title: Synthesis of 9-substituted 2,3,4,9-tetrahydro-1H-carbazole derivatives and evaluation of their anti-prion activity in TSE-infected cells.
abstract: 2,3,4,9-Tetrahydro-9-[2-hydroxy-3-(1-piperidinyl)propyl]-6-methyl-1H-carbazol-1-one (GJP14) is a novel anti-prion compound that we previously discovered by in silico screening and cellular assay. In this study, a variety of GJP14 derivatives were prepared using pyrrole derivatives, (haloalkyl)oxiranes, and amines, and their anti-prion activity was evaluated in TSE-infected cells. It was found that the tricyclic aromatic ring, a hydroxy group at the 2-position and an amino group at the 3-position of the N-propyl group were the basic requirements for anti-prion activity. The derivatives bearing an N-ortho-halobenzyl group exhibited an improved activity, and the most potent derivative was 8 times as effective as the original lead compound, GJP14.
authors: Center for Emerging Infectious Diseases, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
authors: Tsutomu
authors: T
authors: Kimura
authors: Junji
authors: J
authors: Hosokawa-Muto
authors: Kenji
authors: K
authors: Asami
authors: Toshiaki
authors: T
authors: Murai
authors: Kazuo
authors: K
authors: Kuwata
mesh_terms: D000818:Animals; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D060326:Chemistry Techniques, Synthetic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017096:Prion Diseases / Q000188:drug therapy*
chemical_list: C569929:2,3,4,9-tetrahydro-9-(2-hydroxy-3-(1-piperidinyl)propyl)-6-methyl-1H-carbazol-1-one; D002227:Carbazoles; D010880:Piperidines