Key Laboratory of Structure-Based Drugs Design and Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, China.
School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, 11-68 Koshien Kuban-cho, Nishinomiya, Hyogo, 663-8179, Japan.
J Nat Med. 2018 Mar;72(2):582-587. doi: 10.1007/s11418-018-1187-9. Epub 2018 Feb 21.
Linarinic acid, (-)-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxylic acid (4a), was isolated from the ethanol extract of Linaria vulgaris Mill. In our previous study, a series of tetrahydropyrrolo[2,1-b]quinazoline derivatives 4b, 4c, 5a, 5b, 6a and 6b that were structurally related to 4a and evaluated as neuroprotective agents were synthesized. The aim of the present study was to investigate the novel features of these compounds. We examined their allergy-preventive effects using an in vivo assay system we developed previously, that monitors a decrease in blood flow in the tail vein of mice subjected to sensitization with hen egg-white lysozyme. We observed that 4a and its three derivatives, amide (6a), ester (5a), bromine (4b), and alcohol substituent (6b), showed significant allergy-preventive activities. The study confirmed the allergy-preventive activity of tetrahydropyrrolo[2,1-b]quinazoline derivatives by comprehensively monitoring the specific blood flow decrease occurring in the induction phase of allergy. This finding may aid in the development of new agents for the treatment of allergic diseases such as atopic dermatitis, allergic asthma, and hay fever.
亚麻酸，(-)-1,2,3,9-四氢吡咯并[2,1-b]喹唑啉-1-羧酸（4a），从春黄菊（Linaria vulgaris Mill.）的乙醇提取物中分离得到。在我们之前的研究中，合成了一系列与 4a 结构相关的四氢吡咯并[2,1-b]喹唑啉衍生物 4b、4c、5a、5b、6a 和 6b，并评估它们作为神经保护剂的作用。本研究的目的是研究这些化合物的新特征。我们使用我们之前开发的体内检测系统，监测对蛋清溶菌酶致敏的小鼠尾静脉血流量减少，来研究这些化合物的抗过敏作用。我们观察到 4a 及其三种衍生物酰胺（6a）、酯（5a）、溴（4b）和醇取代基（6b）具有显著的抗过敏作用。该研究通过全面监测过敏诱导阶段发生的特定血流量减少，证实了四氢吡咯并[2,1-b]喹唑啉衍生物的抗过敏活性。这一发现可能有助于开发治疗特应性皮炎、过敏性哮喘和花粉热等过敏性疾病的新药物。
