401564-30-5

Usage

Uses

Used in Medicinal Chemistry Research:
(2S,4R)-4-Hydroxy-2-(3-thiazolidinylcarbonyl)-1-pyrrolidinecarboxylic acid tert-butyl ester is used as a precursor in the synthesis of Pioglitazone and related compounds for medicinal chemistry research. Its protective tert-butyl ester group allows for the controlled modification of the molecule, facilitating the development of new therapeutic agents.
Used in Drug Development for Diabetes and Metabolic Disorders:
In the pharmaceutical industry, (2S,4R)-4-Hydroxy-2-(3-thiazolidinylcarbonyl)-1-pyrrolidinecarboxylic acid tert-butyl ester is utilized as a key intermediate in the development of novel antidiabetic drugs. Its potential therapeutic applications extend to the treatment of type 2 diabetes and other metabolic disorders, offering a promising avenue for improving patient outcomes and managing blood sugar levels effectively.

Upstream product

• 504-78-9 1,3-thiazolidine 
• 13726-69-7 (2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid 
• 40350-82-1 1-(t-butoxycarbonyl)-4-hydroxyproline 
• 144-55-8 sodium hydrogencarbonate 

Downstream Products

• 401564-36-1 (2S)-4-oxo-2-(3-thiazolidinylcarbonyl)-1-pyrrolidinecarboxylic acid tert-butyl ester 
• 401565-01-3 3-[(2S,4S)-1-tert-butoxycarbonyl-4-(3,4-dicyanophenyl)amino-2-pyrrolidinylcarbonyl]-1,3-thiazolidine 
• 401565-12-6 3-[(2S,4S)-1-tert-butoxycarbonyl-4-(2-chloro-4-cyanophenyl)amino-2-pyrrolidinylcarbonyl]-1,3-thiazolidine 
• 401565-02-4 3-[(2S,4S)-1-tert-butoxycarbonyl-4-(3-chloro-4-cyanophenyl)amino-2-pyrrolidinylcarbonyl]-1,3-thiazolidine 
• 401564-98-5 3-[(2S,4S)-1-tert-butoxycarbonyl-4-(4-methanesulfonylphenyl)amino-2-pyrrolidinylcarbonyl]-1,3-thiazolidine 
• 401565-13-7 3-[(2S,4S)-1-tert-butoxycarbonyl-4-(3-chloro-4-methoxyphenyl)amino-2-pyrrolidinylcarbonyl]-1,3-thiazolidine 
• 401564-96-3 3-[(2S,4S)-1-tert-butoxycarbonyl-4-(4-cyanophenyl)amino-2-pyrrolidinylcarbonyl]-1,3-thiazolidine 
• 401564-97-4 3-[(2S,4S)-1-tert-butoxycarbonyl-4-(4-nitrophenyl)amino-2-pyrrolidinylcarbonyl]-1,3-thiazolidine 
• 401564-99-6 3-[(2S,4S)-1-tert-butoxycarbonyl-4-(2-cyanophenyl)amino-2-pyrrolidinylcarbonyl]-1,3-thiazolidine 

Relevant academic research and scientific papers

Fused bicyclic heteroarylpiperazine-substituted l-prolylthiazolidines as highly potent DPP-4 inhibitors lacking the electrophilic nitrile group

Hypoglycemic agents with a mechanism of depeptidyl peptidase IV (DPP-4) inhibition are suitable for once daily oral dosing. It is difficult to strike a balance between inhibitory activity and duration of action in plasma for inhibitors bearing an electrophilic nitrile group. We explored fused bicyclic heteroarylpiperazine substituted at the γ-position of the proline structure in the investigation of l-prolylthiazolidines lacking the electrophilic nitrile. Among them, 2-trifluoroquinolyl compound 8g is the most potent, long-lasting DPP-4 inhibitor (IC50 = 0.37 nmol/L) with high selectivity against other related peptidases. X-ray crystal structure determination of 8g indicates that CH-π interactions generated between the quinolyl ring and the guanidinyl group of Arg358 enhances the DPP-4 inhibitory activity and selectivity.

[(S)-γ-(4-Aryl-1-piperazinyl)-l-prolyl]thiazolidines as a novel series of highly potent and long-lasting DPP-IV inhibitors

In the search for an inhibitor of dipeptidyl peptidase IV (DPP-IV) highly potent both in vitro and in vivo, we synthesized a series of l-prolylthiazolidine-based DPP-IV inhibitors having 4-arylpiperazine or 4-arylpiperidine at the γ-position of the proline structure. Of these compounds, the 4-(5-nitro-2-pyridyl)piperazine analog 21e showed a sub-nanomolar (IC50 = 0.92 nmol/L) DPP-IV inhibitory activity and a long-lasting in vivo DPP-IV inhibition profile.

[(S)-γ-(Arylamino)prolyl]thiazolidine compounds as a novel series of potent and stable DPP-IV inhibitors

Dipeptidyl peptidase-IV (DPP-IV) inhibitors, or glucagon-like peptide-1 (GLP-1) enhancers, are looked to as a potential new class of antidiabetic agents. In particular, potent and long-acting inhibitors might offer advantages in exploiting DPP-IV inhibition. The series of [(S)-γ-(arylamino)prolyl]-(S)-2-cyanopyrrolidine compounds on which we reported previously has a highly potent inhibitory activity but seemed to be unstable in neutral aqueous solution. Here, we describe [(S)-γ-(arylamino)prolyl]thiazolidine compounds as a novel series of potent and stable DPP-IV inhibitors. They are the thiazolidine analogs of [(S)-γ-(arylamino)prolyl]-(S)-2-cyanopyrrolidine but with the electrophilic nitrile removed to improve chemical stability in aqueous solution. Of the compounds investigated in the present study, the [((S)-γ-3,4-dicyanophenylamino)prolyl]thiazolidine 12m was the most potent. The structure-activity relationship (SAR) of the γ-substituent in the proline moiety of the thiazolidide was similar to that obtained with the (S)-2-cyanopyrrolidide. The γ-substituent in the proline moiety of both the (S)-2-cyanopyrrolidide and the thiazolidide may engage with the S2 binding pocket of DPP-IV and thereby achieve hydrophobic interaction in the same manner. Based on pharmacokinetic experiments in rats, the representative compound 11, which displayed high oral bioavailability (BA = 83.9%) and long half-life in plasma (t1/2 = 5.27 h), was found to have an excellent pharmacokinetic profile.

Pharmaceutical compositions as inhibitors of dipeptidyl peptidase-IV (DPP-IV)

The present invention relates to compounds of formula (I), which inhibit dipeptidyl peptidase IV (DPP-IV) and are useful for the prevention or treatment of diabetes, especially type II diabetes, as well as hyperglycemia, syndrome X, hyperinsulinemia, obesity, atherosclerosis, and various immunomodulatory diseases.

PHARMACEUTICAL COMPOSITIONS AS INHIBITORS OF DIPEPTIDYL PEPTIDASE-IV (DPP-IV)

The present invention relates to compounds of formula (I), which inhibit dipeptidyl peptidase IV (DPP-IV) and are useful for the prevention or treatment of diabetes, especially type II diabetes, as well as hyperglycemia, syndrome X, hyperinsulinemia, obesity, atherosclerosis, and various immunomodulatory diseases.

THIAZOLIDINE DERIVATIVE AND MEDICINAL USE THEREOF

A thiazolidine derivative represented by the formula (I) wherein each symbol is as defined in the specification, and a pharmaceutically acceptable salt thereof exhibit a potent DPP-IV inhibitory activity, and can be provided as an agent for the prophylaxis or treatment of diabetes, an agent for the prophylaxis or treatment of obesity and the like.

PROLINE DERIVATIVES AND USE THEREOF AS DRUGS

The present invention aims at providing compounds having therapeutic effects due to a DPP-IV inhibitory action, and satisfactory as pharmaceutical products. The present inventors have found that derivatives having a substituent introduced into the γ-position of proline represented by the formula (I) wherein each symbol is as defined in the specification, have a potent DPP-IV inhibitory activity, and completed the present invention by increasing the stability.