Synthesis and structure activity relationships of novel small molecule cathepsin D inhibitors

Human cathepsin D.

“…1,2-epoksy3-(p-nitrofenyloksy)-propan reacting with Asp33 [103] and methyl ester of diacetylo-DL-norleucine reacting with Asp231 are the synthetic inhibitors of cathepsin D [104]. Cathepsin D inhibitors, called pepstatins, are synthesized by bacteria of the genus Streptomyces [105][106][107]. Polypeptide inhibitors of this proteinase occur in spare organs of many plants [108] and in tissues of some lower ani- mals [109,110].…”

Biological Activities of 2-Mercaptobenzothiazole Derivatives: A Review

“…Impressed by these facts, MBT analogues 50 (Figure 27) were synthesized and screened as a cathepsin D inhibitor [123]. It was observed that the heteroatom linker between the two rings can be either sulfur or oxygen, while substitution of the middle ring resulted in a slight increase in activity when a lipophilic substituent (chlorine, methyl, trifluoromethyl) is added ortho to the heteroatom linker.…”

Copper‐Catalyzed Domino Synthesis of Sulfur‐Containing Heterocycles Using Carbon Disulfide as a Building Block

“…[3] However, the methods available for CÀ S bond formation, especially in a domino process, are rather limited because of the propensity of thiols to undergo oxidative dimerization and their affinity for transition metals, resulting in a decrease in catalytic efficiency. [6] 2-Thio-substituted benzothiazoles are an important class of sulfur-containing compounds possessing various excellent medicinal and biological activities, [7] including heat shock protein-90 (HSP) inhibitor A, [8] Cathepsin-D inhibitor B, [9] avarol-3'-thiobenzothizole C, [10] and PPAR receptor activator D [11] (Figure 1a). [5] Thus, it is challenging and highly desirable to develop efficient methods for the formation of CÀ S bonds in a one-pot organic transformation, using a single catalyst to mediate two or more reactions.…”