274918-46-6Relevant articles and documents
ALIPHATIC PROLINAMIDE DERIVATIVES
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, (2018/04/11)
This invention is directed to novel aliphatic prolinamide derivatives of Formula I, and pharmaceutically acceptable salts, solvates, solvates of the salt and prodrugs thereof, useful in the prevention (e.g., delaying the onset of or reducing the risk of developing) and treatment (e.g., controlling, alleviating, or slowing the progression of) of age-related macular degeneration (AMD) and related diseases of the eye. These diseases include dry-AMD, wet-AMD, geographic atrophy, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, and degeneration of retinal or photoreceptor cells. The invention disclosed herein is further directed to methods of prevention, slowing the progress of, and treatment of dry-AMD, wet-AMD, and geographic atrophy, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, and degeneration of retinal or photoreceptor cells, comprising: administration of a therapeutically effective amount of compound of the invention. The compounds of the invention are inhibitors of HTRAl. Thus, the compounds of the invention are useful in the prevention and treatment of a wide range of diseases mediated (in whole or in part) by HTRAl. The compounds of the invention are also useful for inhibiting HTRAl protease activity in an eye or locus of an arthritis or related condition.
Conformationally constrained analogues of bleomycin A5
Rishel, Michael J.,Thomas, Craig J.,Tao, Zhi-Fu,Vialas, Corine,Leitheiser, Christopher J.,Hecht, Sidney M.
, p. 10194 - 10205 (2007/10/03)
The bleomycin (BLM) group antitumor antibiotics are glycopeptide-derived natural products shown to cause sequence selective lesions in DNA. Prior studies have indicated that the linker region, composed of the methylvalerate and threonine residues, may be responsible for a conformational bend in the agent required for efficient DNA cleavage. We have synthesized a number of conformationally constrained methylvalerate analogues and incorporated them into deglycobleomycin A5 congeners using our recently reported procedure for the solid phase construction of (deglyco)bleomycin and its analogues. These analogues were designed to probe the effects of conformational constraint of the native valerate moiety. Initial experiments indicated that the constrained molecules, none of which mimic the conformation proposed for the natural valerate linker, possessed DNA cleavage activity, albeit with potencies less than that of (deglyco)BLM and lacking sequence selectivity. Further experiments demonstrated that these analogues failed to produce alkali-labile lesions in DNA or sequence selective oxidative damage in RNA. However, two of the conformationally constrained deglycoBLM analogues were shown to mediate RNA cleavage in the absence of added Fe2+. The ability of the analogues to mediate the oxygenation of small molecules was also assayed, and it was shown that they were as competent in the transfer of oxygen to low molecular weight substrates as the parent compound.
α-Ketoamides, α-ketoesters and α-diketones as HCV NS3 protease inhibitors
Han, Wei,Hu, Zilun,Jiang, Xiangjun,Decicco, Carl P.
, p. 711 - 713 (2007/10/03)
Peptide-based α-ketoamides, α-ketoesters and α-diketones were designed, synthesized and evaluated against HCV NS3 protease. α-Ketoamides have the highest affinity among the three classes, with 8 being the most potent inhibitor with an IC50 of 3
