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At least 1,333 records · Page 74Linked to original sources
PubMed1990

Synthesis and bioactivity of propranolol analogues with a rigid skeleton. I.

The synthesis of two kinds of propranolol analogues, A and B, with a rigid skeleton was investigated. The compounds were designed to help identify the conformation involved in beta-adrenergic receptor-propranolol interaction. The key intermediate, 2-hydroxy.2,3-dihydronaphtho[1,8-bc]pyran (5), was obtained starting from acenaphthenone (1). On sequential dehydration, hydroboration, and oxidation, 5 gave 2,3-dihydronaphtho[1,8-bc]pyran-3-one (8), which was converted to compound A. Compound 5 was also derived to 2-formyl-2,3-dihydronaphtho[1,8-bc]pyran (13) via the 2-vinyl compound (12). Condensation of nitromethane with 13 followed by reduction and alkylation produced the desired compound B. The beta-blocking activities of A and B were examined.

Adrenergic beta-Antagonists↗
PubMed1990

Possible involvement of lymphocyte activating factor (LAF) as an endogenous pyrogen in fever induced by the cell wall skeleton of Nocardia rubra (N-CWS).

We investigated whether interleukin-1 (IL-1) acts as an endogenous pyrogen (EP) on the fever caused by the cell wall skeleton of Nocardia rubra (N-CWS) in guinea pigs. IL-1 activity was expressed as potency of lymphocyte activating factor (LAF). When guinea pig peritoneal macrophages were pulse-stimulated with N-CWS (1-100 micrograms/ml), dose-dependent LAF activity was detected in the supernatants after culture for 4 h. Gel filtration of the culture supernatants on Sephadex G-200 showed that the fractions with LAF activity were not the same as those with cytotoxic activity for L-929 cells, which was measured as an index of tumor necrosis factor (TNF) in parallel with LAF activity. Pyretic activity was detected both in the fractions with LAF activity and in those with cytotoxic activity for L-929 cells. Furthermore, when these macrophages were pulse-stimulated again, this time with the supernatant obtained from macrophages previously pulse-stimulated with N-CWS, LAF and cytotoxic activity for L-929 cells continued to be released from the macrophages. We suggest that IL-1 might be a possible EP in the process of fever elicited by N-CWS, and that such an EP stimulates the macrophages to release further IL-1 or TNF. The resultant long-lasting fever would thus be caused by the continuous release of an EP.

Animals↗
PubMed1993

New fluorinated dopamine D2 ligands with benzofuran skeleton. The synthesis and in vitro evaluation.

New fluorinated ligands with N-[(1-ethyl-2-pyrrolidinyl)methyl]-2,3-dihydrobenzofuran-7-carboxamide skeleton, which are useful as a prototype to develop 18F labelled in vivo radiotracer for positron emission tomography (PET), were synthesized, and their binding affinities for the dopamine D2 receptors were investigated. Fluorine atom was introduced at C-4 of the pyrrolidine ring (10) or at ethyl substituent at C-5 of the dihydrobenzofuran moiety (20). The in vitro IC50 values of these ligands for the dopamine D2 receptors which were determined by their ability to inhibit the binding of [3H]spiperone binding in rat striatal membrane were 17 and 36 nM, respectively. Thus, the fluorinated compounds 10 and 20 may be possible candidates for further in vivo investigation.

Animals↗
PubMed1997

Synthesis of novel succinamide derivatives having a 5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one skeleton as potent and selective M2 muscarinic receptor antagonists. II.

A series of succinamide derivatives containing the 5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one skeleton (6a-z) was prepared and evaluated for binding affinity to muscarinic receptors in vitro and for antagonism of bradycardia and salivation in vivo in comparison with AF-DX 116 (1a). Structure-activity relationships (SAR) studies in vitro indicated that the 4-(4-alkyl-1-piperazinyl)benzylamino moiety plays a crucial role in enhancing the affinity for M2 muscarinic receptors. Compound 6y, containing a 4-(4-isopropyl-1-piperazinyl)benzylmethylamino moiety, exhibited the highest affinity for M2 muscarinic receptors (pKi = 9.2), being 200 times as potent as 1a, and compound 6u, containing a 4-(4-ethyl-1-piperazinyl)benzylethylamino moiety, showed the highest selectivity for M2 over M3 muscarinic receptors (M3/M2 ratio = 320). Both 6y and 6u antagonized the oxotremorine-induced bradycardia in rats after intravenous or oral administration. Oral evaluation in conscious dogs showed that the efficacy for increasing the heart rate was at least 3-fold greater than that of 1a.

Amides↗
PubMed1997

Antitumor agents. 169 Dysoxylum cumingianum. V. Cumingianosides P and Q, new cytotoxic triterpene glucosides with an apotirucallane-type skeleton from Dysoxylum cumingianum.

Detailed chemical studies on the cytotoxic fraction from the leaves of Dysoxylum cumingianum have resulted in the isolation of two new triterpene glucosides, cumingianosides P (18) and Q (19), with an apotirucallane-type skeleton. The structures of 18 and 19 were determined by spectral examinations, and by conversion of cumingianosides C (3) and A (1) into 18 and 19, respectively. The cytotoxicities of cumingianosides P and Q against over 50 human cancer cell lines were evaluated. Cumingianoside P exhibited significant (EC50 < 4 microM) cytotoxicity against 37 human cancer cell lines. Among them, the UO-31 (renal cancer) cell line was the most sensitive to this compound (EC50 0.267 microM). In contrast, cumingianoside Q showed selective cytotoxicity against NCI-H522 (non-small cell lung cancer) cells with an EC50 value of 1.67 microM, and exhibited no cytotoxicity (EC50 > 10 microM) against most of the remaining cancer cell lines.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Antitumor agents. 168. Dysoxylum cumingianum. IV. The structures of cumingianosides G-O, new triterpene glucosides with a 14,18-cycloapotirucallane-type skeleton from Dysoxylum cumingianum, and their cytotoxicity against human cancer cell lines.

Nine new triterpene glucosides, named cumingianosides G-O (4-7, 9, 12-15), containing a 14,18-cycloapotirucallane-type skeleton were isolated from a cytotoxic fraction of the leaves of Dysoxylum cumingianum. The structures of the new compounds were established on the basis of chemical and spectral examinations. Evaluation of the cytotoxic activity of cumingianosides G-O showed that cumingianoside M exhibited significant (< 4 microM) cytotoxicity, especially against leukemia and melanoma cell lines.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Synthesis of novel succinamide derivatives having the 5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one skeleton as potent and selective M2 muscarinic receptor antagonists. I.

A series of 5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one derivatives containing the succinamide skeleton has been synthesized and evaluated for M1, M2 and M3 muscarinic receptor binding affinities (in vitro) and M2 and M3 muscarinic receptor antagonistic activities (in vivo). Some of them showed higher and more selective binding affinities for M(2) muscarinic receptors than that of AF-DX 116. Among them, 11-[3-[N-[2-(N-benzyl-N- methylamino)ethyl]-N-ethylcarbamoyl]propionyl]-5,11-dihydro-6H-pyr ido [2,3-b][1,4]benzodiazepin-6-one (68) was found to be the most potent and selective M2 muscarinic receptor antagonist in vitro. This compound also strongly inhibited the oxotremorine-induced bradycardia after intravenous administration and showed 130-fold selectivity for M2 muscarinic receptors over M3 muscarinic receptors in vivo.

Amides↗
PubMed1999

A novel synthesis of benzo[c]phenanthridine skeleton and biological evaluation of isoquinoline derivatives.

Benzo[c]phenanthridine skeleton was synthesized from easily available starting N-methyl-o-toluamide 2 and o-methylbenzonitrile 5 in 7 steps. Radical cyclization of styrene 10 afforded 6,11-dimethyl-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-5-one 13. Most 3-arylisoquinolines have displayed strong activities against human tumor cell lines. Especially, indenoisoquinolinone 13 exhibited excellent cytotoxicity (IC50 = 0.002 microgram/ml; HCT 15).

Antineoplastic Agents↗
PubMed2004

Synthesis and evaluation of 1-arylsulfonyl-3-piperazinone derivatives as factor Xa inhibitors IV. A series of new derivatives containing a spiro[5H-oxazolo[3,2-a]pyrazine-2(3H),4'-piperidin]-5-one skeleton.

In the course of development of factor Xa (FXa) inhibitor in an investigation involving the synthesis of 1-arylsulfonyl-3-piperazinone derivatives, we found new compounds containing a unique spiro skeleton. Among such compounds, (-)-7-[(6-chloro-2-naphthalenyl)sulfonyl]tetrahydro-8a-(methoxymethyl)-1'-(4-pyridinyl)-spiro[5H-oxazolo[3,2-a]pyrazine-2(3H),4'-piperidin]-5-one (28, M55529) had activity more favorable than those of previously reported compounds. The inhibitory activity of M55529 for FXa is IC(50)=2 nM, with high selectivity for FXa over thrombin and trypsin.

Crystallography, X-Ray↗
PubMed2006

Fungal citridone D having a novel phenylfuropyridine skeleton.

Citridone D was isolated from the culture broth of Penicillium sp. FKI-1938 by solvent extraction, silica gel column chromatography and HPLC. The structure of citridone D was elucidated by spectroscopic analysis including NMR analysis. Citridone D was found to have a novel phenylfuropyridine skeleton different from those of other citridones. Citridone D potentiated miconazole activity against Candida albicans.

Heterocyclic Compounds, 4 or More Rings↗
PubMed2006

Syntheses of biologically active natural products and leading compounds for new pharmaceuticals employing effective construction of a polycyclic skeleton.

Cascade reactions are useful methods for the construction of polycyclic skeletons, which are important cores for biological activities. A variety of cascade reactions carried out under multiple reaction conditions, such as pericyclic, polar, radical, and transition metal-catalyzed reaction conditions, have been investigated. Culmorin, pentalenene, pentalenic acid, deoxypentalenic acid, longiborneol, cedrandiol, 8,14-cedranoxide, atisirene, atisine, and estrane-type steroids were synthesized via the intramolecular double Michael reaction. Aza double Michael reaction was applied to the syntheses of tylophorine, epilupinine, tacamonine, and paroxetine. Furthermore, sequential Michael and aldol reactions were performed in both intramolecular and intermolecular manners, leading to the formation of polycyclic compounds fused to a four-membered ring. Synthesis of paesslerin A utilizing a multicomponent cascade reaction revealed an error in the proposed structure. Unique cascade reactions carried out under radical and transition metal-catalyzed reaction conditions were also investigated. With the combination of several cascade reactions, serofendic acids and methyl 7beta-hydroxykaurenoate, both of which have neuroprotective activity, were synthesized in a selective manner.

Alkaloids↗
PubMed2000

[Preparation of novel specific aminopeptidase inhibitors with a cyclic imide skeleton].

The studies on both structure-activity relationship study and identification of the target enzyme of novel nonpeptide aminopeptidase inhibitors with cyclic imide skeleton are reviewed. Some N-phenylphthalimide or N-phenylhomophthalimide derivative showed potent protease inhibitory activity in an assay system using human acute lymphoblastic leukemia cells, Molt-4, with alanin-4-methylcoumaryl-7-amide (ala-AMC) as a substrate. Especially, 2-(2,6-diethylphenyl)-1,2,3,4-tetrahydroisoquinoline-1,3-dione (PIQ-22) (3) was found to be the most potent inhibitor and further it showed potent tumor-cell invasion inhibitory activity that is more effective than potent peptide aminopeptidase inhibitors such as bestatin (1) or actinonin (2). For the further investigation of this novel protease inhibitory activity, we have carried out the structural development of PIQ-22 (3) and it is assumed that tautomerism of imidobenzoylketone in cyclic imide structure may be related to the inhibitory activity. The requirement for the activity of electron donating groups such as NH2 or OH to the condensed phenyl ring in phthalimide inhibitors also supports this possibility. The target aminopeptidase of PIQ-22 was identified as puromycin-sensitive aminopeptidase (PSA), by N-terminal amino acid sequencing, and by comparison with chromatographic behavior and substrate-selectivity, and so on. Lineweaver-Burk plot showed that PSA is inhibited by PIQ-22 (3) in a noncompetitive manner while puromycin (83) and bestatin (1) inhibit PSA competitively.

Aminopeptidases↗
PubMed2004

Intraoperative 3D imaging of the facial skeleton using the SIREMOBIL Iso-C3D.

OBJECTIVES: With respect to high-contrast structures, cone beam computed tomography (CBCT) offers an alternative imaging modality to computed tomography (CT), requiring less radiation exposure. The C-arm system SIREMOBIL Iso-C3D for three-dimensional (3D) reconstruction has made this modality available for intraoperative use. This paper presents the first intraoperative images of the facial skeleton using the SIREMOBIL Iso-C3D. METHODS: Cases of a zygomaticomaxillary complex fracture, a mandibular angle fracture and a bimaxillary repositioning osteotomy are described to demonstrate the application possibilities of this system in maxillofacial surgery. RESULTS: In addition to the uncomplicated handling of the SIREMOBIL Iso-C3D, generally important was the low level of metal artefacts in its primary and secondary reconstructions, even in close proximity to the material. However, it has to be kept in mind that while soft tissues are visualized using CBCT, information about soft tissue quality cannot be obtained. CONCLUSION: The SIREMOBIL Iso-C3D generates intraoperative data sets suitable for the visualization of the facial bones after open reduction of fractures.

Adolescent↗
PubMed2005

Biosynthetic origin of the carbon skeleton and nitrogen atom of pamamycin-607, a nitrogen-containing polyketide.

The biosynthesis of pamamycin-607 (PM-607), a sixteen-membered macrodiolide compound, was studied with 13C- and 15N-labeled precursor units in Streptomyces alboniger. Feeding experiments with 13C-labeled acetate or propionate indicate that the carbon skeleton of PM-607 was derived from six acetate, four propionate and three succinate units. MS analyses of 15N-labeled PM-607 suggest that the nitrogen atom in PM-607 was derived from the alpha-amino group of an amino acid.

Carbon Isotopes↗
PubMed2002

Cartilaginous lesions of the skeleton.

Cartilaginous lesions of the skeleton include those due to genetic diseases (skeletal dysplasias), reparative and hamartomatous processes, and benign and malignant tumors. We review the lesions most commonly encountered by the surgical pathologist, their differential diagnoses, and recently discovered features of these lesions.

Adult↗
PubMed2004

"The visible skeleton series": the art of Laura Ferguson.

Laura Ferguson's The Visible Skeleton Series constitutes an artistic self-representation of scoliosis. Ferguson employs high-tech medical imaging and innovative graphical techniques to suggest a novel view of her skeletal "deformity." This section presents introductions to the series by a historian of medicine and by the artist herself, and offers personal and professional reflections on the work from an orthopedic surgeon, a social worker with lived experience of cleft lip, and a retired pediatric forensic pathologist.

Adaptation, Psychological↗