Hydrates of proline derivative salt and production method thereof

Abstract

The invention provides hydrates of a proline derivative salt, namely, 2.5-3.5 hydrate crystals of 3-{(2s,4s)-4-4[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidine-2-ylcarbonyl}thiazolidine 2.5 hydrobromide serving as dipeptidyl peptidases (i.e. DPP-IV) inhibitors. The crystals have the advantages of excellent stability and solubility as well as reproducibility and the invention also provides a production method of the crystals.

Description

technical field [0001] The present invention relates to novel 3-{(2s,4s)-4-4[4-(3-methyl-1-phenyl-1H-pyridines) acting as dipeptidylase-IV (i.e. DPP-IV) inhibitors Salts and solvates thereof of oxazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine, specifically relating to 3-{(2s,4s)-4-4[4-(3 -Methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine 2.5 hydrobromide 2.5 to 3.5 hydrate. Background technique [0002] DPP-IV is an amino acid sequence that recognizes that the second amino acid from the nitrogen terminal is proline (also can be alanine or hydroxyproline), and generates serine of the dipeptide Xaa-Pro (Xaa represents any amino acid, Pro represents proline). DPP-IV is known to be widely distributed in mammalian tissues, especially in blood, kidney, intestinal epithelium and placenta. [0003] DPP-IV inhibitors inhibit the inactivation of glucagon-like peptide-1 in plasma and potentiate their incretin action. Therefore, they ...

AI Technical Summary

Problems solved by technology

Therefore, these properties observed in the 3 hydrochloride salt of compound I are considered unfavorable for the development of drug products

[0006] Moreover, although the invention discloses specific salts of Compound I and its thiazolidine derivatives as example compounds, no discussion of polymorphic crystals of the example compounds has been found

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