78072-59-0

Usage

Chemical class

Ketone

Molecular weight

150.22 g/mol

Physical state

Clear, colorless liquid

Odor

Sweet, floral

Usage in food industry

Flavoring agent

Usage in cosmetic and perfume industries

Fragrance ingredient

Usage in chemical synthesis

Precursor in the synthesis of other organic compounds

Usage in chemical reactions

Solvent

Biological and pharmacological properties

Studied for potential activities and properties

Upstream product

• 527-69-5 2-furancarbonyl chloride 
• 35061-27-9 diisopentyl cadmium 
• 56-23-5 tetrachloromethane 
• 88-14-2 2-furanoic acid 
• 334992-48-2 isopentylmagnesium iodide 
• 4548-78-1 (3-methylbutyl)magnesium bromide 
• 72667-24-4 Brenzschleimsaeurenitril 
• 110-00-9 furan 
• 646-07-1 4-Methylpentanoic acid 

Downstream Products

• 1259092-88-0 C₂₁H₂₆NO₄PS 
• 261365-11-1 MB 05032 

Relevant academic research and scientific papers

Iron-Catalyzed, Iminyl Radical-Triggered Cascade 1,5-Hydrogen Atom Transfer/(5+2) or (5+1) Annulation: Oxime as a Five-Atom Assembling Unit

By integration of iminyl radical-triggered 1,5-hydrogen atom transfer and (5+2) or (5+1) annulation processes, a series of structurally novel and interesting azepine and spiro-tetrahydropyridine derivatives have been successfully prepared in moderate to good yields. This method utilizes FeCl2 as the catalyst and readily available oximes as five-atom units, while showcasing broad substrate scope and good functional group compatibility. The annulation products can be easily converted into many valuable compounds. Moreover, DFT calculation studies are performed to provide some insights into the possible reaction mechanisms for the (5+2) and (5+1) annulations.

Photoinduced Remote Functionalisations by Iminyl Radical Promoted C?C and C?H Bond Cleavage Cascades

A photoinduced cascade strategy leading to a variety of differentially functionalised nitriles and ketones has been developed. These reactions rely on the oxidative generation of iminyl radicals from simple oximes. Radical transposition by C(sp3)?(sp3) and C(sp3)?H bond cleavage gives access to distal carbon radicals that undergo SH2 functionalisations. These mild, visible-light-mediated procedures can be used for remote fluorination, chlorination, and azidation, and were applied to the modification of bioactive and structurally complex molecules.

Preparation method of Managlinat Dialanetil

The invention discloses a preparation method of Managlinat Dialanetil. The method comprises the following steps: 1, adding ethylene glycol and triethyl orthoformate to 2-(4-methylvaleryl)-furan, and carrying out a ketalization reaction under the action of an acid catalyst to obtain a ketal mixture; 2, carrying out a phosphorylation reaction on the ketal mixture and diethyl chlorophosphate, and carrying out a deprotection reaction after the phosphorylation reaction is completed to obtain a phosphoryl lipid intermediate; 3, carrying out a bromination reaction on the phosphoryl lipid intermediate to obtain a bromide; 4, carrying out a ring closure reaction on the bromide and thiourea to obtain a thiazole intermediate; and 5, carrying out a one-pot reaction on the thiazole intermediate, TMSBr and L-alanine ethyl ester hydrochloride under the action of triphenylphosphine and dithiodipyridine, and carrying out post-treatment after the reaction is completed to obtain the Managlinat Dialanetil. The preparation method simplifies the reaction operation through optimizing step 1 and step 5, reduces the dosage of reagents and improves the reaction yield.

Discovery of a series of phosphonic acid-containing thiazoles and orally bioavailable diamide prodrugs that lower glucose in diabetic animals through inhibition of fructose-1,6-bisphosphatase

Oral delivery of previously disclosed purine and benzimidazole fructose-1,6-bisphosphatase (FBPase) inhibitors via prodrugs failed, which was likely due to their high molecular weight (>600). Therefore, a smaller scaffold was desired, and a series of phosphonic acid-containing thiazoles, which exhibited high potency against human liver FBPase (IC50 of 10-30 nM) and high selectivity relative to other 5′-adenosinemonophosphate (AMP)-binding enzymes, were discovered using a structure-guided drug design approach. The initial lead compound (30j) produced profound glucose lowering in rodent models of type 2 diabetes mellitus (T2DM) after parenteral administration. Various phosphonate prodrugs were explored without success, until a novel phosphonic diamide prodrug approach was implemented, which delivered compound 30j with good oral bioavailability (OBAV) (22-47%). Extensive lead optimization of both the thiazole FBPase inhibitors and their prodrugs culminated in the discovery of compound 35n (MB06322) as the first oral FBPase inhibitor advancing to human clinical trials as a potential treatment for T2DM.

Discovery of potent and specific fructose-1,6-bisphosphatase inhibitors and a series of orally-bioavailable phosphoramidase-sensitive prodrugs for the treatment of type 2 diabetes

Excessive glucose production by the liver coupled with decreased glucose uptake and metabolism by muscle, fat, and liver results in chronically elevated blood glucose levels in patients with type 2 diabetes. Efforts to treat diabetes by reducing glucose production have largely focused on the gluconeogenesis pathway and rate-limiting enzymes within this pathway such as fructose-1,6-bisphosphatase (FBPase). The first potent FBPase inhibitors were identified using a structure-guided drug design strategy (Erion, M. D.; et al. J. Am. Chem. Soc. 2007, 129, 15480-15490) but proved difficult to deliver orally. Herein, we report the synthesis and characterization of a series of orally bioavailable FBPase inhibitors identified following the combined discoveries of a low molecular weight inhibitor series with increased potency and a phosphonate prodrug class suitable for their oral delivery. The lead inhibitor, 10A, was designed with the aid of X-ray crystallography and molecular modeling to bind to the allosteric AMP binding site of FBPase. High potency (IC50 = 16 nM) and FBPase specificity were achieved by linking a 2-aminothiazole with a phosphonic acid. Free-energy perturbation calculations provided insight into the factors that contributed to the high binding affinity. 10A and standard phosphonate prodrugs of 10A exhibited poor oral bioavailability (0.2-11%). Improved oral bioavailability (22-47%) was achieved using phosphonate diamides that convert to the corresponding phosphonic acid by sequential action of an esterase and a phosphoramidase. Oral administration of the lead prodrug, MB06322 (30, CS-917), to Zucker Diabetic Fatty rats led to dose-dependent inhibition of gluconeogenesis and endogenous glucose production and consequently to significant blood glucose reduction.

Novel phosphorus-containing prodrug

Novel cyclic phosphoramidate prodrugs of parent drugs MH of formula I their use in delivery of drugs to the liver, their use in enhancing oral bioavailability, and their method of preparation are described.

Combination of FBPase inhibitors and insulin sensitizers for the treatment of diabetes

Pharmaceutical compositions containing an FBPase inhibitor and an insulin sensitizer are provided as well as methods for treating diabetes and diseases responding to increased glycemic control, an improvement in insulin sensitivity, a reduction in insulin levels, or an enhancement of insulin secretion.

Combination of FBPase inhibitors and antidiabetic agents useful for the treatment of diabetes

A combination therapy of at least one FBPase inhibitor and at least one other antidiabetic agent is disclosed.

Novel bisamidate phosphonate prodrugs

Novel bisamidate phosphonate prodrugs of FBPase inhibitors of the Formula IA: and their use in the treatment of diabetes and other conditions associated with elevated blood glucose.

Heteroaromatic compounds containing a phosphonate group that are inhibitors of fructose-1,6-bisphosphatase

FBPase inhibitors of the formula I and X are useful in the treatment of diabetes and other conditions associated with elevated blood glucose or excess glycogen storage.