Blank B, Krog A J, Weiner G, Pendleton R G
J Med Chem. 1980 Aug;23(8):837-40. doi: 10.1021/jm00182a005.
1,2,3,4-Tetrahydroisoquinoline-7-sulfonanilides (1-14) related to 1,2,3,4-tetrahydroisoquinoline-7-sulfonamide (21,SK&F 29661) were prepared and studied for their ability to inhibit phenylethanolamine N-methyltransferase (PNMT) in vitro. The choice of substituents on the 7-phenyl group of the sulfonanilides was based on the Topliss approach to structure-activity relationship studies. Information about the importance of an acidic hydrogen atom on the sulfonamide nitrogen atom was obtained from the preparation and testing of a tertiary N-methylsulfonanilide (15). Other THIQ's (1,2,3,4-tetrahydroisoquinolines) containing sulfur substituents in the 7 position were prepared and tested and consisted of 7-N-benzyl and 7-N-phenethyl derivatives of SK&F 29661 (16-18) and 7-(phenacylthio)-and 7-(phenacylsulfonyl)-THIQ (19 and 20). The two most potent inhibitors were the 7-p-bromo- and -chlorosulfonanilides, 2 and 6. However, neither was an effective inhibitor of norepinephrine to epinephrine conversion when tested in an in vivo mouse assay at unit doses of 25 or 100 mg/kg.
制备了与1,2,3,4 - 四氢异喹啉 - 7 - 磺酰胺（21，SK&F 29661）相关的1,2,3,4 - 四氢异喹啉 - 7 - 磺酰苯胺（1 - 14），并对其体外抑制苯乙醇胺N - 甲基转移酶（PNMT）的能力进行了研究。磺酰苯胺7 - 苯基上取代基的选择基于托普利斯结构 - 活性关系研究方法。通过制备和测试叔丁基N - 甲基磺酰苯胺（15），获得了有关磺酰胺氮原子上酸性氢原子重要性的信息。制备并测试了其他在7位含有硫取代基的四氢异喹啉（1,2,3,4 - 四氢异喹啉），包括SK&F 29661的7 - N - 苄基和7 - N - 苯乙基衍生物（16 - 18）以及7 - （苯甲酰硫基） - 和7 - （苯甲酰磺酰基） - 四氢异喹啉（19和20）。两种最有效的抑制剂是7 - 对溴 - 和 - 氯磺酰苯胺，即2和6。然而，在体内小鼠试验中以25或100 mg/kg的单位剂量测试时，它们都不是去甲肾上腺素向肾上腺素转化的有效抑制剂。
