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Synthesis of novel triplet drugs with 1,3,5-trioxazatriquinane skeletons and their pharmacologies. 3: synthesis of novel triplet drugs with the bis(epoxymethano) or bis(dimethylepoxymethano) structure (double-capped triplet)
- Source :
- Bioorganicmedicinal chemistry letters. 22(24)
- Publication Year :
- 2012
-
Abstract
- Novel double-capped triplet drugs, which have one pharmacophore unit and two epoxymethano or dimethylepoxymethano structures (termed cap or diMe-cap structures, respectively) were synthesized. Key intermediate oxazoline 16 derived from acetone enabled the effective synthesis of double-capped triplets. SYK-134 (7a) and SYK-135 (8a) with N-cyclopropylmethyl substituent and cap structures showed selectivities for the κ opioid receptor. On the other hand, the N-Me series exhibited selectivities for the μ opioid receptor. The double-capped triplet drugs with diMe-cap structures preferred the μ receptor independently of their N-substituents. SYK-385 (19b), one of the μ-selective double-capped triplet drugs, showed the highest selectivity for the μ receptor among the reported μ-selective nonpeptide ligands.
- Subjects :
- medicine.drug_class
Stereochemistry
Clinical Biochemistry
Guinea Pigs
Substituent
Receptors, Opioid, mu
Pharmaceutical Science
Oxazoline
Biochemistry
Heterocyclic Compounds, 4 or More Rings
chemistry.chemical_compound
Mice
Structure-Activity Relationship
Opioid receptor
Drug Discovery
medicine
Molecule
Structure–activity relationship
Animals
Molecular Biology
Dose-Response Relationship, Drug
Molecular Structure
Receptors, Opioid, kappa
Organic Chemistry
chemistry
Opioid
Molecular Medicine
Pharmacophore
Selectivity
Methane
medicine.drug
Subjects
Details
- ISSN :
- 14643405
- Volume :
- 22
- Issue :
- 24
- Database :
- OpenAIRE
- Journal :
- Bioorganicmedicinal chemistry letters
- Accession number :
- edsair.doi.dedup.....afda36f1f5d12c78c08c3b393eb61ac1