a-85380 and Neuroblastoma

a-85380 has been researched along with Neuroblastoma* in 2 studies

Other Studies

2 other study(ies) available for a-85380 and Neuroblastoma

Article	Year
Discovery of highly potent and selective α4β2-nicotinic acetylcholine receptor (nAChR) partial agonists containing an isoxazolylpyridine ether scaffold that demonstrate antidepressant-like activity. Part II. Journal of medicinal chemistry, 2012, Nov-26, Volume: 55, Issue:22 In our continued efforts to develop α4β2-nicotinic acetylcholine receptor (nAChR) partial agonists as novel antidepressants having a unique mechanism of action, structure-activity relationship (SAR) exploration of certain isoxazolylpyridine ethers is presented. In particular, modifications to both the azetidine ring present in the starting structure 4 and its metabolically liable hydroxyl side chain substituent have been explored to improve compound druggability. The pharmacological characterization of all new compounds has been carried out using [(3)H]epibatidine binding studies together with functional assays based on (86)Rb(+) ion flux measurements. We found that the deletion of the metabolically liable hydroxyl group or its replacement by a fluoromethyl group not only maintained potency and selectivity but also resulted in compounds showing antidepressant-like properties in the mouse forced swim test. These isoxazolylpyridine ethers appear to represent promising lead candidates in the design of innovative chemical tools containing reporter groups for imaging purposes and of possible therapeutics. Topics: Animals; Antidepressive Agents; Humans; Isoxazoles; Male; Mice; Mice, Inbred BALB C; Motor Activity; Neuroblastoma; Nicotinic Agonists; Protein Binding; Radioligand Assay; Receptors, Nicotinic; Stereoisomerism; Structure-Activity Relationship; Swimming	2012
Identification and initial structure-activity relationships of (R)-5-(2-azetidinylmethoxy)-2-chloropyridine (ABT-594), a potent, orally active, non-opiate analgesic agent acting via neuronal nicotinic acetylcholine receptors. Journal of medicinal chemistry, 1998, Feb-12, Volume: 41, Issue:4 New members of a previously reported series of 3-pyridyl ether compounds are disclosed as novel, potent analgesic agents acting through neuronal nicotinic acetylcholine receptors. Both (R)-2-chloro-5-(2-azetidinylmethoxy)pyridine (ABT-594, 5) and its S-enantiomer (4) show potent analgesic activity in the mouse hot-plate assay following either intraperitoneal (i.p.) or oral (p.o.) administration, as well as activity in the mouse abdominal constriction (writhing) assay, a model of persistent pain. Compared to the S-enantiomer and to the prototypical potent nicotinic analgesic agent (+/-)-epibatidine, 5 shows diminished activity in models of peripheral side effects. Structure-activity studies of analogues related to 4 and 5 suggest that the N-unsubstituted azetidine moiety and the 2-chloro substituent on the pyridine ring are important contributors to potent analgesic activity. Topics: Administration, Oral; Analgesics, Non-Narcotic; Animals; Azetidines; Diastole; Female; Humans; Injections, Intraperitoneal; Kinetics; Mice; Molecular Structure; Muscle Contraction; Neuroblastoma; Neurons; Nicotinic Agonists; Oocytes; Pain; Pain Measurement; Pyridines; Rats; Receptors, Nicotinic; Recombinant Proteins; Stereoisomerism; Structure-Activity Relationship; Tumor Cells, Cultured; Xenopus	1998

Article

Year

Discovery of highly potent and selective α4β2-nicotinic acetylcholine receptor (nAChR) partial agonists containing an isoxazolylpyridine ether scaffold that demonstrate antidepressant-like activity. Part II.

Journal of medicinal chemistry, 2012, Nov-26, Volume: 55, Issue:22

In our continued efforts to develop α4β2-nicotinic acetylcholine receptor (nAChR) partial agonists as novel antidepressants having a unique mechanism of action, structure-activity relationship (SAR) exploration of certain isoxazolylpyridine ethers is presented. In particular, modifications to both the azetidine ring present in the starting structure 4 and its metabolically liable hydroxyl side chain substituent have been explored to improve compound druggability. The pharmacological characterization of all new compounds has been carried out using [(3)H]epibatidine binding studies together with functional assays based on (86)Rb(+) ion flux measurements. We found that the deletion of the metabolically liable hydroxyl group or its replacement by a fluoromethyl group not only maintained potency and selectivity but also resulted in compounds showing antidepressant-like properties in the mouse forced swim test. These isoxazolylpyridine ethers appear to represent promising lead candidates in the design of innovative chemical tools containing reporter groups for imaging purposes and of possible therapeutics.

Topics: Animals; Antidepressive Agents; Humans; Isoxazoles; Male; Mice; Mice, Inbred BALB C; Motor Activity; Neuroblastoma; Nicotinic Agonists; Protein Binding; Radioligand Assay; Receptors, Nicotinic; Stereoisomerism; Structure-Activity Relationship; Swimming

2012

Identification and initial structure-activity relationships of (R)-5-(2-azetidinylmethoxy)-2-chloropyridine (ABT-594), a potent, orally active, non-opiate analgesic agent acting via neuronal nicotinic acetylcholine receptors.

Journal of medicinal chemistry, 1998, Feb-12, Volume: 41, Issue:4

New members of a previously reported series of 3-pyridyl ether compounds are disclosed as novel, potent analgesic agents acting through neuronal nicotinic acetylcholine receptors. Both (R)-2-chloro-5-(2-azetidinylmethoxy)pyridine (ABT-594, 5) and its S-enantiomer (4) show potent analgesic activity in the mouse hot-plate assay following either intraperitoneal (i.p.) or oral (p.o.) administration, as well as activity in the mouse abdominal constriction (writhing) assay, a model of persistent pain. Compared to the S-enantiomer and to the prototypical potent nicotinic analgesic agent (+/-)-epibatidine, 5 shows diminished activity in models of peripheral side effects. Structure-activity studies of analogues related to 4 and 5 suggest that the N-unsubstituted azetidine moiety and the 2-chloro substituent on the pyridine ring are important contributors to potent analgesic activity.

Topics: Administration, Oral; Analgesics, Non-Narcotic; Animals; Azetidines; Diastole; Female; Humans; Injections, Intraperitoneal; Kinetics; Mice; Molecular Structure; Muscle Contraction; Neuroblastoma; Neurons; Nicotinic Agonists; Oocytes; Pain; Pain Measurement; Pyridines; Rats; Receptors, Nicotinic; Recombinant Proteins; Stereoisomerism; Structure-Activity Relationship; Tumor Cells, Cultured; Xenopus

1998