1201580-99-5

Upstream product

• 59378-81-3 1-(tert-butoxycarbonyl)prolin-2R-ol 
• 43041-12-9 methyl (2R)-pyrrolidine-2-carboxylate 
• 28732-79-8 4-chloro-pyrido[2,3-d]pyrimidine 
• 924907-34-6 (R)-2-(2-chlorophenoxymethyl)pyrrolidine 
• 344-25-2 D-Prolin 

Relevant academic research and scientific papers

Novel reversible methionine aminopeptidase-2 (MetAP-2) inhibitors based on purine and related bicyclic templates

The natural product fumagillin 1 and derivatives like TNP-470 2 or beloranib 3 bind to methionine aminopeptidase 2 (MetAP-2) irreversibly. This enzyme is critical for protein maturation and plays a key role in angiogenesis. In this paper we describe the synthesis, MetAP-2 binding affinity and structural analysis of reversible MetAP-2 inhibitors. Optimization of enzymatic activity of screening hit 10 (IC50: 1?μM) led to the most potent compound 27 (IC50: 0.038?μM), with a concomitant improvement in LLE from 2.1 to 4.2. Structural analysis of these MetAP-2 inhibitors revealed an unprecedented conformation of the His339 side-chain imidazole ring being co-planar sandwiched between the imidazole of His331 and the aryl-ether moiety, which is bound to the purine scaffold. Systematic alteration and reduction of H-bonding capability of this metal binding moiety induced an unexpected 180° flip for the triazolo[1,5-a]pyrimdine bicyclic template.

Novel pyrrolidone derivatives for use as MetAP-2 inhibitors

Compounds of the formula (I), in which R, X, Y, Z, R3 and R4 have the meanings indicated in claim 1, are inhibitors of methionine aminopeptidase and can be employed for the treatment of tumours.