393791-87-2

Upstream product

• 124-63-0 methanesulfonyl chloride 
• 337307-10-5 (2S,4R)-2-Hydroxymethyl-4-tritylsulfanyl-pyrrolidine-1-carboxylic acid tert-butyl ester 
• 121147-93-1 (2S,4S)-2-methyl N-Boc-4-((methylsulfonyl)oxy)pyrrolidine-2-carboxylate 
• 74844-91-0 (2S,4S)-N-tert-butoxycarbonyl-4-hydroxyproline methyl ester 
• 169032-99-9 (2S,4S)-4-Chloro-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester 
• 176306-17-5 (2S,4R)-4-tritylsulfanylpyrrolidine-1,2-dicarboxylic acid 1-tert-butyl-2-methyl diester 
• 74844-91-0 1-tert-butyl 2-methyl (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate 

Downstream Products

• 393792-04-6 (2S,4R)-2-azidomethyl-4-tritylsulfanylpyrrolidine 
• 844476-72-8 (2S,4R)-2-azidomethyl-4-tritylsulfanylpyrrolidine-1-carboxylic acid isopropyl ester 
• 844476-73-9 (2S,4R)-2-aminomethyl-4-tritylsulfanylpyrrolidine-1-carboxylic acid isopropyl ester 
• 844476-74-0 (2S,4R)-2-[(2,5-difluorobenzylamino)methyl]-4-tritylsulfanylpyrrolidine-1-carboxylic acid isopropyl ester 
• 341973-06-6 Pyrrophenone 
• 337307-12-7 ((2S,4R)-2-Azidomethyl-4-tritylsulfanyl-pyrrolidin-1-yl)-[2-(2,4-difluoro-benzoyl)-phenyl]-methanone 
• 337307-11-6 (2S,4R)-2-azidomethyl-4-tritylsulfanylpyrrolidine-1-carboxylic acid tert-butyl ester 

Relevant academic research and scientific papers

Endothelin-converting enzyme-1 inhibition and growth of human glioblastoma cells

Endothelin-1 (ET-1) is mitogenic and/or antiapoptotic in human cancers, and antagonists to ET-1 receptors are under evaluation for cancer treatment. Inhibition of ET-1 activation by the endothelin-converting enzymes 1 a-d (ECE-1a-d; EC 3.4.24.71) represents another approach to block the ET-1 effect in cancer. To evaluate this potential, we synthesized and characterized a series of low nanomolar nonpeptidic thiol-containing ECE-1 inhibitors, and evaluated their effect, as well as the effect of inhibitors for the related metalloproteases neprilysin (NEP; EC 3.4.24.11) and angiotensin-converting enzyme (ACE; EC 3.4.15.1), on human glioblastoma cell growth. Only ECE-1 inhibitors inhibited DNA synthesis by human glioblastoma cells. Exogenous addition of ET-1 or bigET-1 to glioblastoma cells did not counterbalance the growth inhibition elicited by ECE-1 inhibitors, suggesting that ECE-1 inhibitors block the proliferation of human glioblastoma cells most likely via a mechanism not involving extracellular production of ET-1. This class of molecules may thus represent novel therapeutic agents for the potential treatment of human cancer.

Pyrrolidine inhibitors of human cytosolic phospholipase A2. Part 2: Synthesis of potent and crystallized 4-triphenylmethylthio derivative 'pyrrophenone'

We synthesized a potent and crystallized human cytosolic phospholipase A2α inhibitor, pyrrophenone (6) which inhibits the isolated enzyme with an IC50 value of 4.2 nM. Pyrrophenone shows potent inhibition of arachidonic acid release, prostaglandin E2, thromboxane B2, and leukotriene B4 formation in human whole blood. The magnitudes of prostaglandin E2 and thromboxane B2 inhibition are the same as those of indomethacin.