Parallel 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

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 22, 2004, Pages 5493-5498

  Coats, Steven J ^a   Schulz, Mark J ^a   Carson, John R ^a   Codd, Ellen E ^a   Hlasta, Dennis J ^a   Pitis, Philip M ^a   Stone Jr , Dennis J ^a   Zhang, Sui Po ^a   Colburn, Ray W ^a   Dax, Scott L ^a  

^a LLC Welsh McKean Roads PO B ^*  (United States)

Author keywords

Antinociception; Delta; Mu; Opioid; Parallel

Indexed keywords

BENZAMIDE DERIVATIVE; DELTA OPIATE RECEPTOR AGONIST; MU OPIATE RECEPTOR AGONIST;

ANIMAL EXPERIMENT; ANTINOCICEPTION; ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; HOT PLATE TEST; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION;

ANALGESICS; ANIMALS; BENZAMIDES; MICE; MOLECULAR STRUCTURE; PAIN MEASUREMENT; RECEPTORS, OPIOID, DELTA; RECEPTORS, OPIOID, MU; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 5144228817     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2004.09.004     Document Type: Article

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23. Representative procedure: To a solution of 4-[(8-aza-bicyclo[3.2.1]oct-3- ylidene)-bromo-methyl]-N-ethyl-benzamide, 12 (10 mg, 0.029 mmol) and the appropriate aldehyde (0.087 mmol) in dichloroethane (0.5 mL) was added sodium triacetoxyborohydride (12 mg, 0.058 mmol) in dimethylformamide (100 μL) and acetic acid (5 μL). The reaction mixture was irradiated (μw) at 120°C for 6 min. After quenching with water, the mixture was concentrated in vacuo. To the resulting residue in N-methyl pyrrolidinone (0.3 mL) was added potassium carbonate (12 mg, 0.087 mmol) in water (100 μL), the appropriate boronic acid (0.087 mmol), and tetrakis(triphenylphosphine)palladium (1.5 mg, 0.001 mmol) in N-methyl pyrrolidinone (100 μL). The reaction mixture was irradiated (μw) at 180°C for 10 min. After quenching with water, the mixture was absorbed onto diatomaceous earth and eluted with 5% methanol/ethyl acetate. The eluate was concentrated to a residue and purified by reversed-phase chromatography to furnish the product as a trifluoroacetate salt
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