(2R)-3-Cyclopentyl-2-[4-(methanesulfonyl)phenyl]-N-(thiazol-2-yl)propionamide Chemical Properties

Density 

1.306

storage temp. 

Store at -20°C

solubility 

DMSO : 50 mg/mL (132.10 mM; Need ultrasonic)

form 

Powder

pka

8.65±0.50(Predicted)

color 

White to off-white

InChI

1S/C18H22N2O3S2/c1-25(22,23)15-8-6-14(7-9-15)16(12-13-4-2-3-5-13)17(21)20-18-19-10-11-24-18/h6-11,13,16H,2-5,12H2,1H3,(H,19,20,21)/t16-/m1/s1

InChIKey

NEQSWPCDHDQINX-MRXNPFEDSA-N

SMILES

[S](=O)(=O)(C)c1ccc(cc1)[C@@H](CC3CCCC3)C(=O)Nc2[s]ccn2

Safety Information

WGK Germany 

WGK 3

Storage Class

11 - Combustible Solids

(2R)-3-Cyclopentyl-2-[4-(methanesulfonyl)phenyl]-N-(thiazol-2-yl)propionamide Usage And Synthesis

Uses

A cell-permeable thiazolyl-propanamide compound that acts as an allosteric glucokinase-(GK) selective activator, increasing V_max and decreasing [S]_1/2 (by 1.5- and 4.3-fold, respectively, at 3 µM; [Glucose] = 5 mM) in human GK enzymatic assays, as well as freeing GK from the inhibitory action of GK regulatory protein (GKRP), resulting in increased GK nuclear-to-cytosol translocation in primary rat hepatocytes (EC₅₀/[Glucose] = 0.16 µM/16.8 mM, 0.27 µM/8.4 mM, 2.2 µM/2.8 mM) and reduced glucose concentration for stimulating insulin secretion from isolated rat pancreatic islets (threshold [glucose] = 3 mM vs 6 mM with or without 3 µM Ro-28-1675). Exhibits in vivo glucose-lowering and insulin-releasing activity in non-diabetic C57BL/6 mice and Wistar rats and is efficacious in several murine (KK/Upj-Ay/J, ob/ob, and diet-induced obese C57BL/6) and rodent (Goto-Kakizaki) type II diabetes mellitus (T2DM) models (10 to 50 mg/kg via p.o.), while efficacy is no longer observed in older hypoinsulinemic db/db mice with blood glucose levels reaching 300 mg/dl. Reported not to affect the activity of hexokinase I or II and display no activity toward GK-independent insulin release from β cells upon 2-Ketoisocaproic acid (α-KIC) stimulation.

Definition

ChEBI: (2R)-3-cyclopentyl-2-(4-methylsulfonylphenyl)-N-(2-thiazolyl)propanamide is a member of acetamides.

Biological Activity

RO-28-1675 is a potent allosteric activator of glucokinase with EC50 of 54 nM. It can be used in type 2 diabetes research.

in vitro