877264-27-2Relevant articles and documents
Design and synthesis of 4-heteroaryl 1,2,3,4-tetrahydroisoquinolines as triple reuptake inhibitors
Liu, Shuang,Zha, Congxiang,Nacro, Kassoum,Hu, Min,Cui, Wenge,Yang, Yuh-Lin,Bhatt, Ulhas,Sambandam, Aruna,Isherwood, Matthew,Yet, Larry,Herr, Michael T.,Ebeltoft, Sarah,Hassler, Carla,Fleming, Linda,Pechulis, Anthony D.,Payen-Fornicola, Anne,Holman, Nicholas,Milanowski, Dennis,Cotterill, Ian,Mozhaev, Vadim,Khmelnitsky, Yuri,Guzzo, Peter R.,Sargent, Bruce J.,Molino, Bruce F.,Olson, Richard,King, Dalton,Lelas, Snjezana,Li, Yu-Wen,Johnson, Kim,Molski, Thaddeus,Orie, Anitra,Ng, Alicia,Haskell, Roy,Clarke, Wendy,Bertekap, Robert,O'Connell, Jonathan,Lodge, Nicholas,Sinz, Michael,Adams, Stephen,Zaczek, Robert,Macor, John E.
, p. 760 - 765 (2014/07/22)
(Chemical Equation Presented) A series of 4-bicyclic heteroaryl 1,2,3,4-tetrahydroisoquinoline inhibitors of the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT) was discovered. The synthesis and structure-activity relationship (SAR) of these triple reuptake inhibitors (TRIs) will be discussed. Compound 10i (AMR-2), a very potent inhibitor of SERT, NET, and DAT, showed efficacy in the rat forced-swim and mouse tail suspension models with minimum e ffective doses of 0.3 and 1 mg/kg (po), respectively. At efficacious doses in these assays, 10i exhibited substantial occupancy levels at the three transporters in both rat and mouse brain. The study of the metabolism of 10i revealed the formation of a significant active metabolite, compound 13.
Aryl- and heteroaryl-substituted tetrahydroisoquinolines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin
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Page/Page column 140, (2008/06/13)
The compounds of the present invention are represented by the chemical structure found in Formula (I): wherein: the carbon atom designated * is in the R or S configuration; and X is a fused bicyclic carbocycle or heterocycle selected from the group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, benzotriazolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, indenyl, indanyl, dihydrobenzocycloheptenyl, tetrahydrobenzocycloheptenyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, indolinyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 2H-chromenyl, 4H-chromenyl, and a fused bicyclic carbocycle or fused bicyclic heterocycle optionally substituted with substituents (1 to 4 in number) as defined in R14; with R1, R2, R3, R4, R5, R6, R7, R8, and R14 defined herein.
