Discovery of GBT440, an Orally Bioavailable R-State Stabilizer of Sickle Cell Hemoglobin was written by Metcalf, Brian;Chuang, Chihyuan;Dufu, Kobina;Patel, Mira P.;Silva-Garcia, Abel;Johnson, Carl;Lu, Qing;Partridge, James R.;Patskovska, Larysa;Patskovsky, Yury;Almo, Steven C.;Jacobson, Matthew P.;Hua, Lan;Xu, Qing;Gwaltney, Stephen L.;Yee, Calvin;Harris, Jason;Morgan, Bradley P.;James, Joyce;Xu, Donghong;Hutchaleelaha, Athiwat;Paulvannan, Kumar;Oksenberg, Donna;Li, Zhe. And the article was included in ACS Medicinal Chemistry Letters in 2017.Application In Synthesis of 5-Hydroxy-2-methoxylpyridine This article mentions the following:
The authors report the discovery of a new potent allosteric effector of sickle cell Hb, GBT440 I, that increases the affinity of Hb for oxygen and consequently inhibits its polymerization when subjected to hypoxic conditions. Unlike earlier allosteric activators that bind covalently to Hb in a 2:1 stoichiometry, I binds with a 1:1 stoichiometry. Compound I is orally bioavailable and partitions highly and favorably into the red blood cell with a RBC/plasma ratio of â?50. This partitioning onto the target protein is anticipated to allow therapeutic concentrations to be achieved in the red blood cell at low plasma concentrations I is in Phase 2 clin. trials for the treatment of sickle cell disease (NCT02285088). In the experiment, the researchers used many compounds, for example, 5-Hydroxy-2-methoxylpyridine (cas: 51834-97-0Application In Synthesis of 5-Hydroxy-2-methoxylpyridine).
5-Hydroxy-2-methoxylpyridine (cas: 51834-97-0) belongs to pyridine derivatives. In contrast to benzene, Pyridine’s electron density is not evenly distributed over the ring, reflecting the negative inductive effect of the nitrogen atom. Pyridine, its benzo and pyridine-based compounds play diverse roles in organic chemistry. Pyridine-based materials are valued for their optical and physical properties as well as their medical potential. Application In Synthesis of 5-Hydroxy-2-methoxylpyridine