Pyrrolidine amides of pyrazolodihydropyrimidines as potent and selective KV1.5 blockers
Design and synthesis of pyrazolodihydropyrimidines as KV1.5 blockers led to the discovery of 7d as a potent and selective antagonist. This compound showed atrial selective prolongation of effective refractory period in rabbits and was selected for clinical development.
Lloyd, John,Finlay, Heather J.,Vacarro, Wayne,Hyunh, Tram,Kover, Alexander,Bhandaru, Rao,Yan, Lin,Atwal, Karnail,Conder, Mary Lee,Jenkins-West, Tonya,Shi, Hong,Huang, Christine,Li, Danshi,Sun, Huabin,Levesque, Paul
scheme or table
p. 1436 - 1439
(2010/07/02)
Diastereoselective synthesis of cyclic 1,3-aminoalcohols bearing CF3(CCl3)-groups
An aldol-type reaction of cyclic imines and cyclic lactims with carbonyl compounds activated by electron withdrawing trifluoromethyl or trichloromethyl groups proceeded without any catalyst under mild condition. β-Hydroxymethyl substituted cyclic imines or imidates are formed as a result of the reaction. The reduction of the prepared imines leads stereoselectively to the cyclic 1,3-aminoalcohols. Application of methyl trifluoropyruvate in this transformation opens an opportunity for the synthesis of γ-aminoacids derivatives which contain pyrrolidine moiety.
Shevchenko, Nikolay E.,R?schenthaler, Gerd-Volker,Mitiaev, Alexander S.,Lork, Enno,Nenajdenko, Valentine G.
scheme or table
p. 637 - 644
(2009/04/03)
New method of preparation of C2F5Li and its reactions with cyclic imines and lactims: Synthesis of α-pentafluoroethyl proline
Addition of pentafluoroethyllithium to cyclic imines leads to pentafluoroethyl substituted pyrrolidines, piperidines and azepanes while reaction of cyclic lactims gives rise to 2-pentafluoroethyl imines. Oxidative cleavage of 2-furyl-2-pentafluoroethyl pyrrolidine has been found to be an effective method for the preparation of a racemic α-pentafluoroethyl proline.
Shevchenko, Nikolay E.,Nenajdenko, Valentine G.,R?schenthaler, Gerd-Volker
p. 390 - 396
(2008/12/21)
Aqueous aldol catalysis by a nicotine metabolite
Nornicotine, an endogenous tobacco alkaloid and minor nicotine metabolite, can catalyze aldol reactions at physiological pH. Catalysis appears to be due to a covalent enamine mechanism, an unprecedented reaction with small organic molecule catalysts in aqueous buffer. Kinetic parameters for nornicotine as well as other related alkaloids were measured and demonstrate that both the pyrrolidine and pyridine rings are critical for optimal catalysis. Substrate compatibility of this catalyst and its implications in vivo are discussed. Copyright
Dickerson, Tobin J.,Janda, Kim D.
p. 3220 - 3221
(2007/10/03)
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