100390-34-9Relevant academic research and scientific papers
Antagonists of the calcium receptor I. Amino alcohol-based parathyroid hormone secretagogues
Marquis, Robert W.,Lago, Amparo M.,Callahan, James F.,Lee Trout, Robert E.,Gowen, Maxine,DelMar, Eric G.,Van Wagenen, Bradford C.,Logan, Sarah,Shimizu, Scott,Fox, John,Nemeth, Edward F.,Yang, Zheng,Roethke, Theresa,Smith, Brian R.,Ward, Keith W.,Lee, John,Keenan, Richard M.,Bhatnagar, Pradip
scheme or table, p. 3982 - 3993 (2009/12/28)
Functional screening of the former SmithKline Beecham compound collection against the human calcium receptor (CaR) resulted in the identification of the amino alcohol-based hit 2 (IC50 = 11 μM). Structure-activity studies of 2 focused on the optimization of the right- and left-hand side aromatic moieties as well as the amino alcohol linker region. Critical to the optimization of this antagonist template was the discovery that the chirality of the C-2 secondary alcohol played a key role in enhancing both CaR potency as well as selectivity over the β-adrenergic receptor subtypes. These SAR studies ultimately led to the identification of 38 (NPS 2143; SB-262470A), a potent and orally active CaR antagonist. Pharmacokinetic characterization of 38 in the rat revealed that this molecule had a large volume of distribution (11 L/kg), which resulted in a prolonged systemic exposure, protracted increases in the plasma levels of PTH, and an overall lack of net bone formation effect in a rodent model of osteoporosis.
Effects of Certain Hallucinogenic Amphetamine Analogues on the Release of Serotonin from Rat Brain Synaptosomes
Nichols, David E.,Lloyd, David H.,Hoffman, Andrew J.,Nichols, Maxine B.,Yim, George K. W.
, p. 530 - 535 (2007/10/02)
The enantiomers of 3,4-(methylenedioxy)amphetamine (MDA), p-methoxyamphetamine (PMA), and N-Me-MDA (MDMA), along with their α,α-dimethylated derivatives, were evaluated for an effect on the release of serotonin from rat whole brain synaptosomes.The amphetamine isomers were all potent in inducing the release of serotonin at bath concentrations of 1 and 10 μM but were inactive at 0.1 μM.No significant difference in isomer potency was observed at the 10-μM concentration.However, at 1 μM the (+) isomer of MDMA was more effective in inducing release than was the (-) isomer.Since it is the (+) isomer which is clinically active, this result suggests that transmitter release may play a role in the biological activity of MDMA.By contrast, the α,α-dimethyl compounds were not effective in releasing serotonin, even at the highest bath concentration.
