75534-19-9Relevant academic research and scientific papers
Discovery and stereoselective synthesis of the novel isochroman neurokinin-1 receptor antagonist 'CJ-17,493'
Shishido, Yuji,Wakabayashi, Hiroaki,Koike, Hiroki,Ueno, Naomi,Nukui, Seiji,Yamagishi, Tatsuya,Murata, Yoshinori,Naganeo, Fumiharu,Mizutani, Mayumi,Shimada, Kaoru,Fujiwara, Yoshiko,Sakakibara, Ayano,Suga, Osamu,Kusano, Rinko,Ueda, Satoko,Kanai, Yoshihito,Tsuchiya, Megumi,Satake, Kunio
, p. 7193 - 7205 (2008/12/22)
A novel central nervous system (CNS) selective neurokinin-1 (NK1) receptor antagonist, (2S,3S)-3-[(1R)-6-methoxy-1-methyl-1-trifluoromethylisochroman-7-yl]-methylamino-2-phenylpiperidine 'CJ-17,493' (compound (+)-1), was synthesized stereoselectively using a kinetic resolution by lipase-PS as a key step. Compound (+)-1 displayed high and selective affinity (Ki = 0.2 nM) for the human NK1 receptor in IM-9 cells, potent activity in the [Sar9, Met(O2)11]SP-induced gerbil tapping model (ED50 = 0.04 mg/kg, sc) and in the ferret cisplatin (10 mg/kg, ip)-induced anti-emetic activity model (vomiting: ED90 = 0.07 mg/kg, sc), all levels of activity comparable with those of CP-122,721. In addition, compound (+)-1 exhibited linear pharmacokinetics rather than the super dose-proportionality of CP-122,721 and this result provides a potential solution for the clinical issue observed with CP-122,721.
Six-membered-ring annulation via a conjugate addition/alkylation sequence using functionalized aryllithium reagents and vinyl sulfones
Ponton, John,Helquist, Paul,Conrad, Preston C.,Fuchs, Philip L.
, p. 118 - 122 (2007/10/02)
A new method, which is a one-flask procedure involving addition of substituted aryllithium reagents 6 to vinyl sulfones 8 and 9 followed by spontaneous intramolecular alkylation of the resulting α-lithio sulfones, has been developed for the annulation of tetrahydronaphtalene moieties onto preexisting carbon frameworks.The aryllithium reagents employed in this study are the previously investigated intermediates obtained by the chemoselective lithium-halogen exchange reactions of simple as well as oxygenated o-halo-β-phenethyl halides 5.The annulation products 11 and 12 may be subjected to various further transformations which should makethe overall sequences of considerable utility in the synthesis of steroids and other polycyclic systems.
