Zenazocine mesylate is a synthetic compound primarily classified as a non-selective opioid receptor agonist. It has garnered attention in pharmacological research due to its unique properties and potential applications in pain management and other therapeutic areas. The compound is derived from the modification of existing opioid structures, aiming to enhance efficacy while minimizing adverse effects associated with traditional opioids. Buy Zenazocine (WIN-42964) Cas 74559-85-6

Zenazocine mesylate is synthesized in laboratory settings, utilizing various chemical precursors and reagents. The compound’s development is rooted in the need for effective analgesics that can overcome the limitations of conventional opioids, such as tolerance and addiction. Buy Zenazocine (WIN-42964) Cas 74559-85-6, Buy Zenazocine (WIN-42964) Cas 74559-85-6, Buy Zenazocine (WIN-42964) Cas 74559-85-6, Buy Zenazocine (WIN-42964) Cas 74559-85-6, Buy Zenazocine (WIN-42964) Cas 74559-85-6, Buy Zenazocine (WIN-42964) Cas 74559-85-6, Buy Zenazocine (WIN-42964) Cas 74559-85-6, Buy Zenazocine (WIN-42964) Cas 74559-85-6, Buy Zenazocine (WIN-42964) Cas 74559-85-6, Buy Zenazocine (WIN-42964) Cas 74559-85-6, Buy Zenazocine (WIN-42964) Cas 74559-85-6

Zenazocine mesylate is classified under the category of opioid analgesics. It interacts with multiple opioid receptors, including the mu, delta, and kappa receptors, which are known to mediate pain relief and other physiological responses.

Methods

The synthesis of Zenazocine mesylate involves several key steps, typically starting from a precursor compound that undergoes various chemical transformations. The general synthetic route includes:

1. Formation of the Core Structure: The initial step involves the construction of the central phenanthrene or morphinan skeleton, which serves as the backbone for the compound.
2. Modification with Functional Groups: Subsequent reactions introduce specific functional groups that enhance receptor binding affinity and selectivity.
3. Mesylation: The final step involves the introduction of the mesylate group, which is crucial for improving solubility and pharmacokinetic properties.

Technical Details

The synthesis may utilize techniques such as:

• Refluxing: To facilitate reactions at elevated temperatures.
• Chromatography: For purification of intermediates and final products.
• Spectroscopic Methods: Including Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS) for structural confirmation.

Structure

The molecular structure of Zenazocine mesylate can be represented by its chemical formula, which includes carbon, hydrogen, nitrogen, oxygen, and sulfur atoms. The specific arrangement of these atoms defines its pharmacological properties.

Data

• Molecular Formula: CxHyNzOwSz (exact values depend on specific substitutions).
• Molecular Weight: Approximately 400-500 g/mol (varies based on structure).
• 3D Structure: Can be visualized using molecular modeling software to understand its interaction with opioid receptors.

Reactions

Zenazocine mesylate can participate in various chemical reactions typical of opioid compounds:

• Hydrolysis: In aqueous environments, leading to the breakdown of the mesylate group.
• Oxidation/Reduction: Potential modifications that alter its activity profile.
• Substitution Reactions: Where functional groups can be exchanged or modified to enhance efficacy.

Technical Details

The reactivity of Zenazocine mesylate is influenced by its functional groups and steric hindrance within its structure. These factors play a significant role in determining its stability and interaction with biological systems.

Process

Zenazocine mesylate exerts its effects primarily through agonistic activity at opioid receptors. The mechanism involves:

1. Receptor Binding: Zenazocine mesylate binds to mu-opioid receptors in the central nervous system.
2. Signal Transduction: This binding activates intracellular signaling pathways, primarily involving G-proteins.
3. Physiological Response: The activation leads to decreased neurotransmitter release (e.g., substance P), resulting in analgesia.

Data

Studies have shown that Zenazocine mesylate has a binding affinity comparable to other potent opioids but with a distinct profile that may reduce side effects such as respiratory depression.

Physical Properties

• Appearance: Typically exists as a white crystalline powder.
• Solubility: Soluble in organic solvents like ethanol; limited solubility in water due to hydrophobic characteristics.
• Melting Point: Specific melting point data may vary but often falls within a range typical for similar compounds.

Chemical Properties

• Stability: Generally stable under standard laboratory conditions but sensitive to light and moisture.
• pH Sensitivity: May exhibit changes in solubility or stability based on pH levels.

Scientific Uses

Zenazocine mesylate is primarily studied for its potential applications in:

• Pain Management: As an analgesic agent for acute and chronic pain conditions.
• Research Models: Utilized in pharmacological studies to better understand opioid receptor interactions and develop safer analgesics.
• Therapeutic Development: Investigated as a candidate for formulations aimed at reducing opioid dependence while maintaining effective pain relief.

Discovery and Development Within the Benzomorphan Analogue Series

Zenazocine Mesylate originated from systematic structural modifications of the benzomorphan scaffold, a class of compounds first investigated in the 1960s for their potent analgesic properties with reduced addiction potential compared to traditional morphinan opioids. The benzomorphan nucleus is characterized by a partially reduced phenanthrene structure with a dimethylaminoethyl side chain, creating a distinctive tricyclic framework that enables diverse pharmacological activities depending on specific substituents. Zenazocine was synthesized as part of a molecular optimization program targeting compounds with mixed agonist-antagonist activity at opioid receptors [1] [8].

The molecular structure of Zenazocine (chemical name: 1-[(1S,9R)-4-hydroxy-1,10,13-trimethyl-10-azatricyclo[7.3.1.02,7]trideca-2,4,6-trien-13-yl]-6-methyl-3-heptanone) features critical benzomorphan elements including the characteristic aromatic ring and piperidine nitrogen, while incorporating a unique 6-methyl-3-heptanone side chain that distinguished it from earlier analogues like pentazocine and cyclazocine. The mesylate salt (methanesulfonate salt) was developed to improve solubility and crystallinity for pharmaceutical processing, with the salt form having the chemical formula C₂₃H₃₅NO₂·CH₄O₃S and molecular weight of 453.635 g/mol [3] [8].

Table 1: Chemical Profile of Zenazocine Mesylate

The development pathway reflected a deliberate shift from pure μ-opioid receptor agonists toward compounds with mixed receptor activities. Early pharmacological screening demonstrated that Zenazocine Mesylate exhibited the targeted mixed agonist-antagonist profile, producing antinociceptive effects in animal models while potentially reducing abuse liability compared to full μ-agonists. This promising preclinical profile supported advancement to human clinical trials during the late 1970s and early 1980s, where it underwent Phase I safety evaluation and Phase II efficacy assessment before development termination [1] [3].

Structural Classification as a Mixed Opioid Agonist-Antagonist

Zenazocine Mesylate belongs to the benzomorphan subclass of opioids characterized by a partially reduced phenanthrene core structure with a dimethylaminoethyl side chain. This specific structural framework enables distinctive interactions with opioid receptor subtypes that differ from those of morphinan-derived opioids or fully synthetic piperidine derivatives. The compound exists as a racemic mixture containing both enantiomers, with the (2R,6S,11S) configuration identified as the biologically active form responsible for opioid receptor interactions [3] [8].

Pharmacological characterization revealed that Zenazocine functions as a partial agonist at the μ-opioid receptor (MOR) with low intrinsic activity, producing limited analgesic efficacy through this pathway while simultaneously acting as a partial agonist at the δ-opioid receptor (DOR) with comparatively higher intrinsic activity. This dual activity profile positioned Zenazocine Mesylate pharmacologically as a mixed agonist-antagonist, with predominant antagonistic behavior at the MOR and agonistic activity at the DOR. The differential intrinsic activity at these receptors distinguished it from earlier benzomorphans and contributed to its unique pharmacological effects [1].

Table 2: Comparative Receptor Binding Profile of Benzomorphan Opioids

The structural basis for this mixed activity profile resides in specific molecular features: the 4-hydroxy aromatic ring provides essential hydrogen bonding capacity for receptor interaction, while the 6-methyl-3-heptanone side chain creates steric and electronic properties that modulate receptor activation efficacy. Molecular modeling suggests that the extended hydrophobic side chain impedes optimal positioning within the MOR activation pocket while allowing productive engagement with DOR conformations associated with partial agonism. This differential engagement underlies the compound’s ability to produce antinociception primarily through DOR-mediated pathways while antagonizing full MOR agonists [1] [8].

Termination of Clinical Development: Scientific and Methodological Factors

Zenazocine Mesylate reached Phase II clinical trials for pain management indications before development was permanently halted. Analysis of available evidence indicates termination resulted from multifactorial challenges spanning pharmacological limitations, clinical trial methodology constraints, and evolving developmental priorities rather than isolated safety concerns [1] [3].

The primary scientific factor contributing to discontinuation involved inadequate therapeutic efficacy relative to established analgesics. Despite promising antinociceptive effects in animal models, Zenazocine Mesylate demonstrated insufficient analgesic efficacy in human trials across multiple pain models. This efficacy deficit likely stemmed from its suboptimal intrinsic activity profile at opioid receptors—specifically, the low intrinsic activity at the μ-opioid receptor combined with partial δ-agonism failed to produce consistently robust analgesia comparable to full MOR agonists. Additionally, its physicochemical properties, particularly the molecular weight (453.635 g/mol) and lipophilicity (LogP ~4.71), potentially limited central nervous system penetration across the blood-brain barrier, restricting access to central opioid receptors critical for analgesic efficacy [2] [9].

Methodological factors in clinical development further contributed to discontinuation. Phase II trial designs contemporary to Zenazocine’s development often employed conventional analgesic assessments insufficiently sensitive to detect partial agonist efficacy. Additionally, the compound’s development coincided with increasing recognition that drug tissue exposure and selectivity critically influence clinical outcomes—factors not adequately addressed in early-phase trials. The emerging Structure-Tissue Exposure/Selectivity-Activity Relationship (STAR) framework suggests Zenazocine may have been classified as a Class II agent (high specificity but low tissue exposure/selectivity) or Class IV agent (low specificity and low tissue exposure), both associated with high failure risk due to either insufficient efficacy or unacceptable toxicity profiles at therapeutic doses [2] [7].

The broader context of developmental attrition further contextualizes Zenazocine’s discontinuation. Contemporary analyses indicate approximately 90% of drug candidates entering clinical development ultimately fail, with 40-50% failing due to inadequate efficacy and 30% due to safety concerns. Opioid development faces particular challenges, with Phase II failure rates exceeding 70% and Phase III failure approaching 50%, significantly higher than non-CNS therapeutic areas. Zenazocine Mesylate’s termination exemplifies these industry-wide challenges in developing centrally-acting agents with complex pharmacological profiles [4] [7].

Table 3: Clinical Development Failure Factors Relevant to Zenazocine Mesylate