188340-69-4

Upstream product

• 7051-34-5 cyclopropylcarbinyl bromide 
• 791566-47-7 N-demethyldihydronepenthone 
• 1207169-33-2 N-cyclopropylmethylnorthevinal 
• 1367597-25-8 N-cyclopropylmethyl-6,14-dihydronorthevinal 
• 100-58-3 phenylmagnesium bromide 
• 182325-11-7 Dihydronepenthone 

Downstream Products

• 1613189-53-9 C₃₄H₄₁NO₄ 

Relevant academic research and scientific papers

BUPRENORPHINE ANALOGS AS OPIOD RECEPTOR MODULATORS

The present invention is directed to Buprenorphine Analog compounds of the Formula 1, Formula II, Formula III, Formula IV, and Formula V, wherein R1, R2, R3a, R3b, R,15a, R15b, X, Q, G, and Y are as defined herein. Compounds of the Invention are useful for treating pain and other conditions modulated by activity of opioid receptors.

Selectively promiscuous opioid ligands: Discovery of high affinity/low efficacy opioid ligands with substantial nociceptin opioid peptide receptor affinity

Emerging clinical and preclinical evidence suggests that a compound displaying high affinity for μ, κ, and δ opioid (MOP, KOP, and DOP) receptors and antagonist activity at each, coupled with moderate affinity and efficacy at nociceptin opioid peptide (NOP) receptors will have utility as a relapse prevention agent for multiple types of drug abuse. Members of the orvinol family of opioid ligands have the desired affinity profile but have typically displayed substantial efficacy at MOP and or KOP receptors. In this study it is shown that a phenyl ring analogue (1d) of buprenorphine displays the desired profile in vitro with high, nonselective affinity for the MOP, KOP, and DOP receptors coupled with moderate affinity for NOP receptors. In vivo, 1d lacked any opioid agonist activity and was an antagonist of both the MOP receptor agonist morphine and the KOP receptor agonist ethylketocyclazocine, confirming the desired opioid receptor profile in vivo.

New nepenthone and thevinone derivatives

The diastereoselective reaction of thevinone (2a) and nepenthone (2c) and their dihydro derivatives (2b and d) with Grignard reagents afforded new N-substituted (20S)- and (20R)-phenyI-6,14-ethenomorphinan derivatives (6a-y). The Grignard reaction of the N-substituted-N-demethyl derivatives 4a-f and 4m-r with methylmagnesium iodide resulted in the (20R)-phenyl tertiary alcohols 5a-f and 5m-r, respectively, but the conversion of 4g-l and that of the N-substituted-dihydrothevinone derivatives with phenylmagnesium bromide afforded the (20S)-phenyl derivatives 5g-l and 5s-y, respectively. The N-cyclopropylmethyl-, N-β-phenylethyl-, and N-propyl derivatives were prepared by the 3-O-demethylation of compounds 5. For the synthesis of the N-allyl-, N-dimethylallyl-, and N-propargyl compounds 2a-d were reacted with the corresponding Grignard reagent, and treatment of the products with cyanogen bromide gave the cyanamides 8a-d. These latter compounds were transformed into 10a,b,d, whose alkylation led to the target derivatives 6d-f, j-l, p-r, and w-y. The biochemical investigation of these substances showed that the affinities to the δ-opioid receptors were high, but the selectivity was low. Tn two cases (6c and 11d) a μ-opioid receptor specificity was observed.