Rokach J, Hamel P, Hunter N R, Reader G, Rooney C S, Anderson P S, Cragoe E J, Mandel L R
J Med Chem. 1979 Mar;22(3):237-47. doi: 10.1021/jm00189a004.
Syntheses of a large number of mono- and bicyclic, as well as a few tricyclic, amidine derivatives related to 2,3,4,6,7,8,-hexahydropyrrolo[1,2-a]pyrimidine (DBN) are reported. In vitro potencies for inhibition of the enzyme indolamine N-methyltransferase (INMT) from rabbit and human lung are presented. Four bicyclic amidine derivatives and 11 monocyclic derivatives were found to be equal or superior to DBN in in vitro potencies. With the bicyclic amidines, increasing ring size or introduction of substituents reduced activity. Among the monocyclic analogues, the most potent representatives were five- or six-membered systems with an exocyclic imino group, combined with methyl of ethyl substituents on the endocyclic nitrogen. Introduction of additonal substituents decreased inhibitory potency. 2,3,5,6-Tetrahydro-8H-imidazo[2,1-c][1,4]thiazine and 3-methyl-2-iminothiazolidine have been shown to cause inhibition of lung INMT when administered orally to rabbits.
报道了大量与2,3,4,6,7,8-六氢吡咯并[1,2-a]嘧啶（DBN）相关的单环和双环以及少数三环脒衍生物的合成。给出了对兔和人肺中吲哚胺N-甲基转移酶（INMT）的体外抑制活性。发现四种双环脒衍生物和11种单环衍生物在体外活性上等于或优于DBN。对于双环脒，增大环尺寸或引入取代基会降低活性。在单环类似物中，最有效的代表是具有环外亚氨基的五元或六元体系，并在内环氮上带有甲基或乙基取代基。引入额外的取代基会降低抑制活性。已表明，2,3,5,6-四氢-8H-咪唑并[2,1-c][1,4]噻嗪和3-甲基-2-亚氨基噻唑烷经口给予兔子时会抑制肺INMT。
