134599-45-4Relevant articles and documents
C-3 NOVEL TRITERPENONE WITH C-17 REVERSE AMIDE DERIVATIVES AS HIV INHIBITORS
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, (2018/03/06)
The present invention relates to C-3 novel triterpenone with C-17 reverse amide compounds of Formula (I); and pharmaceutically acceptable salts thereof, wherein ring Formula (II), R1, R2, R3, R4, R5, R6, R7, 'n' and 'm' are as defined in Formula (I). The invention also relates to C-3 novel triterpenone with C-17 reverse amide derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.
Improvement of physiochemical properties of the tetrahydroazepinoindole series of farnesoid X receptor (FXR) agonists: Beneficial modulation of lipids in primates
Lundquist IV, Joseph T.,Harnish, Douglas C.,Kim, Callain Y.,Mehlmann, John F.,Unwalla, Rayomand J.,Phipps, Kristin M.,Crawley, Matthew L.,Commons, Thomas,Green, Daniel M.,Xu, Weixin,Hum, Wah-Tung,Eta, Julius E.,Feingold, Irene,Patel, Vikram,Evans, Mark J.,Lai, Kehdih,Borges-Marcucci, Lisa,Mahaney, Paige E.,Wrobel, Jay E.
experimental part, p. 1774 - 1787 (2010/08/06)
In an effort to develop orally active farnesoid X receptor (FXR) agonists, a series of tetrahydroazepinoindoles with appended, solubilizing amine functionalities were synthesized. The crystal structure of the previously disclosed FXR agonist, 1 (FXR-450), aided in the design of compounds with tethered solubilizing functionalities designed to reach the solvent cavity around the hFXR receptor. These compounds were soluble in 0.5% methylcellulose/2% Tween-80 in water (MC/T) for oral administration. In vitro and in vivo optimization led to the identification, of 14dd and 14cc, which in a dosedependent fashion regulated low density lipoprotein, cholesterol (LDLc) in low density lipoprotein receptor knockout (LDLR-/-) mice. Compound 14cc was dosed in female rhesus monkeys for 4 weeks at 60 mg/kg daily in MC/T vehicle. After 7 days, triglyceride (TG) levels and very low density lipoprotein cholesterol (VLDLc) levels were significantly decreased and LDLc was decreased 63%. These data are the first to demonstrate the dramatic lowering of serum LDLc levels by a FXR agonist in primates and supports the potential utility of 14cc in treating dyslipidemia in humans beyond just TG lowering.
Falcipain inhibitors: Optimization studies of the 2-pyrimidinecarbonitrile lead series
Coterón, Jose M.,Catterick, David,Castro, Julia,Chaparro, María J.,Díaz, Beatriz,Fernández, Esther,Ferrer, Santiago,Gamo, Francisco J.,Gordo, Mariola,Gut, Jiri,De Las Heras, Laura,Legac, Jennifer,Marco, Maria,Miguel, Juan,Mu?oz, Vicente,Porras, Esther,De La Rosa, Juan C.,Ruiz, Jose R.,Sandoval, Elena,Ventosa, Pilar,Rosenthal, Philip J.,Fiandor, Jose M.
supporting information; experimental part, p. 6129 - 6152 (2010/10/21)
Falcipain-2 and falcipain-3 are papain-family cysteine proteases of the malaria parasite Plasmodium falciparum that are responsible for host hemoglobin hydrolysis to provide amino acids for parasite protein synthesis. Different heteroarylnitrile derivatives were studied as potential falcipain inhibitors and therefore potential antiparasitic lead compounds, with the 5-substituted-2- cyanopyrimidine chemical class emerging as the most potent and promising lead series. Through a sequential lead optimization process considering the different positions present in the initial scaffold, nanomolar and subnanomolar inhibitors at falcipains 2 and 3 were identified, with activity against cultured parasites in the micromolar range. Introduction of protonable amines within lead molecules led to marked improvements of up to 1000 times in activity against cultured parasites without noteworthy alterations in other SAR tendencies. Optimized compounds presented enzymatic activities in the picomolar to low nanomolar range and antiparasitic activities in the low nanomolar range.