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JNJ-7925476 is a TRI antidepressant currently under development by Johnson & Johnson. These molecules were first prepared by Bruce E. Maryanoff, et al. during the late 1970s – 1980's. and is known as a pyrroloisoquinoline, that is benzhydryl-containing. Incorporating the pyrrolidino ring onto the THIQ scaffolding markedly improves potency, although this only works for one of the available diastereo/enantiomers. JNJ-7925476 is a racemic preparation of the more potent diastereomer. The eutomer, JNJ-39836966 has (6''R'',10b''S'')-stereochemistry whereas the distomer JNJ-39836732 will have (6''S'',10b''R'')-stereochemistry. The compounds depicted appear to be ''cis'' but Maryanoff and coworkers are of the opinion that it is ''trans''.〔 (see abstract) The reason for this is not known because it was referred to as "cis" to begin with, only reassigning it later. Cyclohexane conformation ==In-vitro characterization== Ki values (nM) for JNJ-7925476 and its constituent enantiomers (JNJ-39836966 and JNJ-39836732) In vitro, JNJ-7925476 is ~18-fold selective for the hSERT (0.9 nM) over the hNET (16.6 nM). Ex vivo transporter occupancy of JNJ-7925476 (in rat brain) followed the ordering priority: NET > SERT > DAT. This is consistent with the results cited earlier for rat brains (see SAR table dated 1987). However, there is relatively poor correlation between the in vitro data presented for rats brains vs what was reported at the human transporters. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「JNJ-7925476」の詳細全文を読む スポンサード リンク
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