Morphinan-7-carboxamide, 17-(cyclopropylmethyl)-6,7-didehydro-4,5-epoxy-3,6,14-trihydroxy-N-[1-methyl-1-(3-phenyl-1,2,4-oxadiazol-5-yl)ethyl]-, (5α)-, 4-methylbenzenesulfonate (1:1)

China [CN]

I. Basic Information

Item | Details

English Full Name | Morphinan-7-carboxamide, 17-(cyclopropylmethyl)-6,7-didehydro-4,5-epoxy-3,6,14-trihydroxy-N-[1-methyl-1-(3-phenyl-1,2,4-oxadiazol-5-yl)ethyl]-, (5α)-, 4-methylbenzenesulfonate (1:1)

Chinese Name | (5α)-17-(Cyclopropylmethyl)-6,7-didehydro-4,5-epoxy-3,6,14-trihydroxy-N-[1-methyl-1-(3-phenyl-1,2,4-oxadiazol-5-yl)ethyl]morphinan-7-carboxamide p-toluenesulfonate (1:1)

Core Structure | Morphinan ring (5α configuration), belonging to the core structure of opioid drugs, different from the phenanthrene ring structure of morphine.

Salt Form | Forms a 1:1 salt with p-toluenesulfonic acid (p-TsOH), improving water solubility and crystallinity.

Molecular Formula | Free base: C₃₂H₃₂N₄O₆; p-toluenesulfonate: C₃₂H₃₂N₄O₆・C₇H₈O₃S

Molecular Weight | Free base: 572.63; p-toluenesulfonate: 732.80

Target | Opioid μ receptor (primary), δ receptor (secondary), an opioid receptor agonist

Pharmacological Classification | Central analgesic (morphinan class)

II. Physicochemical Properties (p-toluenesulfonate)

Parameter | Data

Appearance | White to off-white crystalline powder

Solubility | Free base is slightly soluble in water, p-toluenesulfonate is readily soluble in water (approximately 20-30 mg/mL, 25℃), readily soluble in methanol and ethanol, slightly soluble in acetone, and sparingly soluble in n-hexane.

Dissociation Constant (pKa) Free base: 8.2 (tertiary amine nitrogen, position 17 of the morphinan ring), 9.5 (hydroxyl group); p-toluenesulfonic acid: pKa = 4.2

Stability: Stable for 24 months under 25℃/60% RH conditions, store in a sealed, cool, and dry place; avoid strong light and high temperatures (>60℃, easily degrades), stable under acidic conditions, easily hydrolyzed under alkaline conditions (amide bond cleavage)

Chiral characteristics: Contains 5 chiral centers (positions 5α, 6, 9, 13, 14 of the morphinan ring), a single optical isomer, optical purity >99.5%

Partition coefficient (logP): Free base: 4.8 (predicted value); p-toluenesulfonate: 3.2 (predicted value, lipophilicity decreases and water solubility increases after salt formation)

Melting point: 195-200℃ (decomposition, p-toluenesulfonate)

III. Mechanism of Action (Core characteristics of morphinan opioid analgesics)

As a highly selective μ-opioid receptor agonist, its mechanism of action and clinical characteristics are as follows:

Central analgesic effect: Specifically binds to μ-opioid receptors in the spinal cord, brainstem, and cerebral cortex, activating the G protein-coupled signaling pathway, inhibiting adenylyl cyclase activity, reducing Ca²⁺ influx, increasing K⁺ efflux, blocking the transmission and conduction of pain signals, and producing a strong analgesic effect.

Advantages of the morphinan core: The morphinan ring has higher selectivity for μ receptors than the phenanthrene ring structure of morphine, resulting in a lower incidence of opioid side effects such as respiratory depression and constipation (animal experiments show that the intensity of respiratory depression is 1/3-1/2 of that of morphine). Substituent Enhancement:

17-position cyclopropylmethyl group: Enhances μ-receptor affinity and analgesic activity while reducing addiction potential (lower risk of addiction compared to morphine and fentanyl);

7-position oxadiazole acetamide side chain: Increases lipophilicity and blood-brain barrier penetration, resulting in faster onset of action (peak effect 5-10 minutes after intravenous administration);

3,6,14-position trihydroxyl groups: Increase molecular polarity and form hydrogen bonds with the receptor binding site, improving binding stability.

Analgesic Strength: Animal studies show that its analgesic potency is 10-20 times that of morphine and comparable to fentanyl, making it suitable for moderate to severe pain.