Kaur Jaskiran, Ghosh Narendra Nath, Chandra Ramesh
Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Chem Pharm Bull (Tokyo). 2004 Mar;52(3):316-21. doi: 10.1248/cpb.52.316.
A new series of N-substituted bis-(tetrahydropapaverine) ring systems have been synthesised in expectation of better antispasmodic activity in comparison with papaverine. The synthesis of the targeted heterocycles is described along with a discussion of their structure activity relationship. The general synthetic methods of bis-(tetrahydropapaverine) analogues involve tetrahydropapaverine, various piperazines, diisocyanates and diisothiocyanates as starting materials. Pharmacological evaluation involves the in vitro antispasmodic activity on a freshly removed guinea pig ileum using a force displacement transducer amplifier connected to a physiograph. Among the analogues synthesized in the present study, N,N'-bis-[2-carbamoyl-1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolinyl]piperazine (22), was found to be the most potent muscle relaxant (IC(50): 0.31 microM).
人们合成了一系列新的N-取代双（四氢罂粟碱）环系统，期望其与罂粟碱相比具有更好的抗痉挛活性。文中描述了目标杂环的合成过程，并讨论了它们的构效关系。双（四氢罂粟碱）类似物的一般合成方法是以四氢罂粟碱、各种哌嗪、二异氰酸酯和二异硫氰酸酯为起始原料。药理评估包括使用连接到生理记录仪的力位移换能器放大器，对新鲜取出的豚鼠回肠进行体外抗痉挛活性测试。在本研究合成的类似物中，N,N'-双-[2-氨基甲酰基-1-(3,4-二甲氧基苄基)-6,7-二甲氧基-1,2,3,4-四氢异喹啉基]哌嗪（22）被发现是最有效的肌肉松弛剂（IC(50)：0.31 microM）。
