401564-30-5

Basic information

• Product Name: (2S,4R)-4-Hydroxy-2-(3-thiazolidinylcarbonyl)-1-pyrrolidinecarboxylic acid tert-butyl ester
• Synonyms: (2S,4R)-4-Hydroxy-2-(3-thiazolidinylcarbonyl)-1-pyrrolidinecarboxylic acid tert-butyl ester;1-Pyrrolidinecarboxylic acid, 4-hydroxy-2-(3-thiazolidinylcarbonyl)-, 1,1-diMethylethyl ester, (2S,4R)-
• CAS NO: 401564-30-5
• Molecular Formula: C₁₃H₂₂N₂O₄S
• Molecular Weight: 302.38978
• Mol File: 401564-30-5.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 492℃
• Flash Point: 251℃
• Appearance: /
• Density: 1.311
• CAS DataBase Reference: (2S,4R)-4-Hydroxy-2-(3-thiazolidinylcarbonyl)-1-pyrrolidinecarboxylic acid tert-butyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: (2S,4R)-4-Hydroxy-2-(3-thiazolidinylcarbonyl)-1-pyrrolidinecarboxylic acid tert-butyl ester(401564-30-5)
• EPA Substance Registry System: (2S,4R)-4-Hydroxy-2-(3-thiazolidinylcarbonyl)-1-pyrrolidinecarboxylic acid tert-butyl ester(401564-30-5)

Safety Data

• Hazardous Substances Data: 401564-30-5(Hazardous Substances Data)

Usage

General Description

The chemical (2S,4R)-4-Hydroxy-2-(3-thiazolidinylcarbonyl)-1-pyrrolidinecarboxylic acid tert-butyl ester, also known as Pioglitazone tert-butyl ester, is a derivative of Pioglitazone, a medication used to treat type 2 diabetes. The compound is a thiazolidinedione with antidiabetic properties, as it helps lower blood sugar levels by increasing the sensitivity of the body's cells to insulin. This particular compound is in the form of a tert-butyl ester, which is a common method of protecting chemically reactive functional groups in a molecule. It is used in medicinal chemistry research and drug development as a precursor for the synthesis of Pioglitazone and related compounds with potential therapeutic applications in diabetes and metabolic disorders.

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 articles and documents

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-(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.