Thomas, James B. published the artcileIdentification of an Opioid κ Receptor Subtype-Selective N-Substituent for (+)-(3R,4R)-Dimethyl-4-(3-hydroxyphenyl)piperidine, Formula: C8H7ClO3, the publication is Journal of Medicinal Chemistry (1998), 41(26), 5188-5197, database is CAplus and MEDLINE.
A three-component library of compounds was prepared in parallel using multiple simultaneous solution-phase synthetic methodol. The compounds were biased toward opioid receptor antagonist activity by incorporating (+)-(3R,4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (a potent, nonselective opioid pure antagonist) as one of the monomers. The other two monomers were N-substituted or unsubstituted Boc-protected amino acids and a range of substituted aryl carboxylic acids and were selected to add chem. diversity. Screening of these compounds in competitive binding experiments with the κ opioid receptor selective ligand [3H]U69,593 led to the discovery of a novel κ opioid receptor selective ligand, RTI-5989-29 (I). Addnl. structure-activity relationship studies suggested that I possesses lipophilic and hydrogen-bonding sites that are important to its opioid receptor potency and selectivity. These sites appear to exist predominantly within the κ receptor since the selectivity arises from a 530-fold loss of affinity of I for the μ receptor and an 18-fold increase in affinity for the κ receptor relative to the μ-selective ligand, (+)-N-[trans-4-phenyl-2-butenyl]-(3R,4R)-dimethyl-4-(3-hydroxyphenyl)piperidine. The degree of selectivity observed in the radioligand binding experiments was not observed in the functional assay. According to its ability to inhibit agonist stimulated binding of [35S]GTPγS at all three opioid receptors, I behaves as a μ/κ opioid receptor pure antagonist with negligible affinity for the δ receptor.
Journal of Medicinal Chemistry published new progress about 33697-81-3. 33697-81-3 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Carboxylic acid,Benzene,Phenol, name is 3-Chloro-4-hydroxyphenylacetic acid, and the molecular formula is C17H37NO3, Formula: C8H7ClO3.
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