A simple three-step synthesis of 5-(3-hydroxyphenyl)-2-methyl-2-azabicyclo[3.3.1]nonan-4-ol (3a) was achieved using an osmium tetroxide mediated oxidation of the known intermediate 6. A pyrrolidine-ring variant of 3a (3-(7-(hydroxymethyl)-6-methyl-6-azabicyclo[3.2.1]octan-1-yl)phenol (5)) was isolated when other routes were used. The epimeric hydroxy analogue 4a was synthesized by simple more ..
Target
Sequence: RecName: Full=Delta-type opioid receptor; Short=D-OR-1; Short=DOR-1
Description ..
Comment ..
Gene:OPRD1 Conserved Domain Related Protein 3D Structures
Description ..
Comment ..
Gene:OPRD1 Conserved Domain Related Protein 3D Structures
BioActive Compounds: 6
Description:
Title: Probes for narcotic receptor mediated phenomena. 44. Synthesis of an N-substituted 4-hydroxy-5-(3-hydroxyphenyl)morphan with high affinity and selective ##-antagonist activity.
Abstract: A simple three-step synthesis of 5-(3-hydroxyphenyl)-2-methyl-2-azabicyclo[3.3.1]nonan-4-ol (3a) was achieved using an osmium tetroxide mediated oxidation of the known intermediate 6. A pyrrolidine-ring variant of 3a (3-(7-(hydroxymethyl)-6-methyl-6-azabicyclo[3.2.1]octan-1-yl)phenol (5)) was isolated when other routes were used. The epimeric hydroxy analogue 4a was synthesized by simple inversion of the stereochemistry at C-4. Both N-methyl (3a and 4a) and N-phenethyl (3b and 4b) derivatives were synthesized. The compounds were examined for their opioid receptor affinity and the N-phenethyl analogue 3b was found to have relatively weak affinity for the ##-opioid receptor (K(i)##=##74##nM). However, the N-phenethyl analogue of the C-4 epimer, 4b, had about 15 fold higher affinity than 3b and was selective for the ##-opioid receptor (K(i)##=##4.6##nM). Compound 4b was a moderately potent ##-opioid antagonist (K(e)##=##12##nM), as determined by [(35)S]GTP-##-S assays. Compounds 3b and 4b were energy minimized at the level of B3LYP/6-31G*, and then overlaid onto the 5-phenylmorphan, the (1R,5R,9S)-(-)-enantiomer of 2b (Fig.##1) with the ## or ##-OH group at the C-9 position. The spatial orientation of the hydroxyl moiety in 3b, 4b, 2a, and 2b is proposed to be the structural requirement for high ##-opioid receptor binding affinity and their agonist or antagonist activity. The modest change in spatial position of the hydroxyl moiety, and not the N-substituent, induced the change from potent agonist to an antagonist of moderate potency.
(PMID: 22341895)
Abstract: A simple three-step synthesis of 5-(3-hydroxyphenyl)-2-methyl-2-azabicyclo[3.3.1]nonan-4-ol (3a) was achieved using an osmium tetroxide mediated oxidation of the known intermediate 6. A pyrrolidine-ring variant of 3a (3-(7-(hydroxymethyl)-6-methyl-6-azabicyclo[3.2.1]octan-1-yl)phenol (5)) was isolated when other routes were used. The epimeric hydroxy analogue 4a was synthesized by simple inversion of the stereochemistry at C-4. Both N-methyl (3a and 4a) and N-phenethyl (3b and 4b) derivatives were synthesized. The compounds were examined for their opioid receptor affinity and the N-phenethyl analogue 3b was found to have relatively weak affinity for the ##-opioid receptor (K(i)##=##74##nM). However, the N-phenethyl analogue of the C-4 epimer, 4b, had about 15 fold higher affinity than 3b and was selective for the ##-opioid receptor (K(i)##=##4.6##nM). Compound 4b was a moderately potent ##-opioid antagonist (K(e)##=##12##nM), as determined by [(35)S]GTP-##-S assays. Compounds 3b and 4b were energy minimized at the level of B3LYP/6-31G*, and then overlaid onto the 5-phenylmorphan, the (1R,5R,9S)-(-)-enantiomer of 2b (Fig.##1) with the ## or ##-OH group at the C-9 position. The spatial orientation of the hydroxyl moiety in 3b, 4b, 2a, and 2b is proposed to be the structural requirement for high ##-opioid receptor binding affinity and their agonist or antagonist activity. The modest change in spatial position of the hydroxyl moiety, and not the N-substituent, induced the change from potent agonist to an antagonist of moderate potency.
(PMID: 22341895)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.
Categorized Comment
ChEMBL Assay Type: Binding
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Target ID: 136
ChEMBL target type: Target is a single protein chain
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Target ID: 136
ChEMBL target type: Target is a single protein chain
Result Definitions
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| TID | Name | Description | Histogram | Type | Unit | |
|---|---|---|---|---|---|---|
| Outcome | The BioAssay activity outcome | Outcome | ||||
| 1 | Ki* | Ki PubChem standard value |  | Float | μM | |
| 2 | BEI | Binding Efficiency Index(nM) | | Float | ||
| 3 | SEI | Surface Efficiency Index(nM) | | Float | ||
| 4 | Ki activity comment | Ki activity comment | String | |||
| 5 | Ki standard flag | Ki standard flag | | Integer | ||
| 6 | Ki qualifier | Ki qualifier | String | |||
| 7 | Ki published value | Ki published value | | Float | nM | |
| 8 | Ki standard value | Ki standard value | | Float | nM | |
| 9 | Ki binding domains | Ki binding domains | String |
* Activity Concentration.
Data Table (Concise)
Classification
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