在树脂上合成兰类表皮和研究它们的结构-活性关系的研究
Arnab Chowdhury1, Nitesh Mani Tripathi1, Rohit Jadav2
1Biomimetic Peptide Engineering Laboratory, Department of Chemistry, Indian Institute of Technology Ropar Rupnagar Punjab-140001 India anupamba@iitrpr.ac.in.
RSC medicinal chemistry
|August 16, 2024
概括
合成像lanreotide (LAN) 这样的类药物的表皮质杂质至关重要. 一个合成的聚物 (P7) 显示了与LAN相似的活性和稳定性,表明作为活性药物成分 (API) 的潜力.
科学领域:
- 药用化学 医学化学
- 类药物开发 药物开发
- 分析化学 分析化学
背景情况:
- 类药物经常含有表皮质杂质,因此需要它们的合成来准确识别和生物评估.
- 了解表皮化对药物有效性和安全性的影响对于药物开发至关重要.
研究的目的:
- 快速合成和表征八种可能的实体静止素合成模拟物 (SSA),lanreotide (LAN).
- 对这些表皮体进行结构-活性关系 (SAR) 研究,并将其与原始药物进行比较.
- 开发一种分析方法,用于分离和分析商业上可用的lanreotide中的表皮质杂质.
主要方法:
- 固相合成 (SPPS),然后在树脂上进行快速二硫化物封闭,以获得高效的聚合物合成 (>90%的产量).
- 开发一种新的分析方法,用于分离和分析合成的表皮质.
- 在体外和在体内进行SAR研究以评估抗增殖活性和血清稳定性.
主要成果:
- 成功合成了八个具有高转换产量的兰类表皮体 (P1-P8).
- 在商业lanreotide API中确定了五种表皮质杂质.
- 与lanreotide相比,大多数合成的epimers表现出较低的抗增殖活性.
- 这种P7体表现出与兰胺API相比较的抗增殖活性和血清稳定性.
- 在体研究支持观察到的SAR趋势.
结论:
- 建立了lanreotide epimers的高效合成和分析分离方法.
- 由于其保留的活性和稳定性,P7体代表了一个有前途的候选人,具有作为活性药物成分 (API) 的潜力.
- 这些发现鼓励进一步探索新的SSA支架和特定epimers的治疗潜力.
相关概念视频
Adrenergic Agonists: Chemistry and Structure-Activity Relationship
2.6K
Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
2.6K
Structure-Activity Relationships and Drug Design
686
Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
686
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
547
Indirect-acting cholinergic agonists are agents that interact with the acetylcholinesterase enzyme in the synaptic cleft, preventing the breakdown of acetylcholine into choline and acetate. Consequently, the concentration of acetylcholine in the synaptic cleft increases. These agonists can be classified into reversible and irreversible inhibitors based on their duration of action.
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
547
The Two-State Receptor Model
1.9K
The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with...
The binding affinity of a drug determines its interaction with...
1.9K
Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
910
Cholinergic agonists or cholinomimetics mimic the action of acetylcholine to stimulate the parasympathetic nervous system. They are categorized into direct-acting and indirect-acting agents. The direct-acting cholinergic drugs induce the parasympathetic response by directly binding to the muscarinic or nicotine receptors. In comparison, the indirect-acting cholinergic drugs prevent acetylcholine hydrolysis, indirectly contributing to the extended parasympathetic response.
The direct-acting...
The direct-acting...
910


