key initial findings.MethodsWe acquired and assembled a 16.5 terabyte connectome data set RC1 for the rabbit retina at ≈2 nm resolution using automated transmission electron microscope imaging, automated mosaicking, and automated volume registration. RC1 represents a column of tissue 0.25 mm in diameter, spanning the inner nuclear, inner plexiform, and ganglion cell layers. To enhance ultrastructural tracing, we included molecular markers for 4-aminobutyrate (GABA), glutamate, glycine, taurine, glutamine, and the in vivo activity marker, 1-amino-4-guanidobutane. This enabled us to distinguish GABAergic and glycinergic amacrine cells; to identify ON bipolar cells coupled to glycinergic cells; and to discriminate different kinds of bipolar, amacrine, and ganglion cells based on their molecular signatures and activity. The data set was explored and annotated with Viking, our multiuser navigation tool. Annotations were exported to additional applications to render cells, visualize network graphs, and query the database.ResultsExploration of RC1 showed that the 2 nm resolution readily recapitulated well known connections and revealed several new features of retinal organization: (1) The well known AII amacrine cell pathway displayed more complexity than previously reported, with no less than 17 distinct signaling modes, including ribbon synapse inputs from OFF bipolar cells, wide-field ON cone bipolar cells and rod bipolar cells, and extensive input from cone-pathway amacrine cells. (2) The axons of most cone bipolar cells formed a distinct signal integration compartment, with ON cone bipolar cell axonal synapses targeting diverse cell types. Both ON and OFF bipolar cells receive axonal veto synapses. (3) Chains of conventional synapses were very common, with intercalated glycinergic-GABAergic chains and very long chains associated with starburst amacrine cells. Glycinergic amacrine cells clearly play a major role in ON-OFF crossover inhibition. (4) Molecular and excitation mapping clearly segregates ultrastructurally defined bipolar cell groups into different response clusters. (5) Finally, low-resolution electron or optical imaging cannot reliably map synaptic connections by process geometry, as adjacency without synaptic contact is abundant in the retina. Only direct visualization of synapses and gap junctions suffices.ConclusionsConnectome assembly and analysis using conventional transmission electron microscopy is now practical for network discovery. Our surveys of volume RC1 demonstrate that previously studied systems such as the AII amacrine cell network involve more network motifs than previously known. The AII network, primarily considered a scotopic pathway, clearly derives ribbon synapse input from photopic ON and OFF cone bipol...

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Section: Introductionmentioning

confidence: 99%

Synthesis and 5α-Reductase Inhibitory Activity of C21 Steroids Having 1,4-diene or 4,6-diene 20-ones and 4-Azasteroid 20-Oximes

2011

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“…Methods for the addition of extra carbocyclic and heterocyclic rings at C-16 and their influence on the biological activity of the pregnanes have been reported. [148][149][150] The role of glucocorticoids in the treatment of asthma has been reviewed, 151 whilst the use of inhibitors of the 11b-hydroxy steroid dehydrogenase in glucocorticoid metabolism as a treatment for type 2 diabetes has been described. 152 Novel adenylyl cyclase inhibitors based on C-21 phenylsulfonates (e.g.…”

Section: Pregnanesmentioning

confidence: 99%

Steroids: partial synthesis in medicinal chemistry

Hanson

2010

Nat. Prod. Rep.

103

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“…For many years, the preparation of pentacyclic steroids has attracted considerable attention from medicinal and synthetic organic chemists. Further, it is proved that a number of biologically important properties of modified steroids are dependent upon structural features of the steroid D-ring [6][7][8]. Chemical modification of the steroid D-ring provides a way to alter the functional groups, sizes and stereochemistry of the D-ring, and numerous structure-activity relationships have been established by such synthetic alterations.…”

Section: Introductionmentioning

confidence: 99%

The Knoevenagel reactions of pregnenolone with cyanomethylene reagents: Synthesis of thiophene, thieno[2,3-b]pyridine, thieno[3,2-d]isoxazole derivatives of pregnenolone and their in vitro cytotoxicity towards tumor and normal cell lines

2013

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3- and 19-Oximes of 16α,17α-cyclohexanoprogesterone derivatives: Synthesis and interactions with progesterone receptor and other proteins

Cited by 21 publications

References 24 publications

Synthesis and 5α-Reductase Inhibitory Activity of C21 Steroids Having 1,4-diene or 4,6-diene 20-ones and 4-Azasteroid 20-Oximes

Synthesis and 5α-Reductase Inhibitory Activity of C21 Steroids Having 1,4-diene or 4,6-diene 20-ones and 4-Azasteroid 20-Oximes

Steroids: partial synthesis in medicinal chemistry

The Knoevenagel reactions of pregnenolone with cyanomethylene reagents: Synthesis of thiophene, thieno[2,3-b]pyridine, thieno[3,2-d]isoxazole derivatives of pregnenolone and their in vitro cytotoxicity towards tumor and normal cell lines

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