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 109 records · Page 6Linked to original sources
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↗
PubMed1989

Inhibition of converting enzyme in brain tissue and cerebrospinal fluid of rats following chronic oral treatment with the converting enzyme inhibitors ramipril and Hoe 288.

A direct central nervous system (CNS)-related component of the cardiovascular actions of converting enzyme (CE) inhibitors will be governed by the ability of these drugs to gain access to the brain. We investigated the inhibitory effect of the two CE inhibitors ramipril and Hoe 288 on CE activity in different brain regions and in the cerebrospinal fluid of rats. One-week oral gavage treatment with ramipril (10 mg/kg/day) and Hoe 288 (10 mg/kg/day) resulted in a marked inhibition of CE activity in the brain cortex (90 and 91%, respectively), the hypothalamus (78 and 82%, respectively), and in the brainstem (67 and 66%, respectively). The complete blockade of plasma CE activity was paralleled by a 84% inhibition of CE activity in cerebrospinal fluid. Both CE inhibitors failed significantly to inhibit CE activity in the striatum. Our results demonstrate that the CE inhibitors Hoe 288 and ramipril were able to pass the blood-brain barrier (BBB) to inhibit central CE activity. The penetration of CE inhibitors into the CNS appears to depend on the lipophilicity of the drugs and on the mode of drug application. The possibility that an inhibition of CE activity in circumventricular organs outside the BBB such as the subfornical organ and the organum vasculosum of the lamina terminalis may be sufficient to explain the central effects of orally applied CE inhibitors is discussed.

Administration, Oral↗
PubMed1970

Detection of griseofulvin and dechlorogriseofulvin by thin-layer chromatography and gas-liquid chromatography.

A rapid and accurate method is described for the determination of griseofulvin and dechlorogriseofulvin extracted from Penicillium urticae with chloroform. Thinlayer chromatography was used to tentatively identify griseofulvin or dechlorogriseofulvin, or both. Two gas-liquid chromatographic systems provided additional qualitative information and simultaneous quantitation of the individual compounds.

Chloroform↗
PubMed1992

A new angiogenesis inhibitor, FR-111142.

FR-111142 is a new angiogenesis inhibitor produced by a fungus Scolecobasidium arenarium F-2015. FR-111142 inhibited endothelial cell proliferation in vitro and angiogenesis in the growing chick chorioallantoic membrane model in vivo. Further, FR-111142 also suppressed the solid tumor growth in mice.

Allantois↗
PubMed1992

On the antiviral activity of diffusomycin (oxazolomycin).

The effect of the beta-lactone antibiotic diffusomycin (oxazolomycin) was investigated against vaccinia (Lister), herpes simplex type 1 (Kupka), influenza A (WSN; H1N1), and Coxsackie A9 viruses. Diffusomycin reduced significantly the plaque formation of enveloped DNA and RNA viruses by more than 90% in the range of the maximally tolerated dose. As could be shown with vaccinia virus, the antiviral action was not caused by virucidal effect on virions or by interaction with virus adsorption and penetration. In one-step growth cycle assays diffusomycin prevented the replication of herpes simplex type 1, vaccinia and influenza A viruses in a dose-dependent manner. The replication of influenza A viruses was blocked immediately after addition of the compound during zero to six hr p.i. Partial reversibility of the antiviral action was established by washing off the antibiotic from chicken embryo cells (CEC) infected with influenza A virus. Finally, replication of Coxsackie A9 virus was not inhibited by diffusomycin. Electron-optical studies revealed a reduced synthesis of HSV-1 nucleocapsids in dependence on the concentration of the compound.

Animals↗
PubMed1992

Analogues of the muscarinic agent 2'-methylspiro[1-azabicyclo[2.2.2]octane-3,4'-[1,3]dioxolane]: synthesis and pharmacology.

A number of tetrahydrofuran analogues of 2'-methylspiro[1-azabicyclo[2.2.2]octane-3,4'-[1,3]dioxolane] (1) have been prepared with the aim to obtain information about the relative importance of each of the oxygens in 1 for efficacy and for selectivity. In addition, the dimethyl and desmethyl analogues of 1 were prepared. The new compounds were compared to cis- and trans-1 with regard to their ability to displace (-)-[3H]-3-quinuclidinyl benzilate ((-)-[3H]QNB) from muscarinic receptors in cerebral cortex, heart, parotid gland, and urinary bladder from guinea pigs. Functional studies were made on isolated guinea pig bladder and ileum. The new compounds exhibited both lower affinity and efficacy than cis-1. A conformational study was performed, and the effects of steric and electronic factors on the biological activity of the compounds are discussed.

Animals↗