Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Ghal Kalan, Ferozpur G.T. Road, MOGA, 142001, Punjab, India; Department of Pharmaceutical Chemistry, Laureate Institute of Pharmacy, Kathog, Jawalaji, Kangra, 177101, Himachal Pradesh, India.
Department of Pharmaceutical Chemistry, Laureate Institute of Pharmacy, Kathog, Jawalaji, Kangra, 177101, Himachal Pradesh, India.
Eur J Med Chem. 2022 Apr 15;234:114269. doi: 10.1016/j.ejmech.2022.114269. Epub 2022 Mar 14.
Gamma-Aminobutyric Acid (GABA) inhibitory neurotransmitter departs an energetic role in brain signalling system. Levels of GABA in the brain influence human behaviour, diminishes in the degree of GABA can cause seizures, depression, Parkinson's. To put it plainly, it plays a basic part in the significant issues of mind. It is exceptionally important to cure the issues linked to GABA. Writing overview proposed that nipecotic acid is an intense GABA reuptake inhibitor. This scaffold is likewise present in one of the promoted anticonvulsant drugs 'Tiagabine'. Tiagabine is only drug in the market which works through this mechanism however the medication is regulated with one more prescription for the synergistic impact. Nipecotic acid has several disadvantages such as it can't cross the blood-brain barrier because of its hydrophilic and zwitterionic nature. To avoid this problem nipecotic acid scaffold hybrids with the different aromatic groups can enhance the physical (lipophilicity) as well as biological properties of the resultant compound. So, there is a dire requirement for compounds that work through this mechanism. Several medicinal chemists and researchers are already working in this field and developed outstanding newer molecules. This review article compiles these developed new hybrids along with design strategies, structure-activity relationship, and biological activity as well as in silico studies. This review also demonstrates the synthesis of nipecotic acid and the core mechanism through which nipecotic acid acts as a GABA reuptake inhibitor.
γ-氨基丁酸（GABA）是一种抑制性神经递质，在大脑信号系统中起着重要的能量作用。大脑中的 GABA 水平影响着人类的行为，GABA 水平的降低会导致癫痫、抑郁、帕金森等疾病。简单来说，它在大脑的重要问题中起着基本作用。因此，治疗与 GABA 相关的问题非常重要。研究表明，烟酰胺是一种强烈的 GABA 重摄取抑制剂。这个支架也存在于已推广的抗惊厥药物之一“噻加宾”中。噻加宾是市场上唯一一种通过这种机制起作用的药物，但由于协同作用的影响，该药受到另一种处方的管制。烟酰胺有几个缺点，例如由于其亲水性和两性离子性质，它不能穿过血脑屏障。为了解决这个问题，烟酰胺支架可以与不同的芳香族基团杂交，从而增强所得化合物的物理（亲脂性）和生物性质。因此，非常需要通过这种机制起作用的化合物。许多药物化学家已经在这个领域进行了研究，并开发出了优秀的新型分子。这篇综述文章汇集了这些已开发的新杂合体，以及设计策略、构效关系、生物活性和计算机研究。这篇综述还展示了烟酰胺的合成以及烟酰胺作为 GABA 重摄取抑制剂的核心作用机制。
