PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Spiro Compounds”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed1995

RK-682, a potent inhibitor of tyrosine phosphatase, arrested the mammalian cell cycle progression at G1phase.

A specific inhibitor of protein tyrosine phosphatase (PTPase), RK-682 (3-hexadecanoyl-5-hydroxymethyl-tetronic acid) was isolated from microbial metabolites. In vitro, RK-682 inhibited dephosphorylation activity of CD45 and VHR with IC50 54 and 2.0 microM, respectively. In situ, sodium orthovanadate and RK-682 enhanced the phosphotyrosine level of Ball-1 cells, a human B cell leukemia, but not the phosphoserine/threonine level. The PTPase inhibitors, however, had the different arrest point on the cell cycle progression. Sodium orthovanadate inhibited the cell cycle progression at G2/M boundary phase, on the other hand, RK-682 inhibited the G1/S transition.

Aniline Compounds↗
PubMed2004

Synthesis and antimalarial activity of a new series of trioxaquines.

Trioxanes 8a-b, easily accessible in two steps from allylic alcohol 6a-b, on reductive amination with 4-aminoquinolines 4a-c furnish a new series of trioxaquines 9a-b, 10a-b, 11a-b in 32-77% yields. Dicitrate salts of these trioxaquines have been evaluated for antimalarial activity against multidrug resistant Plasmodium yoelii in mice model.

Aminoquinolines↗
PubMed2004

Deoxypreussomerins from Jatropha curcas: are they also plant metabolites?

Three deoxypreussomerins, palmarumycins CP1, JC1 and JC2, have been isolated from a collection of the stems of Jatropha curcas. The second and third compounds are antibacterial constituents which were characterized from spectral evidence. The X-ray crystallographic structure of palmarumycin JC1 was also studied. Deoxypreussomerins have been obtained here from a plant source in appreciable quantities.

Animals↗
PubMed2003

Identification of a broad-spectrum azasordarin with improved pharmacokinetic properties.

The synthesis and antifungal activity of 5'- and 5'-6'-substituted azasordarin derivatives are described. Modification of the 5'-position led to the discovery of the spirocyclopentyl analogue 7g, which is the first azasordarin to register single-digit MIC values versus Aspergillus spp. Further investigation identified the 5'-i-Pr derivative 7b, which displays superior pharmacokinetic properties compared to other azasordarins.

Administration, Oral↗
PubMed2002

Highly diastereoselective nitrone cycloaddition onto a chiral ketene equivalent: asymmetric synthesis of cispentacin.

[reaction: see text] A highly diastereoselective intramolecular nitrone cycloaddition onto a chiral ketene equivalent, obtained by Horner-Wadsworth-Emmons olefination of either enantiomer of bis-sulfinyl phosphonate 6, is described. Cycloaddition gave 5,5-disubstituted isoxazolidine 10 in good yield as a single diastereomer. Catalytic hydrogenolysis of 10 furnished either enantiomer of optically pure cis-2-aminocyclopentane-1-carboxylic acid.

Antifungal Agents↗
PubMed2004

Diversity-oriented synthesis of azaspirocycles.

Multicomponent condensation of N-diphenylphosphinoylimines, alkynes, zirconocene hydrochloride, and diiodomethane provides a rapid access to omega-unsaturated dicyclopropylmethylamines. These novel building blocks are converted into heterocyclic 5-azaspiro[2.4]heptanes, 5-azaspiro-[2.5]octanes, and 5-azaspiro[2.6]nonanes by means of selective ring-closing metathesis, epoxide opening, or reductive amination. The resulting functionalized pyrrolidines, piperidines, and azepines are scaffolds of considerable relevance for chemistry-driven drug discovery.

Aza Compounds↗
PubMed2001

Synthesis of a 2,9-dioxabicyclo[3.3.1]nonane via double intramolecular hetero-Michael addition: entry to the F-G ring system of the azaspiracids.

[structure: see text]. An effective approach to form a 1,3-disubstituted 2,9-dioxabicyclo[3.3.1]nonane system representing the core of the F and G rings (C28-C34) of the azaspiracid natural products has been developed. The double intramolecular hetero-Michael addition (DIHMA) of a diol upon an ynone generated the bicyclic ketal in a highly diastereoselective fashion.

Alkanes↗
PubMed2005

An efficient and enantioselective approach to the azaspirocyclic core of alkaloids: formal synthesis of halichlorine and pinnaic acid.

A novel, highly stereoselective synthesis of an azaspirocyclic core, which contains four stereogenic carbons consistent with structures of natural halichlorine and pinnaic acid, is presented. Lipase PS-catalyzed selective acylation, asymmetric methylation on the alpha-methylene of the bicyclic lactone, and an asymmetric Michael addition of the tertiary nitro cyclopentane were concisely used to conquer the challenging problem of successfully constructing the C9 quarternary carbon center with complete stereocontrol. The spiropiperidine ring was formed by reduction of the delta-nitroketone, intramolecular condensation, and then highly stereoselective reduction of the cyclic nitrone with NaBH(4). This spirocyclic core is a key intermediate in Danishefsky's synthesis of pinnaic acid and halichlorine.

Alkaloids↗
PubMed1999

Sporovexins A-C and a new preussomerin analog: antibacterial and antifungal metabolites from the coprophilous fungus Sporormiella vexans.

Sporovexins A-C (1-3) and 3'-O-desmethyl-1-epipreussomerin C (4) have been isolated from liquid cultures of the coprophilous fungus Sporormiella vexans (JS 306). The structures of these new metabolites were elucidated on the basis of MS and NMR analysis. Compounds 1 and 4 show antifungal activity against competitor fungi, as well as antibacterial effects.

Anti-Infective Agents↗
PubMed2005

Synthesis of the ABC fragment of the pectenotoxins.

[reaction: see text] A highly stereocontrolled synthesis of the C1-C16 ABC spiroacetal-containing fragment 5 of PTX7 (4) has been achieved. Appendage of the C ring to the AB fragment involved Wittig reaction of spiroacetal aldehyde 8 with a stabilized ylide 9 followed by displacement of allylic iodide 27 with a lithium acetylide to afford enyne 7. Fructose-derived chiral dioxirane and dihydroxylation were then used to introduce the correct functionality in the tetrahydrofuran C ring.

Animals↗
PubMed1989

Highly conformationally constrained halogenated 6-spiroepoxypenicillins as probes for the bioactive side-chain conformation of benzylpenicillin.

The halogenated 6-spiroepoxypenicillins are a series of novel semisynthetic beta-lactam compounds with highly conformationally restricted side chains incorporating an epoxide. Their biological activity profiles depend crucially on the configuration at position C-3 of that epoxide. In derivatives with aromatic-containing side chains, e.g., anilide, the 3R-compounds possess notable Gram-positive antibacterial activity and potent beta-lactamase inhibitory properties. The comparable 3S-compounds are antibacterially inactive, but retain beta-lactamase inhibitory activity. Using the molecular simulation programs COSMIC and ASTRAL, we attempted to map a putative, lipophilic accessory binding site on the PBPs that must interact with the side-chain aromatic residue. Comparative computer-assisted modelling of the 3R-, and 3S-anilides, along with benzylpenicillin, indicated that the available conformational space at room temperature for the side chains of the 3R- and the 3S-anilides was mutually exclusive. The conformational space for the more flexible benzylpenicillin could accommodate the side chains of both the constrained penicillin derivatives. By a combination of van der Waals surface calculations and a pharmacophoric distance approach, closely coincident conformers of the 3R-anilide and benzylpenicillin were identified. These conformers must be related to the antibacterial, 'bioactive' conformer for the classical beta-lactam antibiotics. From these proposed bioactive conformations, a model for the binding of benzylpenicillin to the PBPs relating the three-dimensional arrangement of a putative lipophilic S2-subsite, specific for the side-chain aromatic moiety, and the 3 alpha-carboxylate functionality is presented.

Epoxy Compounds↗