Compounds are provided for use with glucokinase that comprise the formula:
wherein the variables are as defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using said compounds.
This present disclosure relates to compounds with ferroptosis inducing activity, a method of treating a subject with cancer with the compounds, and combination treatments with a second therapeutic agent.
Compounds of formula (I):
and salts, solvates, and physiologically functional derivatives thereof, useful for the prophylaxis or treatment of a clinical condition for which a selective β
2
-adrenoreceptor agonist is indicated, for example asthma or chronic obstructive pulmonary disease (COPD).
Identification of biaryl sulfone derivatives as antagonists of the histamine H3 receptor: Discovery of (R)-1-(2-(4′-(3-methoxypropylsulfonyl)biphenyl-4-yl)ethyl)-2-methylpyrrolidine (APD916)
作者:Graeme Semple、Vincent J. Santora、Jeffrey M. Smith、Jonathan A. Covel、Rena Hayashi、Charlemagne Gallardo、Jason B. Ibarra、Jeffrey A. Schultz、Douglas M. Park、Scott A. Estrada、Brian J. Hofilena、Brian M. Smith、Albert Ren、Marissa Suarez、John Frazer、Jeffrey E. Edwards、Ryan Hart、Erin K. Hauser、Jodie Lorea、Andrew J. Grottick
DOI:10.1016/j.bmcl.2011.11.075
日期:2012.1
The design of a new clinical candidate histamine-H-3 receptor antagonist for the potential treatment of excessive daytime sleepiness (EDS) is described. Phenethyl-R-2-methylpyrrolidine containing biphenylsulfonamide compounds were modified by replacement of the sulfonamide linkage with a sulfone. One compound from this series, 2j (APD916) increased wakefulness in rodents as measured by polysomnography with a duration of effect consistent with its pharmacokinetic properties. The identification of a suitable salt form of 2j allowed it to be selected for further development. (C) 2011 Elsevier Ltd. All rights reserved.
El-Zohry, Maher F., Phosphorus, Sulfur and Silicon and the Related Elements, 1992, vol. 66, # 14, p. 311 - 320