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.Quality Control of 3,5-Dimethoxyisonicotinaldehyde 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, 3,5-Dimethoxyisonicotinaldehyde (cas: 204862-70-4Quality Control of 3,5-Dimethoxyisonicotinaldehyde).
3,5-Dimethoxyisonicotinaldehyde (cas: 204862-70-4) belongs to pyridine derivatives. Pyridine has a dipole moment and a weaker resonant stabilization than benzene (resonance energy 117 kJ·molâ? in pyridine vs. 150 kJ·molâ? in benzene). Halopyridines are particularly attractive synthetic building blocks in a variety of cross-coupling methods, including the Suzuki-Miyaura cross-coupling reaction.Quality Control of 3,5-Dimethoxyisonicotinaldehyde