Search results for "Indazole"
showing 10 items of 63 documents
Downregulation of nNOS and synthesis of PGs associated with endotoxin-induced delay in gastric emptying
2002
A single intraperitoneal injection of endotoxin (40 μg/kg) significantly delayed gastric emptying of a solid nutrient meal. Blockade of nitric oxide synthase (NOS) with 30 mg/kg ip N G-nitro-l-arginine methyl ester or 20 mg/kg ip 7-nitroindazole [neuronal NOS (nNOS) inhibitor] significantly delayed gastric emptying in control animals but failed to modify gastric emptying in endotoxin-treated rats. Administration of 2.5, 5, and 10 mg/kg ip N 6-iminoethyl-l-lysine [inducible NOS (iNOS) inhibitor] had no effect in either experimental group. Indomethacin (5 mg/kg sc), NS-398 (cyclooxygenase-2 inhibitor; 10 mg/kg ip), and dexamethasone (10 mg/kg sc) but not quinacrine (20 mg/kg ip) significantl…
Inhibition of nitric oxide synthase influences the activity of striatal neurons in the rat
2002
The activity of single units in the striatum of urethane-anesthetized rats was recorded before and after the systemic administration of 7-nitro-indazole (7-NI; 50 mg/kg intraperitoneally), a selective inhibitor of neuronal nitric oxide (NO) synthase. Two neuronal types were clearly distinguishable electrophysiologically, on the basis of either discharge frequency pattern or features of the individual spike waveform (spike duration, negative phase/total duration ratio, and negative phase/total amplitude ratio). Only sporadically discharging neurons (basal firing rate, <0.1 spikes/s) were influenced by 7-NI, which caused a statistically significant increase in their firing rate. In contrast, …
Involvement of nitric oxide-soluble guanylyl cyclase pathway in the control of maximal dentate gyrus activation in the rat.
2006
Summary Nitric oxide=soluble Guanylyl cyclase (NO=sGC) pathway on the maximal dentate gyrus activation (MDA) was studied in rats. The cerebral NO levels were modified by administrating 7-Nitroindazole (7-NI), a selective inhibitor of neuronal NOS, and L-arginine, a precursor of the synthesis of NO. 1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one (ODQ), a specific inhibitor of the NO-sGC pathway, was administered to study the involvement of cGMP pathway. The epileptic activity of the dentate gyrus was obtained through the repetitive stimulation of the angular bundle; MDA parameters studied were: onset time, MDA duration and post-stimulus afterdischarge (AD) duration. 7-NI caused an increase of M…
Nitric oxide-sensitive guanylyl cyclase inhibits acetylcholine release and excitatory motor transmission in the guinea-pig ileum
1997
Abstract This study examined the mechanism through which nitric oxide inhibits the release of acetylcholine and excitatory motor neurotransmission in the guinea-pig ileum. The selective inhibitor of nitric oxide-sensitive guanylyl cyclase, 1 H -[1,2,4]oxadiazolo[4,3- a ]quinoxalin-1-one (ODQ), concentration-dependently enhanced both basal release (−log EC 50 : 6.8) and electrically (10 Hz) -evoked release (−log EC 50 : 6.0) of [ 3 H]acetylcholine from longitudinal muscle-myenteric plexus preparations preincubated with [ 3 H]choline. The increase by ODQ of basal release appeared to be exocytotic since it was prevented by tetrodotoxin (300 nM) and absence of calcium from the superfusion mediu…
Differential effects of isoliquiritigenin and YC-1 in rat aortic smooth muscle.
1997
We investigated the effects of isoliquiritigenin and YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole) on tension in endothelial-free rat aortic rings precontracted with phenylephrine (3 microM). Both compounds induced a concentration-dependent relaxation (EC50 of YC-1 1.9 microM and of isoliquiritigenin 9.4 microM). The effects developed faster with YC-1 than with isoliquiritigenin, and the effects of YC-1 were potentiated by isoliquiritigenin (10 microM). 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (30 microM) inhibited the effect of YC-1, but not of isoliquiritigenin. These results suggest that the effects of YC-1 are due to stimulation of soluble guanylyl cyclase activity, whereas …
On the reaction of some 5-polyfluoroaryl-1,2,4-oxadiazoles with methylhydrazine: synthesis of fluorinated indazoles
2009
The reaction of 5-polyfluoroaryl-1,2,4-oxadiazoles with methylhydrazine has been studied and the synthesis of fluorinated N-methylindazoles has been realized. Rearrangement reactions showed predominantly formation of N(1)-methylindazole regioisomers. Starting compounds were preliminarily functionalized at the polyfluoroaryl moiety through fluorine displacement with nucleophiles (methanol, methylamine, dimethylamine), allowing the obtainment of target indazoles substituted at the C(6) position.
Reaction between Indazole and Pd-Bound Isocyanides-A Theoretical Mechanistic Study
2018
The mechanism of the addition of indazole (Ind)&mdash
Synthesis, biological evaluation and chemometric analysis of indazole derivatives. 1,2-Disubstituted 5-nitroindazolinones, new prototypes of antichag…
2012
Chagas disease chemotherapy, currently based on only two drugs, nifurtimox and benznidazole, is far from satisfactory and therefore the development of new antichagasic compounds remains an important goal. On the basis of antichagasic properties previously described for some 1,2-disubstituted 5-nitroindazolin-3- ones (21, 33) and in order to initiate the optimization of activity of this kind of compounds, we have prepared a series of related analogs (22-32, 34-38, 58 and 59) and tested in vitro these products against epimastigote forms of Trypanosoma cruzi. 2-Benzyl-1-propyl (22), 2-benzyl-1-isopropyl (23) and 2-benzyl-1-butyl (24) derivatives have shown high trypanocidal activity and low un…
N-(INDAZOLYL)BENZAMIDO DERIVATIVES AS CDK1 INHIBITORS: DESIGN, SYNTHESIS, BIOLOGICAL ACTIVITY, AND MOLECULAR DOCKING STUDIES
2009
A series of N-1H-indazole-1-carboxamides has been synthesized and their effects on both CDK1/cyclin B and the K-562 (human chronic myelogenus leukemia) cell line were evaluated. Using a computational model, we have observed that all the most active compounds 9e, f, i-n exhibited the same binding mode of purvanalol A in the ATP-binding cleft. Although they were able to moderately inhibit the leukemic cell line K-562 and to show inhibitory activity against the Cdc2-Cyclin B kinase in the low micromolar range, they turned out to be non-cytotoxic against HuDe (IZSL) primary cell cultures from human derm. These preliminary results are quite encouraging in view of the low toxicity demonstrated by…
Structure-Activity Relationships and X-ray Structures Describing the Selectivity of Aminopyrazole Inhibitors for c-Jun N-terminal Kinase 3 (JNK3) ove…
2009
c-Jun N-terminal kinase 3alpha1 (JNK3alpha1) is a mitogen-activated protein kinase family member expressed primarily in the brain that phosphorylates protein transcription factors, including c-Jun and activating transcription factor-2 (ATF-2) upon activation by a variety of stress-based stimuli. In this study, we set out to design JNK3-selective inhibitors that had >1000-fold selectivity over p38, another closely related mitogen-activated protein kinase family member. To do this we employed traditional medicinal chemistry principles coupled with structure-based drug design. Inhibitors from the aminopyrazole class, such as SR-3576, were found to be very potent JNK3 inhibitors (IC(50) = 7 nm)…