168152-04-3Relevant articles and documents
ortho-Substituted azoles as selective and dual inhibitors of VEGF receptors 1 and 2
Kiselyov, Alexander S.,Piatnitski, Evgueni L.,Samet, Alexander V.,Kisliy, Victor P.,Semenov, Victor V.
, p. 1369 - 1375 (2007/10/03)
We have developed a series of novel potent ortho-substituted azole derivatives active against kinases VEGFR-1 and VEGFR-2. Both specific and dual ATP-competitive inhibitors of VEGFR-2 were identified. Kinase activity and selectivity could be controlled by varying the arylamido substituents at the azole ring. The most specific molecule (17) displayed >10-fold selectivity for VEGFR-2 over VEGFR-1. Compound activities in enzymatic and cell-based assays were in the range of activities for reported clinical and development candidates (IC50 30 × 10-5 cm/min) is indicative of their potential for intestinal absorption upon oral administration.
Modulators of LXR
-
, (2008/06/13)
Compounds, compositions and methods for modulating the activity of nuclear receptors are provided. In particular, heterocyclic compounds are provided for modulating the activity of nuclear receptors, including liver X receptor (LXR) and orphan nuclear receptors. In certain embodiments, the compounds are N-substituted pyridones.
Synthesis, structure-activity relationships, and pharmacokinetic properties of dihydroorotate dehydrogenase inhibitors: 2-cyano-3-cyclopropyl- 3-hydroxy. N-[3'-methyl-4'-(trifluoromethyl)phenyl]propenamide and related compounds
Kuo, Elizabeth A.,Hambleton, Philip T.,Kay, David P.,Evans, Phillip L.,Matharu, Saroop S.,Little, Edward,McDowall, Neil,Jones, C. Beth,Hedgecock, Charles J. R.,Yea, Christopher M.,Chan, A. W. Edith,Hairsine, Peter W.,Ager, Ian R.,Tully, W. Roger,Williamson, Richard A.,Westwood, Robert
, p. 4608 - 4621 (2007/10/03)
The active metabolite (2) of the novel immunosuppressive agent leflunomide (1) has been shown to inhibit the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme catalyzes the fourth step in de novo pyrimidine biosynthesis. A series of analogues of the active metabolite 2 have been synthesized. Their in vivo biological activity determined in rat and mouse delayed type hypersensitivity has been found to correlate well with their in vitro DHODH potency. The most promising compound (3) has shown activity in rat and mouse collagen (II)-induced arthritis models (ED50 = 2 and 31 mg/kg, respectively) and has shown a shorter half-life in man when compared with leflunomide. Clinical studies in rheumatoid arthritis are in progress.
N-phenyl-2-cyano-3-hydroxy-propenamides
-
, (2008/06/13)
A compound selected from the group consisting of a compound of the formula STR1 wherein R1 is selected from the group consisting of alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms and alkenyl and alkynyl of 2 to 6 carbon atoms, R2 is hydrogen or alkyl of 1 to 3 carbon atoms, Y is selected from the group consisting of STR2 Z1 and Z2 are individually selected from the group consisting of hydrogen, halogen, --NO2, --CN and alkyl of 1 to 3 carbon atoms, R3 is hydrogen or alkyl of 1 to 3 carbon atoms, m is an integer from 0 to 6, R4, R5, R6, R7 and R8 are individually selected from the group consisting of hydrogen, halogen, --CN, --NO2, alkyl, alkylthio and alkoxy of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, --COR10, --(CH2)n --CX3, --O--(CH2)n CX3 and --S--(CH2)n --CX3, R10 is selected from the group consisting of hydrogen, alkyl of 1 to 6 carbon atoms and cycloalkyl of 3 to 6 carbon atoms, n is an integer from 0 to 3, X is halogen or R6 and R7 together form --O--CH2 --O-- and their non-toxic, pharmaceutically acceptable salts with a base having anti-inflammatory and immunomodulatory activity.
