170019-22-4Relevant academic research and scientific papers
Metabolism-guided discovery of a potent and orally bioavailable urea-based calcimimetic for the treatment of secondary hyperparathyroidism
Wehn, Paul M.,Harrington, Paul E.,Carlson, Timothy J.,Davis, James,Deprez, Pierre,Fotsch, Christopher H.,Grillo, Mark P.,Lu, Jenny Ying-Lin,Morony, Sean,Pattabiraman, Kanaka,Poon, Steve F.,Reagan, Jeff D.,St. Jean Jr., David J.,Temal, Taoues,Wang, Minghan,Yang, Yuhua,Henley III, Charles,Lively, Sarah E.
, p. 6625 - 6628 (2014/01/06)
A series of urea based calcimimetics was optimized for potency and oral bioavailability. Crucial to this process was overcoming the poor pharmacokinetic properties of lead thiazole 1. Metabolism-guided modifications, characterized by the use of metabolite identification (ID) and measurement of time dependent inhibition (TDI) of CYP3A4, were essential to finding a compound suitable for oral dosing. Calcimimetic 18 exhibited excellent in vivo potency in a 5/6 nephrectomized rat model and cross-species pharmacokinetics.
Controlled mono- and double-Heck reaction catalyzed by a dicarbene dipalladium complex
Li, Yunfei,Liu, Gang,Cao, Changsheng,Wang, Shuzhan,Li, Yuling,Pang, Guangsheng,Shi, Yanhui
, p. 6241 - 6250 (2013/07/27)
The phosphine-free mono- and double-Heck reaction of terminal olefins with electron-deficient and electron-rich aryl halides (iodides and bromides) is described. These reactions are catalyzed by the dicarbene dipalladium complex 1 by controlling the stoichiometry of the aryl halide and the olefine, the loading of the palladium catalyst, as well as using different base, and with or without additive. The procedure of double-Heck reaction allows β,β- diarylation and β,β′-diarylation of terminal olefins and affords trisubstituted olefins in good to excellent yields.
Palladium-catalyzed double arylations of terminal olefins in acetic acid
Xu, Daichao,Lu, Chunxin,Chen, Wanzhi
experimental part, p. 1466 - 1474 (2012/03/08)
A palladium-catalyzed Heck diarylation of terminal olefins under ligand-free conditions in acetic acid is described. This procedure allows double arylation of terminal olefins affording trisubstituted olefins in good to excellent yields. The methodology is applicable to the coupling of both electron-deficient and electron-rich aryl iodides leading to symmetrical and unsymmetrical β,β-diarylated alkenes.
Anticonvulsant and central nervous system-depressing bis(fluorophenyl)alkylamides and their uses
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, (2008/06/13)
Bis(Fluorophenyl)alkylamides have been chemically synthesized which possess beneficial pharmacological properties (e.g., anticonvulsant activity) useful for the treatment of neurological diseases or disorders, such as, for example, epilepsy, convulsions, and seizure disorders. The preferred compounds of the invention also cause little sedation and have high therapeutic and protective indices in animal models of epilepsy. These compounds further possess long pharmacological half-lives, which, in practical clinical therapeutic application, should translate into once-a-day dosing, of great benefit to patients suffering from these diseases and/or disorders. These compounds may also be of further clinical utility in the treatment of other diseases and disorders of the central and peripheral nervous systems, or diseases or disorders affected by them, including, but not limited to, spasticity, skeletal muscle spasms and pain, restless leg syndrome, anxiety and stress, and bipolar disorder.
Compounds active at a novel site on receptor-operated calcium channels useful for treatment of neurological disorders and diseases
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, (2008/06/13)
Method and compositions for treating a patient having a neurological disease or disorder, such as stroke, head trauma, spinal cord injury, spinal cord ischemia, ischemia- or hypoxia-induced nerve cell damage, epilepsy, anxiety, neuropsychiatric or cogniti
Compounds active at a novel site on receptor-operated calcium channels useful for treatment of neurological disorders and diseases
-
, (2008/06/13)
Method and compositions for treating a patient having a neurological disease or disorder, such as stroke, head trauma, spinal cord injury, epilepsy, anxiety, or neurodegenerative diseases such as Alzheimer's Disease, Huntington's Disease, Parkinson's Dise
