463976-07-0

Basic information

• Product Name: 6-(5-Chloro-3-methyl-1-benzofuran-2-ylsulfonyl)pyridazin-3(2H)-one
• CAS NO: 463976-07-0
• Molecular Formula: C₁₃H₉ClN₂O₄S
• Molecular Weight: 324.74468
• Mol File: 463976-07-0.mol

Chemical Properties

• CAS DataBase Reference: 6-(5-Chloro-3-methyl-1-benzofuran-2-ylsulfonyl)pyridazin-3(2H)-one(CAS DataBase Reference)
• NIST Chemistry Reference: 6-(5-Chloro-3-methyl-1-benzofuran-2-ylsulfonyl)pyridazin-3(2H)-one(463976-07-0)
• EPA Substance Registry System: 6-(5-Chloro-3-methyl-1-benzofuran-2-ylsulfonyl)pyridazin-3(2H)-one(463976-07-0)

Safety Data

• Hazardous Substances Data: 463976-07-0(Hazardous Substances Data)

Upstream product

• 1125-41-3 5-chloro-3-methylbenzofuran 
• 463976-08-1 5-chloro-2-mercapto-3-methylbenzofuran 
• 463976-10-5 6-(5-chloro-3-methylbenzofuran-2-sulfenyl)-2H-pyridazin-3-one 
• 463976-11-6 6-(5-chloro-3-methylbenzofuran-2-sulfonyl)-3-methoxypyridazine 
• 463976-10-5 6-(5-chloro-3-methyl-benzofuran-2-ylsulfanyl)-pyridazin-3-ol 
• 463976-90-1 6-(5-chloro-3-methylbenzofuran-2-sulfenyl)-3-methoxypyridazine 

Downstream Products

• 1125-41-3 5-chloro-3-methylbenzofuran 

Relevant articles and documents

SPRAY DRIED FORMULATION

Pharmaceutical compositions comprising a poorly water soluble ionizable drug, a cationic species and a dispersion polymer are disclosed, together with a process for forming the compositions. The neutral form of the drug has (i) a solubility of less than 1 mg/mL in aqueous solution at a pH between 6 and 7, (ii) a solubility of less than 20 mg/mL in a volatile organic solvent, and (iii) an acidic pKa value of greater than 5. At least 90 wt% of the drug in the solid dispersion being in a non-crystalline form. The drug, the cationic species, and the dispersion polymer constitute at least 80 wt% of the solid dispersion.

A novel series of non-carboxylic acid, non-hydantoin inhibitors of aldose reductase with potent oral activity in diabetic rat models: 6-(5-Chloro-3- methylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one and congeners

Discovery of a highly selective, potent, and safe non-carboxylic acid, non-hydantoin inhibitor of aldose reductase (AR) capable of potently blocking the excess glucose flux through the polyol pathway that prevails under diabetic conditions has been a long-standing challenge. In response, we did high-throughput screening of our internal libraries of compounds and identified 6-phenylsulfonylpyridazin-2H-3-one, 8, which showed modest inhibition of AR, both in vitro and in vivo. Initial structure-activity relationships concentrated on phenyl substituents and led to 6-(2,4-dichlorophenylsulfonyl)-2/f-pyridazin- 3-one, 81, which was more potent than 8, both in vitro and in vivo. Incorporation of extant literature findings with other aldose reductase inhibitors, including zopolrestat, resulted in the title inhibitor, 19m, which is one of the most potent and highly selective non-carboxylic acid, non-hydantoin inhibitors of AR yet described (IC50, 1 nM; ED 90 vs sciatic nerve sorbitol and fructose, respectively, 0.8 and 4.0 mg/kg). In rats, its oral bioavailability is 98% and it has a favorable plasma t1/2 (26 ± 3 h).

Process and intermediates for pyridazinone antidiabetic agents

The present invention relates to a process for preparing pyridazinone aldose reductase inhibitors which are useful in the prevention and/or treatment of diabetic complications such as diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic microangiopathy and diabetic macroangiopathy in mammals. The invention also relates to novel intermediates useful in preparing those aldose reductase inihibitors.

A highly selective, non-hydantoin, non-carboxylic acid inhibitor of aldose reductase with potent oral activity in diabetic rat models: 6-(5-chloro-3-methylbenzofuran-2-sulfonyl)-2-H-pyridazin-3-one

We report here on the discovery path that led to a structurally unprecedented non-hydantoin, non-carboxylic acid aldose reductase inhibitor, 24, which shows remarkably potent oral activity in normalizing elevated sorbitol levels and, more significantly, f

Pyridazinone aldose reductase inhibitors

The present invention relates to novel pyridazinone compounds, pharmaceutical compositions comprising those compounds and to methods of using such compounds and compositions to inhibit aldose reductase, lower sorbitol levels and, thus, lower fructose levels, and/or treat or prevent diabetic complications such as diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic microangiopathy and diabetic macroangiopathy in mammals. This invention also relates to methods of affording cardioprotection to subjects not suffering from diabetes. This invention also relates to pharmaceutical compositions and kits comprising a combination of an aldose reductase inhibitor (ARI) of this invention and a sorbitol dehydrogenase inhibitor and to methods of using such compositions or kits to treat or prevent the above diabetic complications in mammals. This invention also relates to other combinations with the ARIs of this invention, including combinations with adendsine agonists; NHE-1 inhibitors; glycogen phosphorylase inhibitors; selective serotonin reuptake inhibitors; GABA agonists; antihypertensive agents; 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors; phosphodiesterase-5 inhibitors; and to glucose lowering agents.