Al-Horani, Rami A. published the artcilePotent direct inhibitors of factor Xa based on the tetrahydroisoquinoline scaffold, Application In Synthesis of 16909-09-4, the publication is European Journal of Medicinal Chemistry (2012), 771-783, database is CAplus and MEDLINE.
Direct inhibition of coagulation factor Xa (FXa) carries significant promise for developing effective and safe anticoagulants. Although a large number of FXa inhibitors have been studied, each can be classified as either possessing a highly flexible or a rigid core scaffold. The authors reasoned that an intermediate level of flexibility would provide high selectivity for FXa, considering that its active site is less constrained in comparison to thrombin and more constrained as compared to trypsin. They studied several core scaffolds including 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid for direct FXa inhibition. Using a genetic algorithm-based docking and scoring approach, a promising candidate I was identified, synthesized, and found to inhibit FXa with a Ki of 28 ¦ÌM. Optimization of derivative I resulted in the design of a potent dicarboxamide II, which displayed a Ki of 135 nM. Dicarboxamide II displayed at least 1852-fold selectivity for FXa inhibition over other coagulation enzymes and doubled PT and aPTT of human plasma at 17.1 ¦ÌM and 20.2 ¦ÌM, resp., which are comparable to those of clin. relevant agents. Dicarboxamide II is expected to serve as an excellent lead for further anticoagulant discovery.
European Journal of Medicinal Chemistry published new progress about 16909-09-4. 16909-09-4 belongs to catalysis-chemistry, auxiliary class Alkenyl,Carboxylic acid,Benzene,Ether, name is (E)-3-(2,4-Dimethoxyphenyl)acrylic acid, and the molecular formula is C11H12O4, Application In Synthesis of 16909-09-4.
Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia