34 results about "Propanoic Acid Derivatives" patented technology

The present invention provides a novel compound represented by the formula (I) wherein each symbol is as defined in the specification, a salt thereof and a prodrug thereof having a superior GPR40 receptor function modulating action, which can be used as an insulin secretagogue, an agent for the prophylaxis or treatment of diabetes and the like. They unexpectedly show superior GPR40 receptor agonist activity, and also show superior properties as a pharmaceutical product, such as stability and the like. Thus, they can be safe and useful pharmaceutical agents for the prophylaxis or treatment of GPR40 receptor related diseases in mammals.

A compound of formula (I) or a salt thereof are provided:

wherein R¹, X and R³ are defined in the specification, useful in the treatment of disorders mediated by KMO such as acute pancreatitis, chronic kidney disease, other conditions associated with systemic inflammatory response syndrome (SIRS), Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, amylotrophic lateral sclerosis (ALS), depression, schizophrenia, sepsis, cardiovascular shock, severe trauma, acute lung injury, acute respiratory distress syndrome, acute cholecystitis, severe burns, pneumonia, extensive surgical procedures, ischemic bowel, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure.

The invention discloses a 2-(4-methoxyphenoxy) propionic acid derivative with a sweetness inhibiting effect and an industrial production method of the 2-(4-methoxyphenoxy) propionic acid derivative. The structural general formula is shown in the specification, in the formula, R represents C1-C4 alkyl, C1-C4 alkoxy, nitryl or halogen atoms, and X represents hydrogen atoms or C1-C3 alkyl. The preparation method comprises the following steps: mixing p-methoxy substituted phenol, ethyl 2-bromoalkanoate and potassium carbonate, reacting in dimethylformamide, and filtering; adding water and an organic phase into the filtrate, carrying out liquid separation treatment, and evaporating to remove the organic phase to obtain an ester compound; and adding the obtained ester and sodium hydroxide into ethanol, carrying out reflux reaction, acidifying, extracting, recrystallizing and the like to obtain the 2-(4-methoxyphenoxy) propionic acid derivative. The derivative is a brand-new sweetness inhibiting compound and has a good sweetness inhibiting effect on cane sugar, the industrial method is mild in reaction condition, the temperature does not exceed 100 DEG C, separation and purification are simple, and the product purity is high.

The present invention provides a process for preparing 3-amino-2-hydroxypropionic acid derivatives (1) which does not use dangerous reagents, is economically advantageous, and is suitable for an industrial production, which process comprises:

• • treating N-protected-3-amino-2-hydroxypropionic acid derivatives (2) having a steric configuration at 2-position carbon reverse to that of derivatives (1) with a leaving group-introducing agent to convert into N-protected-3-aminopropionic acid derivatives (3),
  • then treating the derivatives with a basic substance to convert into substituted-3-amino-2-hydroxypropionic acid derivatives (4) having an inverted steric configuration at 2-position carbon,
  • and then converting the derivatives into 3-amino-2-hydroxypropionic acid derivatives (1).

The present invention relates to highly enantiomerically pure lactam-substituted propanoic acid derivatives and methods of making and using therefor. The invention involves a multi-step synthesis to produce the lactam compounds. In one step of the reaction sequence, asymmetric hydrogenation of a lactam-enamide was performed to produce an intermediate that can ultimately be converted to a series of pharmaceutical compounds. The invention also contemplates the in situ synthesis of an intermediate of the multi-step synthesis, which provides economic advantages to the overall synthesis of the lactam compounds.

The invention relates to a synthesis method of an N-Fmoc-3-aminopropionic acid derivative. The method comprises the following steps: (1) reacting a compound (I) with a compound (II) in the presence of a solvent and alkali to obtain a compound (III); (2) carrying out a hydrolysis reaction on the a compound (III) to obtain a compound (IV); and (3) reacting the compound (IV) with fluorenylmethoxycarbonyl succinimide in the presence of the alkali and the solvent to obtain a compound (V) that is the N-Fmoc-3-aminopropionic acid derivative. A process route of the N-Fmoc-3-aminopropionic acid derivative is developed in the invention, makes up the blank of the synthesis method of the substance in the prior art, and the synthesis method is simple, few in steps, high in product yield, easily available in adopted raw materials and low in synthesis cost.

The problem to be solved by the present invention is to provide a compound suitable for a pharmaceutical composition, specifically a pharmaceutically composition for treating nocturia.

The inventors have assumed that inhibition of nocturnal activity of placental leucine aminopeptidase (P-LAP), i.e. aminopeptidase that cleaves AVP, would maintain and/or increase an endogenous AVP level to enhance the antidiuretic effect, which would contribute to a decreased number of nocturnal voids, and have extensively studied compounds which inhibit P-LAP. As a result, the inventors have found that (2R)-3-amino-2-(bi-cyclic pyridylmethyl)-2-hydroxy-propanoic acid derivatives have excellent P-LAP inhibitory activity. The inventors have evaluated antidiuretic effects in water-loaded rats and have found that the compounds increase endogenous AVP levels by inhibiting P-LAP and consequently reduce urine production. The present invention therefore provides compounds expected to be used as an agent for treating nocturia based on P-LAP inhibition.