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872998-61-3

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Evaluation of quinazoline analogues as glucocerebrosidase inhibitors with chaperone activity
Gaucher disease is a lysosomal storage disorder (LSD) caused by deficiency in the enzyme glucocerebrosidase (GC). Small molecule chaperones of protein folding and translocation have been proposed as a promising therapeutic approach to this LSD. Most small molecule chaperones described in the literature contain an iminosugar scaffold. Here we present the discovery and evaluation of a new series of GC inhibitors with a quinazoline core. We demonstrate that this series can improve the translocation of GC to the lysosome in patient-derived cells. To optimize this chemical series, systematic synthetic modifications were performed and the SAR was evaluated and compared using three different readouts of compound activity: enzymatic inhibition, enzyme thermostabilization, and lysosomal translocation of GC.
Marugan, Juan J.,Zheng, Wei,Motabar, Omid,Southall, Noel,Goldin, Ehud,Westbroek, Wendy,Stubblefield, Barbara K.,Sidransky, Ellen,Aungst, Ronald A.,Lea, Wendy A.,Simeonov, Anton,Leister, William,Austin, Christopher P.
experimental part
p. 1033 - 1058
(2011/04/25)

Total synthesis of luotonin and a small library of AB-ring substituted analogues by cascade radical annulation of isonitriles
A four-step total synthesis of luotonin is deployed to make a small library of AB-ring substituted analogues. These analogues show weak activity in a standard topoisomerase I mediated DNA cleavage assay. Georg Thieme Verlag Stuttgart.
Tangirala, Raghuraman,Antony, Smitha,Agama, Keli,Pommier, Yves,Curran, Dennis P.
p. 2843 - 2846
(2007/10/03)

More Articles about upstream products of 872998-61-3

86-96-4
1,2,3,4-tetrahydro-quinazoline-2,4-dione

More Articles about downstream products of 872998-61-3

Chemical Properties

Boiling Point: 406.583 °C at 760 mmHg
Flash Point:199.695 °C
Density: 2.023g/cm³
Storage Temp.:under inert gas (nitrogen or Argon) at 2-8°C
Vapor Pressure: 0mmHg at 25°C
Refractive Index: 1.71
PKA: -0.46±0.30(Predicted)
PSA: 25.78000
LogP: 3.15480

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