Boutin, Sophie; Maltais, Rene; Roy, Jenny; Poirier, Donald published the artcile< Synthesis of 17β-hydroxysteroid dehydrogenase type 10 steroidal inhibitors: Selectivity, metabolic stability and enhanced potency>, Application In Synthesis of 56724-03-9, the main research area is androstane D ring derivative preparation HSD10 inhibitor; 17β-HSD10; Alzheimer disease; Enzyme; Inhibitor; Solid-phase synthesis; Steroid.
17Beta-Hydroxysteroid dehydrogenase type 10 (17β-HSD10) is the only mitochondrial member of 17β-HSD family. This enzyme can oxidize estradiol (E2) into estrone (E1), thus reducing concentration of this neuroprotective steroid. Since 17β-HSD10 possesses properties that suggest a possible role in Alzheimer’s disease, its inhibition appears to be a therapeutic strategy. After we identified the androsterone (ADT) derivative I as a first steroidal inhibitor of 17β-HSD10, new analogs were synthesized to increase the metabolic stability, to improve the selectivity of inhibition over 17β-HSD3 and to optimize the inhibitory potency. From six D-ring derivatives of I (17-C=O), two compounds (17β-H/17α-OH and 17β-OH/17α-CCH) were more metabolically stable and did not inhibit the 17β-HSD3. Moreover, solid phase synthesis was used to extend the mol. diversity on the 3β-piperazinylmethyl group of the steroid base core. Eight over 120 new derivatives were more potent inhibitors than I for the transformation of E2 to E1, with the 4-(4-trifluoromethyl-3-methoxybenzyl)piperazin-1-ylmethyl-ADT (D-3,7) being 16 times more potent (IC50 = 0.14μM). Finally, D-ring modification of D-3,7 provided 17β-OH/17α-CCH derivative and 17β-H/17α-OH derivative, which were more potent inhibitor than I (1.8 and 2.4 times, resp.).
European Journal of Medicinal Chemistry published new progress about Alzheimer disease. 56724-03-9 belongs to class ethers-buliding-blocks, and the molecular formula is C9H10O2, Application In Synthesis of 56724-03-9.
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem