1446321-46-5

Usage

Uses

Used in Pharmaceutical Industry:
Voxelotor is used as a therapeutic agent for the treatment of sickle cell disease. It works by increasing the oxygen affinity of hemoglobin, which helps to prevent the polymerization of Hb and the subsequent formation of sickle-shaped red blood cells. This can lead to improved oxygen delivery and reduced complications associated with the disease.

Upstream product

• 387-46-2 2,6-dihydroxybenzaldehyde 
• 1446321-95-4 3-(chloromethyl)-2-(1-isopropyl-1H-pyrazol-5-yl)pyridine hydrochloride 
• 35905-85-2 2-bromonicotinic acid 
• 131747-54-1 (2-bromopyrid-3-yl)methanol 
• 524019-50-9 2-bromo-3-(((tert-butyldimethylsilyl)oxy)methyl)pyridine 
• 210037-84-6 3-{[(tert-butyldimethylsilyl)oxy]methyl}pyridine-2-carbonitrile 
• 1446321-91-0 1-(3-((tert-butyldimethylsilyloxy)methyl)pyridin-2-yl)ethanone 
• 1446321-92-1 (E)-1-(3-(((tert-butyldimethylsilyl)oxy)methyl)pyridin-2-yl)-3-(dimethylamino)prop-2-en-1-one 
• 1446321-93-2 [2-[1-(propan-2-yl)-1H-pyrazol-5-yl]pyridin-3-yl]methanol 
• 42330-59-6 (2-chloropyrid-3-yl)methanol 
• 1282518-60-8 1-isopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole 
• 70160-46-2 1,3-bis-(1-ethoxy-ethoxy)-benzene 
• 303-07-1 2,6-Dihydroxybenzoic acid 
• 2942-59-8 2-chloronicotinic acid 

Relevant academic research and scientific papers

SYNTHESIS OF A SICKLE CELL DISEASE AGENT AND INTERMEDIATES THEREOF

New processes for preparing 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5- yl)pyridin-3-yl)methoxy)benzaldehyde, an agent developed for the treatment of sickle cell disease, and intermediates thereof, are provided herein.

Preparation method of Wolkaurodol

The invention relates to a preparation method of Wolkaurodol, which comprises the following steps: reacting 6bromosalicylaldehyde serving as a raw material with 3 (chloromethyl) 2 (1isopropyl 1Hpyrazole 5) pyridine hydrochloride to obtain 2bromo 6 (((2 (1isopropyl 1Hpyrazole 5) pyridine 3) methoxy) benzaldehyde; and carrying out mild phenolic hydroxylation reaction of brominated aromatic hydrocarbon under the catalysis of RockPhos Pd G3 to obtain the Wolkaurodol. The method has the advantages of short process steps, mild reaction conditions and simple operation, and avoids the use of flammableand explosive reagents and the limitation of reaction conditions.

PROCESS AND INTERMEDIATES FOR THE PREPARATION OF VOXELOTOR

The invention relates to a process for the preparation of Voxelotor, or a salt or solvate thereof, which comprises the use of a compound of formula (I) or (I'), or a salt or solvate thereof.

PROCESS AND INTERMEDIATES FOR THE SYNTHESIS OF VOXELOTOR

The invention relates to a process for the preparation of Voxelotor, or a salt or solvate thereof, according to the following scheme (Formula 1).

PROCESS FOR SYNTHESIZING 2-HYDROXY-6-((2-(1-ISOPROPYL-1H-PYRAZOL-5-YL)-PYRIDIN-3-YL)METHOXY)BENZALDEHYDE

Disclosed herein are processes for synthesizing 2-hydroxy-6-((2-(1-isopropyl-1H- pyrazol-5-yl)-pyridin-3-yl)methoxy)benzaldehyde (also referred to herein as Compound (I)) and intermediates used in such processes. Compound (I) binds to hemoglobin and increases it oxygen affinity and hence can be useful for the treatment of diseases such as sickle cell disease.

Discovery of GBT440, an Orally Bioavailable R-State Stabilizer of Sickle Cell Hemoglobin

We report the discovery of a new potent allosteric effector of sickle cell hemoglobin, GBT440 (36), that increases the affinity of hemoglobin for oxygen and consequently inhibits its polymerization when subjected to hypoxic conditions. Unlike earlier allosteric activators that bind covalently to hemoglobin in a 2:1 stoichiometry, 36 binds with a 1:1 stoichiometry. Compound 36 is orally bioavailable and partitions highly and favorably into the red blood cell with a RBC/plasma ratio of ～150. This partitioning onto the target protein is anticipated to allow therapeutic concentrations to be achieved in the red blood cell at low plasma concentrations. GBT440 (36) is in Phase 3 clinical trials for the treatment of sickle cell disease (NCT03036813).

CRYSTALLINE 2-HYDROXY-6-((2-(1-ISOPROPYL-1H-PYRAZOL-5-YL)PYRIDIN-3-YL)METHOXY)BENZALDEHYDE ANSOLVATE SALTS

Disclosed are crystalline ansolvate salts of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde (or Compound 1), such as the hydrochloride Form I.

Crystalline Polymorphs of the Free Base of 2-Hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde

Disclosed are crystalline free base ansolvate forms of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde (or Compound 1), such as the free base Form I, Form II and Material N. Also disclosed are crystalline free base solvates of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde (or Compound 1).

Compounds and uses thereof for the modulation of hemoglobin

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.

SUBSTITUTED BENZALDEHYDE COMPOUNDS AND METHODS FOR THEIR USE IN INCREASING TISSUE OXYGENATION

Provided are substituted benzaldehydes and derivatives thereof that act as allosteric modulators of hemoglobin, methods and intermediates for their preparation, pharmaceutical compositions comprising the modulators, and methods for their use in treating disorders mediate by hemoglobin and disorders that would benefit from increased tissue oxygenation.