146775-28-2Relevant articles and documents
URIDINE NUCLEOSIDE DERIVATIVES, COMPOSITIONS AND METHODS OF USE
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Paragraph 0192; 0199, (2018/04/20)
This disclosure relates to uridine nucleoside derivatives, compositions comprising therapeutically effective amounts of those nucleoside derivatives and methods of using those nucleoside derivatives or compositions in treating disorders that are responsive to compounds, such as agonists, of P2Y6 receptor, e.g., neuronal disorders, including neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease) and traumatic CNS injury, pain, Down Syndrome (DS), glaucoma and inflammatory conditions.
A series of non-quinoline cysLT1 receptor antagonists: SAR study on pyridyl analogs of Singulair
Guay, Daniel,Gauthier,Dufresne,Jones,McAuliffe,McFarlane,Metters,Prasit,Rochette,Roy,Sawyer,Zamboni
, p. 453 - 458 (2007/10/03)
The structure-activity relationship of a series of styrylpyridine analogs of MK-0476 (montelukast, Singular) is described. This work has led to the identification of a number of potent and orally active cysLT1 receptor (LTD4 receptor) antagonists including 2ab (L-733,321) as an optimized candidate.
Substituted thiopyrano[2,3,4-c,d]indoles as potent, selective, and orally active inhibitors of 5-lipoxygenase. Synthesis and biological evaluation of L-691,816
Hutchinson,Riendeau,Brideau,Chan,Delorme,Denis,Falgueyret,Fortin,Guay,Hamel,Jones,Macdonald,McFarlane,Piechuta,Scheigetz,Tagari,Therien,Girard
, p. 2771 - 2787 (2007/10/02)
Thiopyrano[2,3,4-c,d]indoles are a new class of 5-lipoxygenase (5-LO) inhibitors. SAR studies have demonstrated that the thiopyran ring, the 5- phenylpyridine substituent, and an acidic functional group on a four-carbon C-2 side chain are all required for optimal inhibitor potency. In contrast, the indolic nitrogen may be substituted with a variety of lipophilic groups. As a result of the SAR investigation, 44 (L-691,816; 5-[3-[1-(4- chlorobenzyl)-4-methyl-6-[(5-phenylpyridin-2-yl)methoxy]-4,5-dihydro-1H- thiopyrano[2,3,4-c,d]indol-2-yl]-2,2-dimethylpropyl]-1H-tetrazole) has been identified as a potent inhibitor of the 5-LO reaction both in vitro and in a range of in vivo models. Compound 44 inhibits 5-HPETE production by both rat and human 5-LO and LTB4 synthesis in human PMN leukocytes (IC50s 16, 75, and 10 nM, respectively). The mechanism of inhibition of 5-LO activity by compound 44 appears to involve the formation of a reversible deadend complex with the enzyme and does not involve reduction of the nonheme iron of 5-LO. Compound 44 is highly selective for 5-LO when compared to the inhibition of human FLAP, porcine 12-LO, and also ram seminal vesicle cyclooxygenase. In addition, 44 is orally active in a rat pleurisy model (inhibition of LTB4, ED50 = 1.9 mg/kg; 8 h pretreatment) as well as in the hyperreactive rat model of antigen-induced dyspnea (ED50 = 0.1 mg/kg; 2-h pretreatment). Excellent functional activity was also observed in both the conscious allergic monkey and sheep models of asthma. In the latter case, the functional activity observed correlated with the inhibition of urinary LTE4 excretion.
