67529-18-4Relevant academic research and scientific papers
Synthesis of (-)-(S, S)-clemastine by invertive N → C aryl migration in a lithiated carbamate
Fournier, Anne M.,Brown, Robert A.,Farnaby, William,Miyatake-Ondozabal, Hideki,Clayden, Jonathan
, p. 2222 - 2225 (2010)
The first enantioselective synthesis of the antihistamine agent clemastine, as its (S,S)-stereoisomer, has been achieved by ether formation between a proline-derived chloroethylpyrrolidine and an enantiomerically enriched tertiary alcohol. The tertiary alcohol was formed from the carbamate derivative of α-methyl-p-chlorobenzyl alcohol by invertive aryl migration on lithiation. The (S,S)-stereochemistry of the product confirms the invertive nature of the rearrangement.
Design, synthesis, and biological evaluation of 3,4-dihydroquinolin-2(1 H)-one and 1,2,3,4-tetrahydroquinoline-based selective human neuronal nitric oxide synthase (nNOS) inhibitors
Ramnauth, Jailall,Speed, Joanne,Maddaford, Shawn P.,Dove, Peter,Annedi, Subhash C.,Renton, Paul,Rakhit, Suman,Andrews, John,Silverman, Sarah,Mladenova, Gabriela,Zinghini, Salvatore,Nair, Sheela,Catalano, Concettina,Lee, David K.H.,De Felice, Milena,Porreca, Frank
scheme or table, p. 5562 - 5575 (2011/10/05)
Neuronal nitric oxide synthase (nNOS) inhibitors are effective in preclinical models of many neurological disorders. In this study, two related series of compounds, 3,4-dihydroquinolin-2(1H)-one and 1,2,3,4- tetrahydroquinoline, containing a 6-substituted thiophene amidine group were synthesized and evaluated as inhibitors of human nitric oxide synthase (NOS). A structure-activity relationship (SAR) study led to the identification of a number of potent and selective nNOS inhibitors. Furthermore, a few representative compounds were shown to possess druglike properties, features that are often difficult to achieve when designing nNOS inhibitors. Compound (S)-35, with excellent potency and selectivity for nNOS, was shown to fully reverse thermal hyperalgesia when given to rats at a dose of 30 mg/kg intraperitonieally (ip) in the L5/L6 spinal nerve ligation model of neuropathic pain (Chung model). In addition, this compound reduced tactile hyperesthesia (allodynia) after oral administration (30 mg/kg) in a rat model of dural inflammation relevant to migraine pain.
