PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Azabicyclo 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 649 records · Page 36Linked to original sources
PubMed1995

Two [7.3.1]azabicyclo-z-3-ene-1,5-diyne analogues of dynemicin A.

The crystal structures of methyl 6-methoxy-17-oxo-2-azatricyclo[7.7.1.0(3,8)]heptadeca-3(8),4 ,6,13-tetraene- 11,15-diyne-2-carboxylate ethyl acetate solvate, (1), 2C19H15NO4.0.5C4H8O2, and tricyclo[3.3.1.1(3,7)]decyl 6-methoxy-17-oxo-2-azatricyclo[7.7.1.0(3,8)]heptadeca-3(8),4 ,6,13-tetraene- 11,15-diyne-2-carboxylate ethyl acetate solvate, (2), C28H27NO4.0.5C4H8O2, are reported. For compound (1), two crystallographically independent molecules are observed. Interestingly, for both compounds (1) and (2), a molecule of ethyl acetate is found in the crystal lattice disordered about an inversion center. The azabicyclo[7.3.1]enediyne core appears to be fairly rigid. Only minor differences are observed in the ring conformation between the two independent molecules in (1) and between compounds (1) and (2) themselves. The conformation is also similar to that found in deoxydynemicin A [Shiomi, Iinuma, Naganawa, Hamada, Hattori, Nakamura, Takeuchi & Iitaka (1990). J. Antibiot. 43, 1000-1005] and triacetyldynemicin A [Konishi, Ohkuma, Tsuno, Oki, Van Duyne & Clardy (1990). J. Am. Chem. Soc. 112, 3715-3716]. The transannular diyne distance (C3...C8) averages 3.428 (2) A for compound (1) and is 3.403 (3) A for compound (2).

Anthraquinones↗
PubMed2006

Using a tritiated compound to elucidate its preclinical metabolic and excretory pathways in vivo: exploring tritium exchange risk.

The metabolism and excretion of N-(3R)-1-azabicyclo[2.2.2]oct-3-ylfuro[2,3-c]pyridine-5-carboxamide (1), an agonist of the alpha7 nicotinic acetylcholinergic receptor, were determined in both Sprague-Dawley rats and beagle dogs using [3H]1. Initially, 3-tritio-furanopyridine 1 ([3H]1a) was evaluated in pilot mass balance studies by determining total radioactivity recovery and pharmacokinetics in lyophilized excreta and nonlyophilized plasma, respectively. Lower mass balance and much greater circulatory radioactivity exposures were observed in rats than in dogs, with urinary tritiated water (HTO) only detected in rats. The 133-h half-life in rats, possibly due to very slowly eliminated metabolites, was more likely attributable to HTO formed from [3H]1a because of site-specific chemical and/or metabolic 3H instability, which was confirmed by urinary HTO. In contrast, dog data supported 3H stability within [3H]1a. Conflicting cross-species data with [3H]1a suggested species-specific metabolic fates for 1, requiring a 3H form of 1 resistant to 3H loss in rats. Therefore, tritiation of 1 at its furanopyridine C7, a site predicted to be both chemically and metabolically stable, yielded 7-tritio-N-(3R)-1-azabicyclo[2.2.2]oct-3-ylfuro[2,3-c]pyridine-5-carboxamide ditrifluoroacetate ([3H]1b), which allowed in both species the determination of all excretory pathways, total radioactivity pharmacokinetics, and major excretory and circulatory metabolites with complete radioactivity recovery without HTO generation. Definitive metabolite elucidation for 1 using [3H]1b confirmed the suspected species-dependent metabolic susceptibility for 3H loss from [3H]1a in rats, but not dogs, since the majority of rat metabolites resulted from furanopyridine biotransformation. The described studies explore the evaluation of tritium exchange risk from a mechanistic biotransformation perspective and highlight the need for careful deliberation when considering and designing 3H compounds for radiolabeled metabolism studies.

Animals↗
PubMed1980

Derivatives of 5,7,7-trimethyl-6-oxa-3-azabicyclo[3.2.2]nonane with antiarrhythmic, local anesthetic and hypotensive activities. I.

The synthesis of three series of 3-acyl-, 3-alkyl- and 3-dialkylaminoacetyl-5,7,7-trimethyl-6-oxa-3-azabicyclo[3.2.2]nonanes, (III), (IV) and (V), respectively, is described. A number of these compounds showed surface anesthesia in rabbits and infiltration anesthesia in mice, and antiarrhythmic activity in guinea pigs and mice, all effects being superior or similar to those of lidocaine. The circulatory, cardiac and respiratory effects in dogs and hens are also described.

Anesthetics, Local↗
PubMed1992

Synthesis and muscarinic activities of quinuclidin-3-yltriazole and -tetrazole derivatives.

The synthesis of 15 methyl or unsubstituted 1,2,3-triazoles, 1,2,4-triazoles, and tetrazoles additionally substituted with a 1-azabicyclo[2.2.2]octan-3-yl group is described. The potency and efficacy of these compounds as muscarinic ligands were determined in radioligand binding assays using [3H]oxotremorine and [3H]quinuclidinyl benzilate. Potency and efficacy were found in compounds in which the azole moiety was attached to the azabicyclic ring either through a carbon atom or a nitrogen atom. Electrostatic potential maps of both the C-linked and the novel N-linked series of compounds were calculated. A relationship between position and depth of the electrostatic minima relative to the azabicyclic ring and the potency and efficacy of the compounds was determined.

Animals↗
PubMed1999

Molecular structures and conformations of three 3-azabicyclononanes.

The structure, conformation, molecular geometry and the mode of packing of 7-tert-butyl-N-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonane (C(25)H(33)N; MTABN), N-acetyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonane (C(22)H(25)NO; AABN) and N-methyl-2,4-bis(2-methylphenyl)-3-azabicyclo[3.3.1]nonan-9-ol (C(23)H(29)NO; MHABN) are presented. The compounds MTABN and MHABN crystallize in monoclinic space groups, whereas AABN is orthorhombic. In each of the three structures, the bicyclic ring system adopts a chair-chair conformation and the phenyl rings are in equatorial orientation with respect to the piperidine ring. In AABN, apart from the van der Waals forces, weak intermolecular C-H.O type interactions are involved in the packing.

Journal Article↗
PubMed1978

A sulfone beta-lactam compound which acts as a beta-lactamase inhibitor.

CP-45,899 [3,3-dimethyl-7-oxo-4-thia-1-azabicyclo(3,2,0)heptane-2-carboxylic acid, 4,4-dioxide [2S-(2alpha,5alpha)]] has low intrinsic activity against most Gram-positive cocci, Enterobacteriaceae and Pseudomonas. It inhibits Neisseria at concentrations of 0.1 approximately 6.2 microgram/ml. The combination of CP-45,899 and ampicillin inhibited Staphylococcus aureus and Enterobacteriaceae resistant to ampicillin by virtue of beta-lactamase activity. Combination of CP-45,899 and cephalothin was synergistic less often, and CP-45,899 did not act synergistically with carbenicillin or ticarcillin against Pseudomonas resistant to these agents. CP-45,899 acted synergistically with ampicillin against Bacteroides. Synergy of CP-45,899 and ampicillin was demonstrated at varying concentrations suggesting that it may significantly enlarge the antibacterial activity of ampicillin against resistant bacteria.

Anti-Bacterial Agents↗
PubMed1980

PS-6 and PS-7, new beta-lactam antibiotics. Isolation, physicochemical properties and structures.

Antibiotics PS-6 and PS-7 which are shown to be 5R,6R-3-(2-acetamido)ethylthio-6-isopropyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene- 2-carboxylic acid and 5R,6R-3-(E)-(2-acetamido) vinylthio-6-ethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid respectively, are new beta-lactam compounds isolated from fermentation broths of Streptomyces cremeus subsp. auratilis A271, S. fulvoviridis A933, S. olivaceus ATCC 31126 and S. flavogriseus NRRL 8139. Fermentation, isolation, physicochemical properties and structures of antibiotics PS-6 and PS-7 are described.

Anti-Bacterial Agents↗
PubMed1991

Quinolone antibacterials: preparation and activity of bridged bicyclic analogues of the C7-piperazine.

A series of quinolone and naphthyridine antibacterial agents possessing as the C7-heterocycle bicyclic 2,5-diazabicyclo[n.2.m]alkanes, where n = 2, 3 and m = 1, 2, and a series including 4-aminopiperidine and 3-amino-8-azabicyclo[3.2.1]octanes have been prepared and evaluated in vitro and in vivo for antibacterial activity against a variety of Gram-negative and Gram-positive organisms. These compounds were also tested against the target enzyme bacterial DNA gyrase. All the examples investigated are nearly equipotent with the parent 7-piperazinyl analogues. Only endo-7-(3-amino-8-azabicyclo[3.2.1]oct-8-yl)-1-cyclopropyl-6,8-difluoro- 1,4- dihydro-4-oxo-3-quinolinecarboxylic acid displays activity that surpasses that of the piperazine parent.

4-Quinolones↗
PubMed1992

CP-96,345, a non-peptide antagonist of substance P: II. Actions on substance P-induced hypotension and bronchoconstriction, and on depressor reflexes in mammals.

In order to extend the in vivo pharmacological profile of CP-96,345 ((2S,3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)- methyl)-1-azabicyclo[2.2.2]octan-3-amine dihydrochloride), a non-peptide antagonist of substance P, the compound was tested against substance P-induced effects on blood pressure in rabbits and on respiration pressure in guinea-pigs. In addition, CP-96,345, and its inactive (2R,3R)-enantiomer, CP-96,344, were also tested in 2 models involving presumably substance P-mediated reflexes in the rat. The fall in blood pressure evoked by i.v. injections of substance P in the rabbit was inhibited by 0.3 mumol kg-1 CP-96,345 i.v. for at least 30 min, and almost abolished, for at least 2 h, by 3 mumol kg-1. In guinea-pigs, the bronchoconstriction induced by i.v. injections of substance P, but not that in response to histamine or bradykinin, was inhibited by CP-96,345 (0.6 and 6.0 mumol kg-1, i.v.) in a dose-dependent manner and this inhibition lasted for 40 min and 70 min, respectively. CP-96,345 (3-20 mumol kg-1, i.v.) reduced depressor reflexes in response to stimulation of peripheral capsaicin-sensitive neurones in the rat. However, the inhibition was not dose-dependent and was also seen with the inactive enantiomer, CP-96,344. This effect can hardly be attributed to receptor-specific effects of CP-96,345 and may be related to unspecific actions such as those involved in the cardiac depression exhibited by both enantiomers. The present results show that CP-96,345 is a potent antagonist of substance P in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Synthesis and muscarinic M3 pharmacological activities of 1-azabicyclo[2.2.2]octan-3-one oxime derivatives.

A series of 1-azabicyclo[2.2.2]octan-3-one oximes and related 1-azabicyclo-[2.2.2]-octan-3-one hydroxylamines were synthesized and tested for muscarinic M3 activity. All compounds showed at least some muscarinic binding properties, however, only one member of the series demonstrated mucarinic M3 agonistic properties in vitro (contraction of guinea pig ileum) and in vivo (mydriasis, salivation). In addition, this compound partially reversed the cognitive deficit induced by central cholinergic depletion in two procedures testing memory in the rat, namely the delayed matching to position and swim maze tasks of spatial memory in the rat.

Animals↗
PubMed1999

Spiro[1-azabicyclo[5.3.0]decane-6,2'(5'H)-furan]-5',10-dione: an example of kryptoracemic crystallization.

A racemic mixture of the title compound, C12H15NO3, crystallizes in the chiral, monoclinic space group P2(1), with one enantiomerically related pair of molecules per asymmetric unit. This mode of crystallization is extremely rare. The molecules pack to form several close C-H...O interactions. Interestingly, while the conformations of the individual rings in the two molecules are very similar, the overall molecular conformation is different.

Bridged Bicyclo Compounds, Heterocyclic↗
PubMed2000

[Syntheses and applications of optical active bicyclic amino compounds].

This article reviews for our two kinds of projects that lipase-catalyzed asymmetric resolution of bicyclic lactams, 3-oxo-2-azabicyclo[2.2.0]hex-5-enes and 2-azabicyclo[2.2.1]hept-5-en-3-ones, possessing synthetic versatility and the development of a new type of a bicyclic amine-based chiral ligand for a catalytic asymmetric synthesis. Thus, optically active 3-oxo-2-azabicyclo[2.2.0]hex- and 3-oxo-2-azabicyclo[2.2.1]hept-5-enes were obtained conveniently by lipase-catalyzed enantioselective acylation or hydrolysis of racemates, and absolute configurations were determined by chemical correlation, X-ray crystallographic and CD spectral analyses. Furthermore, optically active 2-azanorbornylmethanols, isoquinuclidinylmethanols, 2-azanorbornylmethanethiol, and isoquinuclidinylmethanethiol were prepared from ethyl (1S,3S,4R)-2-[(R)-1-phenylethyl]-2-azabicyclo[2.2.1]hept-5-ene-3- carboxylate easily and their abilities as ligands were examined in the addition of diethylzinc to aldehydes to furnish secondary alcohols up to > 99% ee. Particularly, 2-azanorbornylmethanethiol was the most effective as ligand in the alkylation.

Acylation↗
PubMed2004

Nicotinic acetylcholine receptor-mediated [3H]dopamine release from hippocampus.

The mechanism of nicotinic acetylcholine receptor (nAChR)-induced hippocampal dopamine (DA) release was investigated using rat hippocampal slices. nAChRs involved in hippocampal DA and norepinephrine (NE) release were investigated using prototypical agonists and antagonists and several relatively novel compounds: ABT-594 [(R)-5-(2-azetidinylmethoxy)-2-chloropyridine], (+/-)-UB-165 [(2-chloro-5-pyridyl)-9-azabicyclo [4.2.1]non2-ene], and MG 624 [N,N,N-triethyl-2-[4-(2 phenylethenyl)phenoxy]-ethanaminium iodine]. (+/-)-Epibatidine, (+/-)-UB-165, anatoxin-a, ABT-594, (-)-nicotine, 1,1-dimethyl-4-phenyl-piperazinium iodide, and (-)-cytisine (in decreasing order of potency) evoked [(3)H]DA release in a mecamylamine-sensitive manner. Aside from (+/-)-UB-165, all the agonists displayed full efficacy relative to 100 microM (-)-nicotine in [(3)H]DA release. In contrast, (+/-)-UB-165 was a partial agonist, evoking 58% of 100 microM (-)-nicotine response. Mecamylamine, MG 624, hexamethonium, d-tubocurare, and dihydro-beta-erythroidine (in decreasing order of potency), but not alpha-conotoxin-MII, methyllycaconitine, alpha-conotoxin-ImI, or alpha-bungarotoxin, attenuated 100 microM (-)-nicotine-evoked [(3)H]DA release in a concentration-dependent manner. (+/-)-UB-165, ABT-594, and MG 624 exhibited different pharmacologic profiles in the [(3)H]NE release assay when compared with their effect on [(3)H]DA release. ABT-594 was 4.5-fold more potent, and (+/-)-UB-165 was a full agonist in contrast to its partial agonism in [(3)H]DA release. MG 624 potently and completely blocked NE release evoked by 100 microM (-)-nicotine and 10 microM (+/-)-UB-165, whereas it only partially inhibited (-)-nicotine-evoked [(3)H]DA release. In conclusion, we provide evidence that [(3)H]DA can be evoked from the hippocampus and that the pharmacologic profile for nAChR-evoked hippocampal [(3)H]DA release suggests the involvement of alpha3beta4(*) and at least one other nAChR subtype, thus distinguishing it from that of nAChR-evoked hippocampal [(3)H]NE release.

Animals↗