3-(4-Aminobutyn-1-yl)pyridines: binding at α4β2 nicotinic cholinergic receptors

Dogruer, Deniz S.; Lee, Mase; Dukat, Małgorzata; Damaj, M. Imad; Martin, Billy R.; Glennon, Richard A.

doi:10.1016/j.bmcl.2003.10.033

Cited by 6 publications

(8 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[70] The trend of affinity found in the (6-quinolinyl)butynyl series is different from that reported for their 3-pyridyl analogues: compound 13 a (R 1 = H, R 2 = Me) showed an affinity for rat brain homogenate 4-5 times higher than that of the dimethylamino and trimethylammonium analogues; [71] the agonistic properties of these latter compounds have not been determined.…”

Section: Agonistsmentioning

confidence: 89%

“…[60,71,95] The pharmacophoric patterns of nAChR, both from SAR and computational techniques such as DISCO and Catalyst HipHop, were widely used in the conformer selection and in the alignment of the ligands involved in the development of the nicotinic 3D QSAR models, that is, in the construction of mathematical models aimed at uncovering relationships between chemical properties, the 3D molecular features of the compounds, and biological activity of the set of nicotinic ligands. Such models can be regarded as an empirical picture of the biomacromolecular target and their determination has been accomplished by procedures such as CoMFA, CoMSIA, GRID/GOLPE, or related-field approaches.…”

Section: Allosteric Modulatorsmentioning

confidence: 99%

See 1 more Smart Citation

Central Nicotinic Receptors: Structure, Function, Ligands, and Therapeutic Potential

et al. 2007

View full text Add to dashboard Cite

The growing interest in nicotinic receptors, because of their wide expression in neuronal and non-neuronal tissues and their involvement in several important CNS pathologies, has stimulated the synthesis of a high number of ligands able to modulate their function. These membrane proteins appear to be highly heterogeneous, and still only incomplete information is available on their structure, subunit composition, and stoichiometry. This is due to the lack of selective ligands to study the role of nAChR under physiological or pathological conditions; so far, only compounds showing selectivity between alpha4beta2 and alpha7 receptors have been obtained. The nicotinic receptor ligands have been designed starting from lead compounds from natural sources such as nicotine, cytisine, or epibatidine, and, more recently, through the high-throughput screening of chemical libraries. This review focuses on the structure of the new agonists, antagonists, and allosteric ligands of nicotinic receptors, it highlights the current knowledge on the binding site models as a molecular modeling approach to design new compounds, and it discusses the nAChR modulators which have entered clinical trials.

show abstract

Section: Agonistsmentioning

confidence: 89%

Section: Allosteric Modulatorsmentioning

confidence: 99%

Central Nicotinic Receptors: Structure, Function, Ligands, and Therapeutic Potential

et al. 2007

View full text Add to dashboard Cite

show abstract

“…59 Both compounds are reported to bind with nanomolar affinity to the receptor. 50,60 So it can be suggested that ligands dock into the active site in a way that allows them to interact with different residues according to their own distance between the pharmacophoric points. In this regard, a recently-published study also predicts different binding modes of nicotinic ligands within the active site of the receptor.…”

mentioning

confidence: 99%

Design, synthesis and binding affinity of new nicotinic ligands

Guandalini¹,

Martini²,

Gratteri³

et al. 2006

Arkivoc

View full text Add to dashboard Cite

Nicotinic ligands can be potentially useful as drugs for the management of several important pathologies as well as pharmacological tools to characterize nicotinic receptor subtypes. The design of new nicotinic ligands has been carried out by applying the 3D database search method; thus, the Cambridge Structural Database has been scanned with a query consisting in a pharmacophore substructure with 3D constraints. The nicotinic pharmacophoric features have been obtained from the structure of pyrido[3,4-b]homotropane (PHT), which represents a rigid template. The results of the query suggested the aminoalkylquinoline moiety as simple scaffold, and it was further refined using molecular modeling. Some of the synthesized compounds were found to interact with the central nicotinic receptor on rat cerebral cortex, showing affinity in the nanomolar range and displaying analgesic properties. The possible binding mode of these substances with a homology-built model of the nicotinic receptor has been analyzed by means of induced fit studies.

show abstract

“…injection, its efficacy being similar to that of 9 a and 9 b. 70 The trend of affinity found in the (6‐quinolinyl)butynyl series is different from that reported for their 3‐pyridyl analogues: compound 13 a (R 1 =H, R 2 =Me) showed an affinity for rat brain homogenate 4–5 times higher than that of the dimethylamino and trimethylammonium analogues;71 the agonistic properties of these latter compounds have not been determined.…”

Section: Introductionmentioning

confidence: 99%

“…3D QSAR and QSAR studies on nAChR paralleled the efforts in the development of the pharmacophore models,95, 189, 190, 193, 195–198 supporting the rational design and synthesis of novel nicotinic ligands 60. 71, 95 The pharmacophoric patterns of nAChR, both from SAR and computational techniques such as DISCO and Catalyst HipHop, were widely used in the conformer selection and in the alignment of the ligands involved in the development of the nicotinic 3D QSAR models, that is, in the construction of mathematical models aimed at uncovering relationships between chemical properties, the 3D molecular features of the compounds, and biological activity of the set of nicotinic ligands. Such models can be regarded as an empirical picture of the biomacromolecular target and their determination has been accomplished by procedures such as CoMFA, CoMSIA, GRID/GOLPE, or related‐field approaches.…”

Section: Introductionmentioning

confidence: 99%

Immuno‐intervention and preservation of beta‐cell function in type 1 diabetes

Pozzilli

2007

Diabetes Metabolism Res

View full text Add to dashboard Cite

The growing interest in nicotinic receptors, because of their wide expression in neuronal and non‐neuronal tissues and their involvement in several important CNS pathologies, has stimulated the synthesis of a high number of ligands able to modulate their function. These membrane proteins appear to be highly heterogeneous, and still only incomplete information is available on their structure, subunit composition, and stoichiometry. This is due to the lack of selective ligands to study the role of nAChR under physiological or pathological conditions; so far, only compounds showing selectivity between α4β2 and α7 receptors have been obtained. The nicotinic receptor ligands have been designed starting from lead compounds from natural sources such as nicotine, cytisine, or epibatidine, and, more recently, through the high‐throughput screening of chemical libraries. This review focuses on the structure of the new agonists, antagonists, and allosteric ligands of nicotinic receptors, it highlights the current knowledge on the binding site models as a molecular modeling approach to design new compounds, and it discusses the nAChR modulators which have entered clinical trials.

show abstract

3-(4-Aminobutyn-1-yl)pyridines: binding at α4β2 nicotinic cholinergic receptors

Cited by 6 publications

References 12 publications

Central Nicotinic Receptors: Structure, Function, Ligands, and Therapeutic Potential

Central Nicotinic Receptors: Structure, Function, Ligands, and Therapeutic Potential

Design, synthesis and binding affinity of new nicotinic ligands

Immuno‐intervention and preservation of beta‐cell function in type 1 diabetes

Contact Info

Product

Resources

About