Reference of 10288-72-9, New Advances in Chemical Research, May 2021. The dynamic chemical diversity of the numerous elements, ions and molecules that constitute the basis of life provides wide challenges and opportunities for research. In a document type is Article, and a compound is mentioned, 10288-72-9, Name is 6-Hydroxy-1,4-benzodioxane, introducing its new discovery.
alpha4beta1 and alpha4beta7 integrins are key regulators of physiologic and pathologic responses in inflammation and autoimmune disease. The effectiveness of anti-integrin antibodies to attenuate a number of inflammatory/immune conditions provides a strong rationale to target integrins for drug development. Important advances have been made in identifying potent and selective candidates, peptides and peptidomimetics, for further development. Herein, we report the discovery of a series of novel N-benzoyl-L-biphenylalanine derivatives that are potent inhibitors of alpha4 integrins. The potency of the initial lead compound (1: IC50 alpha4beta7/alpha4beta1 =5/33 muM) was optimized via sequential manipulation of substituents to generate low nM, orally bioavailable dual alpha4beta1/alpha4beta7 antagonists. The SAR also led to the identification of several subnanomolar antagonists (134, 142, and 143). Compound 81 (TR-14035; IC50 alpha4beta7/alpha4beta1 =7/87 nM) has completed Phase I studies in Europe. The synthesis, SAR and biological evaluation of these compounds are described.
I am very proud of our efforts over the past few months and hope to 10288-72-9 help many people in the next few years. Reference of 10288-72-9