Coats, Steven J. published the artcileParallel methods for the preparation and SAR exploration of N-ethyl-4-[(8-alkyl-8-aza-bicyclo[3.2.1]oct-3-ylidene)-aryl-methyl]-benzamides, powerful mu and delta opioid agonists, Recommanded Product: Pyrazin-2-ylboronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2004), 14(22), 5493-5498, database is CAplus and MEDLINE.
Libraries of azabicyclooctylidenemethylbenzamides such as I are prepared as μ- and δ-opioid agonists using solid-phase and solution-phase methods; qual. relationships between the structures of azabicyclooctylidenebenzamides and their μ- and δ-opioid agonist activities are discussed. 4-(Methoxycarbonyl)benzyl bromide is converted to di-Me 4-(methoxycarbonyl)benzylphosphonate with tri-Me phosphite; base-mediated olefination of N-(ethoxycarbonyl)tropinone, bromination and base treatment, and cleavage of the Et carbamate followed by replacement with an Fmoc moiety yields the intermediate (carboxyphenylbromomethylene)azabicyclooctanecarboxylate II (R = HO; R1 = Br; R2 = Fmoc). Attachment of II (R = HO; R1 = Br; R2 = Fmoc) to a resin-bound ethylamine yields a solid-phase intermediate which undergoes piperidine-mediated deprotection of the Fmoc group, reductive amination with aldehydes, palladium-catalyzed Suzuki coupling with aryl- or heteroarylboronic acids, and trifluoroacetic acid deprotection to yield azabicyclooctylidenemethylbenzamides. Coupling of II (R = HO; R1 = Br; R2 = Fmoc) to ethylamine and deprotection yields intermediate II (R = EtNH; R1 = Br; R2 = H); microwave-mediated reductive amination of II (R = EtNH; R1 = Br; R2 = H) with aldehydes and sodium triacetoxyborohydride, quenching with water, and microwave-mediated Suzuki coupling in the presence of tetrakis(triphenylphosphine)palladium yields azabicyclooctylidenemethylbenzamides. Azabicyclooctylidenemethylbenzamides substituted with a wide variety of aryl groups at the methylene carbon are effective as μ- and δ-opioid agonist. Small substituents at the nitrogen of the azabicyclooctyl ring in azabicyclooctylidenemethylbenzamides are preferred for good μ- and δ-opioid agonist activity; basic and acidic substituents decrease activity (although the effects of basic groups can be mitigated by appropriate aryl substitution at the methylene carbon). I has Ki values of 6.0 nM for the μ-opioid receptor and 3.8 nM for the δ-opioid receptor and is an effective oral antinociceptive agent at a dose of 150 μmol/kg in a 48° mouse hot plate test.
Bioorganic & Medicinal Chemistry Letters published new progress about 762263-64-9. 762263-64-9 belongs to pyrazines, auxiliary class Pyrazine,Boronic acid and ester,Boronic Acids, name is Pyrazin-2-ylboronic acid, and the molecular formula is C4H5BN2O2, Recommanded Product: Pyrazin-2-ylboronic acid.
Referemce:
https://en.wikipedia.org/wiki/Pyrazine,
Pyrazine | C4H4N2 – PubChem